SABIN VACCINE REPORT the newsletter of the Albert B. Sabin Vaccine Institute Volume III, Number 1, May 2000

In This Issue Gates Foundation Awards $18 Million to Sabin Institute Funds Awarded for Development of Hookworm Vaccine

The Hookworm Vaccine JOHN M. CLYMER will draw on expertise and resources from each Initiative Unfolds sector to translate scientific knowledge about he Albert B. Sabin Vaccine Institute has hookworm antigens into a International disease burden real product that helps “This grant from the necessitates vaccine received an $18 million grant from the Bill development. T & Melinda Gates Foundation. The funds will people lead healthier lives, he Bill & Melinda Gates be used for the development of a vaccine to prevent said. Foundation 6,7 hookworm infection. Approximately one-quarter of “We are proud to represents the world’s population is infected with hookworm. support the Albert B. Sabin enlightened The Search for an AIDS “This grant from the Bill & Melinda Gates Vaccine Institute and its philanthropy because Vaccine Foundation represents enlightened philanthropy quest to find a hookworm it will help us over Gary Nabel gives AIDS because it will help us over the major economic vaccine, which will free the major economic Vaccine Research a Face. barriers that have prevented development of a millions of the world’s most barriers that have hookworm vaccine,” said H. R. “Shep” Shepherd, economically disadvantaged prevented 4,5 chairman of the people development of a from this hookworm China Confronts her AIDS Sabin Vaccine Epidemic. Institute. disease,” vaccine...” “This is a huge said 5 step toward Gordon W. Perkin, M.D., democratizing director of the Global Health UNICEF and Rotary healthcare Program at the Bill & Melinda Intensify Polio throughout the Gates Foundation. Eradication Efforts. world,” said The Sabin Vaccine Public and private sectors Shepherd. Institute’s mission is to save lives partner to free the world of “Hookworms infect by stimulating development of polio by 2003. about one billion new vaccines and by increasing people, mostly in immunization rates. It was 8 developing countries. founded in 1993 and named for SmithKline Beecham They stunt children’s Albert B. Sabin, developer of the introduces a new growth, sap oral polio vaccine that has been victims’ energy at the heart of the nearly-

combination vaccine. photo compliments of MHL and make them Dr. Peter Hotez visits children at a health clinic in Beijing. complete worldwide effort to Pentavalent vaccine joins the eradicate paralytic polio. This is ranks of common combination anemic. A vaccines like DPT and MMR. vaccine is the only realistic way to protect all people the Institute’s first research and development from this parasite.” program. Other Institute programs bring scientists 3 Peter J. Hotez, called “one of the world’s few together to share cutting-edge ideas and data to hookworm experts,” in a 1998 Washington Post accelerate vaccine development, and advocate Cancer Vaccine article, will be the principal scientist directing the sound immunization strategies to combat disease. Researchers Making project. He is a member of the Institute’s council of The Bill & Melinda Gates Foundation is Advances. scientific advisors. dedicated to improving people’s lives by sharing 11 “Hookworm is a particularly serious problem advances in health and learning with the global in rural China. In some villages, more than one half community. Led Experts Recommend New of the population is infected,” Hotez said. He by Bill Gates’ “Chronic hookworm-associated Flu Vaccine frequently visits remote areas father, William H. intestinal blood loss leads to 3 “Hookworm is a of China to conduct research Gates, Sr., and iron deficiency and protein particularly serious as a visiting professor at the Patty Stonesifer, malnutrition. These conditions BOOK REVIEW: The Politics of problem in rural Chinese Academy of the Seattle-based often retard intellectual and International Health China. In some Preventive Medicine’s Foundation has physical growth...” 10 villages, more than Institute of Parasitic Disease an asset base of one half of the and the Peking Union Medical approximately SVI Chairman advocates population is College. The parasite is $21.8 billion. Preventing disease among poor vaccine use. infected,” Hotez estimated to be similarly children by expanding access to vaccines, and 12 said. prevalent in India, and is a developing vaccines against malaria, HIV/AIDS and major health problem in tuberculosis, are central priorities. Other major certain Latin American countries, as well. efforts include extending unprecedented “Hookworms infect people of all ages but they opportunities for learning by bringing computers with are particularly devastating in children,” explained Internet access to every eligible public library in the Hotez. “Chronic hookworm-associated intestinal U.S. and Canada, and providing scholarships to blood loss leads to iron deficiency and protein academically talented minority students with severe malnutrition. These conditions often retard financial need through the Gates Millennium Scholars intellectual and physical growth,” according to Program. v Hotez. People who are treated for hookworm tend to become reinfected, he added. John Clymer is director of external affairs for the Albert No single sector – academia, government, B. Sabin Vaccine Institute. industry or philanthripy – can develop a vaccine alone, Shepherd noted. The Sabin Vaccine Institute For complete information and grant guidelines visit

Sabin Vaccine Report Sabin Vaccine Institute Albert B. Sabin Vaccine 58 Pine Street New Canaan, CT 06840 www.gatesfoundation.org. 2SABIN VACCINE REPORT February 2000 Doubting Vaccines Is Dangerous Business In the 1790s, from the disease. By 1998 there were only Too often, these deaths occur because people receiving 1,000 diagnosed cases and none of those other countries’ restrictive or bureaucratic the world’s first cases were fatal. In 1968, there were more policies make vaccines unavailable to their vaccine - the than 150,000 cases of mumps in the U.S. but citizens. The United States works hard to help smallpox vaccine - by 1993, there were remedy this problem, but if our own citizens were convinced just over 11, 500. begin to doubt vaccines, we could initiate a they would take on Vaccines have Today, every dollar dangerous chain reaction around the world. the physical reduced infection spent on vaccines And if the number of unvaccinated children characteristics of and death from the flu saves $27 in begins to grow, the worldwide benefits of the cows that were by 54%. And thanks treatment. immunization will rapidly erode - causing photo by Beth Shepherd Peters used to create the to vaccines, there preventable illnesses to proliferate globally. H. R. Shepherd, medicine. Today has not been a single case of polio in the This has already happened in the past. Chairman of the Sabin we know their United States since 1975. Cholera, typhoid, In the 1970s, rumors associated with a Vaccine Institute fears were German measles, whooping cough and pertussis vaccine lead to a drop in vaccination unfounded; in fact, smallpox has now been diphtheria are only a sampling of the diseases rates in several countries and a consequent eradicated. Yet after two centuries of success that vaccines currently control in the U.S. rise in the against a host of crippling and fatal diseases, In all, vaccines have protected countless prevalence of Every year in the United vaccines are under attack from unwarranted millions of lives - including yours and mine - the disease. States, approximately 70,000 fears once again. from once-common killers. The fact is We must not people - including 500 Recent television, print and radio news vaccines are one of the safest and most make the same children - die unnecessarily stories in the United States, along with a effective medical interventions of our time. mistake again. from diseases that could growing number of Internet sites, are claiming Moreover, they are one of the most As we have been prevented by vaccines are economical; today, every dollar spent on enter the 21st existing vaccines. “Nothing is more dangerous or even vaccines saves $27 in treatment. century, dangerous than fatal. In response to Unfortunately, the very success of vaccines are ignorance in action.” rumors that vaccines vaccines has caused a dangerous outbreak of poised to play an increasingly central role in are the catalysts of complacency and misunderstanding. Many of our future, saving millions of lives each year such wide-ranging today’s young parents have never while dramatically cutting health care costs. disorders as autism, asthma and diabetes, encountered the diseases their children’s On the near horizon, a new vaccine awaiting some parents have begun questioning the inoculations prevent and consequently believe FDA approval promises to protect children from wisdom of vaccinating their children. These these horrors couldn’t possibly return. pneumonia and meningitis. And in the years to fears are both strange and perilous. They are Meanwhile, preventable killers such as come, vaccines could conquer some of our based not on reality or scientific evidence but measles, pertussis (whooping cough) and century’s worst scourges - malaria, dysentery, on ignorance and, in many cases, the need to hepatitis B lurk patiently in the shadows - AIDS and even some cancers. However, a find a medical scapegoat when the poised to make a widespread comeback misinformed public outcry could delay this unexplainable occurs. Those who allow should immunizations decline. exciting progress and cost countless lives. themselves to be ruled by these baseless If we are to keep infectious diseases at Despite early fears, vaccines never did misconceptions risk undermining one of bay, we must eliminate the notion that they no endow people with the qualities of cows. Let humankind’s greatest medical resources. As longer pose a serious threat. Every year in the us not be cowed today by the latest crop of Goethe warned, “Nothing is more dangerous United States, approximately 70,000 people vaccine myths. We must spread the facts - not than ignorance in action.” - including 500 children - die unnecessarily ignorance - so that humankind will continue to In this case, ignorance could bring from diseases that could have been prevented enjoy the benefits of our greatest medical miracle. irreparable harm to us all. by existing vaccines. That’s one person every v Before the development of a measles eight minutes. Throughout the world, millions H. R. Shepherd is Chairman of the Albert B. Sabin vaccine in the 1960s, there were some of people die annually from vaccine- Vaccine Institute. 500,000 cases each year, and thousands died preventable diseases.

The Sabin Vaccine Report is published by the EDITOR SABIN VACCINE INSTITUTE STAFF Albert B. Sabin Vaccine Institute. Charlene A. Flash H. R. Shepherd, Chairman Subscriptions are free. ASSISTANT EDITOR Veronica Korn Fran Sonkin, Executive Vice President Philip K. Russell, Special Advisor to the Chairman Please direct inquiries to: WRITERS/STAFF Peter J. Hotez, Chair Scientific Advisory Board John Clymer SABIN VACCINE REPORT Lea Gill, Aide to Chairman Nishiena Ghandi 58 Pine Street Gboku Lumbila John M. Clymer, Director External Relations New Canaan, CT 06840 Jessica Quinn Valerie Manda, Visiting Postdoctoral Fellow phone: 203.972.7907 Charlene A. Flash, Research Fellow facsimile: 203.966.4763 COPY EDITOR email: [email protected] Daphna Gregg Veronica Korn, Research Associate Gboku Lumbila, Executive Assistant CONTRIBUTORS The Albert B. Sabin Vaccine Institute is a Peter J. Hotez, MD PhD non-profit institute dedicated to continuing H. R. Shepherd the work and achieving the vision of Albert John Shao, PhD B. Sabin: to fully realize the potential of Myrna Watanabe, PhD vaccination to prevent disease. Patricia Thomas Founded in 1994, the Institute strives to prevent disease by promoting the Dedicated to Disease Prevention development of new vaccines and delivery www.sabin.org systems. SABIN VACCINE REPORT February 2000 3 Combination Vaccines Minimize Pain; Save Money BY VERONICA KORN spokesperson Carmel Hogan during a telephonic such as staffing issues in clinics and basic poverty nfant immunization schedules requiring several interview recently, said that should the FDA often prevent the population from receiving vaccines. inoculations during each doctor’s visit may approve this vaccine, it would be the first Preliminary randomized studies on over Ibecome a thing of the past as more pentavalent vaccine licensed in the country. The 7,000 children in the U.S. for a total of 20,000 combination vaccines are developed and company already has had success with other worldwide show the combination vaccine to be approved. A combined vaccine will have far- combination vaccines such as Twinrix, for as safe, efficacious and immunogenic as the reaching affects for global immunization Hepatitis A and Hepatitis B, as well as Infantrix, monovalent vaccines. Although combination campaigns particularly in developing nations. The the DTaP inoculation, which the FDA approved vaccines such as the SKB pentavalent require availability of a combined vaccine—a vaccine in 1997. Hogan said the success of these just one inoculation per visit, the pentavalent produced from cultures of a number of vaccines has largely led to a greater concentration vaccine would still be repeated on the childhood organisms—simplifies the actual implementation within SB on combination vaccine development. immunization schedule at two, four and six months of inoculations, by enabling a single injection for Valerie Manda, a medical microbiologist of age, said Hogan. application of multiple vaccines. Combination from the Medical University of South Africa When asked about individual vaccines and vaccines minimize pain and discomfort, cost and (MEDUNSA) in Pretoria, South Africa the future of companies who manufacture them, time; and would maximize successful immunization Combination vaccines will increase comliance Hogan said those vaccines will still be needed as programs by increasing compliance. because they will minimize multiple shots. booster, or supplemental, shots for both children The DTP (diphtheria pertussis polio “Combination vaccines will increase comliance and adults. SB has other combination vaccines vaccine) was among the first of such because they will minimize multiple shots. It’s in Phase three of development (see fig.1). These combination vaccines, being developed in good for technology to go ahead...progress, but include an MMR-Varicella, measles, mumps, 1943, and licensed for use in the US in 1948. basic problems still need to be conquered.” rubella and chicken pox in phase IIIa and hepatitis This and others are commonly used in doctors’ Amongst these problems, Manda cited A + Salmonella typhi in phase IIIb. v accesibility to vaccines and vaccination clinics. offices and hospitals, namely the MMR Veronica Korn is a Research Associate at the Sabin In poorer countries, she noted, simple situations vaccine against measles, mumps and rubella Vaccine Institute. (manufactured by Merck), and the DTaP vaccine against diphtheria, tetanus and OTHER COMBINATION VACCINES pertussis (multiple manufacturers). Currently, North American Vaccines and Wyeth Vaccines and Nutrition are concentrating on further increasing the coverage in combination Twinrix Hepatitis A+B SmithKline Beecham Marketed vaccinations to protect against up to five, rather than the standard three, childhood Brand Combination Company Stage diseases at once. Tetracel Diptheria,Tetanus, Wyeth-Lederle Phase II In July 1999, SmithKline Beecham (SB) Pertussis,Hib Disease (American Home Products) submitted a license application to the United States Food and Drug Administration (FDA) for Certiva Diptheria and Tetanis Toxoids, North American Vaccines Marketed a new combination vaccine against diphtheria, Acellular Pertussis Vaccine Absorbed tetanus, pertussis, hepatitis B and polio. While the much used DTaP combined vaccine has existed for some time, the SmithKline product, Unnamed MMR+Varicella SmithKline Beecham Phase III called InfantrixDTaPaÒHepB-IPV, would now protect against five major childhood diseases and reduce the number of shots required for effective SOURCE: SmithKline Beecham PLC, American Hompe Products, North American Vaccines immunization from nine to three. U.S. SmithKline

Experts Recommend New Flu Vaccine For Next Season

BY JESSICA QUINN hundred and twenty-two cities contribute to the that will counter the strains circulated this he rising temperatures and blooming MRS data, reporting the number of deaths winter. The influenza viruses infecting humans flowers not only signal the beginning of attributed to influenza or pneumonia. Both and animals are isolated and studied. WHO Tspring, but also the end of the flu MRS and the State and Territorial Collaborating Centers then sequence and season. Very early this season between Epidemiologists Report are part of the Centers identify the categories of the viruses. Each December 25, 1999 and January 15, 2000, for Disease Control’s (CDC) influenza February the results are discussed in Geneva many people contracted the flu. This early surveillance system. By this system the CDC and a recommendation for the composition of peak in the season sent many scrambling to aims to determine the strains of flu viruses the next season’s vaccine is made by the get flu shots for fear this was to be the worst circulating and monitors their effects on the WHO. The composition of the vaccine for the flu season yet. Statistics compiled by the United States population. Northern Hemisphere’s flu season (November Centers for Disease Control show, however, Last year’s flu season was marked by 2000- April 2001) has been determined and that this year was not much different than people who contracted the flu although they given to vaccine manufacturers by the World previous years. The flu vaccine effectively had already been vaccinated. Health experts Heath Organization (WHO). preempted what would have been the worst cannot determine whether the strain has grown In the Unites States a panel of experts, flu season yet. “Epidemic” flu rates and less effective or whether they received more or Federal Health Advisors, reviewed the hospital visits linked to the flu were fairly samples of this population than usual. WHO findings and recommended a change to comparable to the last five seasons. According to the FDA, each Fall between 60 the formula for next season’s flu vaccine. In According to the CDC, deaths from and 80 million Americans receive the influenza March these experts advised the Federal Drug pneumonia or those directly linked to influenza vaccine. Health experts choose the formula Administration in the United States to replace were only up 2 percent to 11.2 % during the they believe will protect the most people from Type A strain vaccine with a new strain noted last few seasons. The flu season lasts from the most common type of the flu virus at least in Panama. The type A strain, common last flu October until February. one month prior to the distribution of shots. season, was first identified on the South Pacific Although the flu season is behind us, health According to the Mortality Reporting island of New Caledonia. v System (MRS), the highest percentage of officials continue to study the virus and its patient visits for influenza-like-illness (ILI) and effects. Work has already begun on developing Jessica Quinn is a Sophomore Biology major and patient deaths occurred in January. One next season’s vaccine for our next flu season English minor at Georgetown University. 4SABIN VACCINE REPORT February 2000 Gary Nabel: Vaccine Research Center Head Rises to Challenge BY PATRICIA THOMAS early 1998. Although he had shepherded new therapy into humans is no easy task. “I wrote n a muggy Sunday morning in experimental gene therapies from the lab to the the clinical protocol, I wrote the IRB (request to Baltimore, speaking at the clinic, and this work was central to him, he knew experiment on humans) and the FDA application, O graduation ceremony of Morgan State that these advances could help only a limited number we developed the production process, I went down University, President Clinton challenged science to of people. And here was Varmus talking about the for the IND (Investigational New Drug) meetings develop an AIDS vaccine within 10 years. To speed search for an AIDS vaccine, something that could with the FDA, I treated the first patient, I even wrote this globally important effort, he announced that a potentially save millions of lives throughout the world. the informed consent,” Nabel recalls, sounding glad major new AIDS It was a tantalizing prospect. to have done this but relieved that it’s over. “I saw Vaccine Research But Nabel could not say yes right away. His every aspect of what’s needed to bring something Center (VRC) would be wife, Elizabeth Nabel, is a well-known cardiologist forward into a clinical study, and I learned from that.” created at the National with her own laboratory and clinical duties at the This product is now being tested in a Phase III study Institutes of Health. “If University of Michigan, where Gary Nabel himself enrolling patients with advanced melanoma, and in a the 21st century is to be was director of the Center for Gene Therapy. They Phase I trial with head and neck cancer patients. the century of biology, let have juggled two careers ever since they met as us make an AIDS internal medicine residents at a Boston hospital, and Bridging the gaps vaccine its first great it was only after Elizabeth Nabel was offered a Although Nabel has never designed an HIV triumph,” the President position at NIH’s National Heart, Lung, and Blood vaccine, his lab is working on a vaccine for Ebola Photo compliments of the NIH. said to great applause. Institute that the Nabels and their children headed virus. More relevant to the VRC’s mission is his Gary Nabel directs the Few would have east. Nabel says that his favorite leisure activity is nation’s first AIDS “translational” experience with gene therapy. Nabel Vaccine Research guessed that nearly two being with his family, and he wanted everyone to hopes that the VRC will remove stumbling blocks Center. years would pass before be happy with the move. from the path of vaccine developers. Some vaccine Health and Human Although an article in Science described him efforts, for example, are stymied when their Services Secretary Donna Shalala officially as “a relative newcomer to AIDS vaccine work,” academic inventors don’t have the resources to make announced that physician-scientist Gary Nabel, Gary Nabel is hardly a stranger to HIV research or test batches. Other ideas languish in the labs of known primarily as a gene therapy researcher at to the ways of the NIH. Nabel went straight from corporate scientists, who must put all their energy the University of Michigan, would come on board Harvard College to a joint M.D.-Ph.D. program at into the company’s lead technology instead of to lead the VRC. Harvard Medical School. “I knew that I wanted to exploring new approaches. The long interval between the President’s do medicine, but I also wanted to do science,” he The VRC will enable vaccine scientists “to May 1997 announcement and Nabel’s hire recalled. “It was something I decided very early on.” see it through,” an opportunity that he hopes will in March of this year provided plenty of time He studied immunology in graduate school, lure new talent to the enterprise. Instead of for loose talk. Many vaccine researchers said completed an internal medicine training program in reorganizing long-time NIH personnel, Nabel has that the 10-year goal was overly optimistic; Boston, and in 1985 became a postdoctoral fellow the go-ahead to recruit about 100 full time others predicted that the VRC would be in David Baltimore’s virology lab at the Whitehead employees, including researchers and support staff. nothing more than a cosmetic reshuffling of Institute at the Massachusetts Institute of Technology. Completion of the Dale and Betty Bumpers Vaccine current NIH researchers and resources. There This postdoc put Nabel in the vortex of AIDS Research Center, honoring the former Senator from was no director in sight in August 1998, when research. Baltimore was not only a Nobel laureate, Arkansas and his wife is expected in August 2000, the NIH broke ground for the VRC, a five- the founding director of the Whitehead, and an expert and the facility will provide containment facilities for story building expected to cost $26-million. on HIV and other retroviruses, he was also in the handling dangerous organisms, a small GLP Top drug company executives and experienced innermost circle of the scientific establishment. In manufacturing facility for making test batches, and vaccinologists were said to have turned down 1986, for example, he chaired a blue-ribbon Institute a research group focused on developing assays for the job because the pay was too low, there of Medicine panel that assessed the overall state of clinical trials. These resources can be used to help were too many bosses and too little authority, AIDS research. His lab launched the careers of researchers elsewhere at NIH, in academia, or in or the whole idea was nothing more than an many outstanding young scientists, and Nabel was corporate settings. The point is to keep promising empty political gesture. among them. At the Whitehead, Nabel explored ideas from withering on the vine. Gary Nabel walked into this gossipy how HIV subverts the machinery of T-cells, town square with no visible signs of published impressive papers, and went to seek his defensiveness or distress. Whether he’s fortune in Ann Arbor. Research agenda evolving presiding over planning sessions, speaking at Nabel and his new scientific team will be large scientific meetings, or meeting with AIDS Gaining something in closely watched as they set their scientific priorities. advocates, he speaks his mind calmly and Nabel reports to an executive committee of top comes across as a solid, reasonable fellow. translation NIH administrators, including not only NIH director He’s a tall lean man of 46, losing hair earlier At Michigan, Nabel began to inject foreign Varmus but also Tony Fauci of the National Institute than he would like, with expressive hands that genetic material directly into human tumors, in hopes for Allergy and Infectious Disease and Richard he uses to underline his points. He listens of inducing the patient’s immune system to attack Klaussner of the National Cancer Institute. The closely to others and is quick to murmur assent the cancer. When preclinical studies showed VRC also answers to an intramural scientific board when he hears something he likes. promise, he arranged for Vical, a San Diego-based and to an external advisory committee that will biotech company, to package the genetic material probably be an offshoot of the AIDS Vaccine Dark horse from Michigan in tiny lipid beads called liposomes. (In the world of Research Committee. David Baltimore, Nabel’s HIV vaccines, Vical is better known for the DNA former mentor, chairs the AVRC. NIH Director Harold Varmus first vaccine technology it licensed to Merck.) Fortunately, Nabel is no stranger to the world approached Nabel about the VRC directorship in Nabel soon discovered that moving a radical of NIH committees. He was a member of the NIAID’s AIDS Research Advisory Committee from 1993 to 1997, and chaired the group during AIDS VACCINE RESEARCH ENTITIES OF THE his final year of service. In 1994, Nabel was among NATIONAL INSTITUTES OF HEALTH the majority of ARAC members who voted not to expand clinical testing of the recombinant gp120 vaccines owned by Chiron and Genentech (now NATIONAL CENTER OFFICE OF NATIONAL INSTITUTE OF VaxGen). Over the years he’s kept track of FOR RESEARCH AIDS ALLERGY AND INFECTIOUS candidate vaccines for HIV, and expects the VRC RESOURCES DISEASES (NIAID) RESEARCH to throw its early support behind combination DIVISION OF AIDS DIVISION OF AIDS strategies that appear to elicit both antibodies and CTL-activity. In the long run, Nabel expects good results from DNA vaccines or live vectors. SABIN VACCINE REPORT February 2000 5

China Holds First International HIV Nabel wants the VRC to play an active role in developing vaccines for the world, not just the Vaccine Workshop United States. Although there are clear genetic BY MYRNA E. WATANABE, PHD given by Shao at the meeting. The next group in differences among HIV subtypes from different which HIV was identified was intravenous (IV) parts of the globe, “it’s still an open question what n November 18-23, 1999, the National drug users in Yunnan Province who injected pure these differences mean in terms of immune Center for AIDS Prevention and heroin. Cases also were identified along China’s responses,” Nabel said, vowing that the VRC will OControl (NCAIDS), Chinese Academy coast and in its large cities. help back international clinical trials. Africa and other of Preventive Medicine, Ministry of Health, and Yunnan, in southwestern China, adjacent parts of the developing world are suffering mightily Ministry of Science and Technology of the to the Golden Triangle region of Myanmar from the AIDS pandemic, and the U.S. should People’s Republic of China hosted their first (formerly Burma), currently has the highest HIV support international trials mainly because “ it’s just International AIDS Vaccine Workshop. Nearly infection rate in the country. According to Hehe the right thing to do.” 40 foreign scientists and about 70 Chinese Cheng of the Yunnan Center for AIDS While the pursuit of a vaccine that can protect researchers, clinicians, government officials, Prevention, Care and Research in Kunming, millions against AIDS is the central mission of the graduate students, and post-doctoral students 89.3% of the people from Yunnan infected with VRC right now, “I hope that we’re going to be attended the workshop. The goals of the meeting HIV are IV drug users s. developing, as much as possible, a set of rules or were to introduce foreign HIV research to Molecular epidemiological evidence lessons that we can apply to other vaccines,” Nabel Chinese scientists, especially those unable to indicates that the infection spread in a said. There’s every reason to expect that new travel extensively, and to introduce the data China northeasterly direction into Sichuan Province, then epidemics are waiting in the wings, and Nabel hopes already has compiled on its growing HIV problem eastward into Hebei and Henan. It also spread to be better prepared when they step onstage. v to the international scientific community. northwest from Sichuan, into Gansu and Xinjiang. The meeting began in Beijing and ended Xinjiang, in the far northwest of China, is with a trip to Yunnan Province to visit a vaccine estimated to have between 15,000 and 25,000 Patricia Thomas was editor of the Harvard Health manufacturing facility and a primate facility and people infected with HIV, according to Yuanzhi Letter from 1991to early 1997. Since then, she has to meet Chinese HIV patients. The dogged work Zhang, director of the Center for AIDS Detection been at work on a book about the search for an AIDS of Yiming Shao, deputy director of NCAIDS, and Supervision, Station of Hygiene and vaccine, which will be published in 2001 by Public and his colleagues yielded significant international Epidemic Prevention of Xinjiang Uygur Affairs. Thomas was among the earliest healthy vol- support. The foreign sponsors included the Joint Autonomous Region. Ninety-seven percent of unteers to be injected with an experimental DNA United Nations Programme on HIV/AIDS, the Xinjiang’s 2,341 diagnosed cases of HIV vaccine for AIDS, in a National Institutes of Health US National Institutes of Health (NIH), the infection are IV drug users. Shao trial conducted during 1997 and 1998. European Union, the International AIDS Vaccine explained that almost all known subtypes of the Initiative, the Henry M. Jackson Foundation, and HIV-1 virus have been found in China, although NIH funds via Harvard University and the the majority of cases are B’ and C. A unique C/ University of North Carolina-Chapel Hill. B’ recombinant strain has been traced through Chinese epidemiologists estimate that its transmission via the drug trafficking routes from there are 400,000 people infected with HIV in southern China north to Xinjiang, where it is the the country. By the end of September 1999, only strain of HIV found. HIV has been identified 15,088 cases of HIV infection were identified. in samples from all of China’s provinces and As of that date, a total of 240 deaths in China autonomous regions. Recently, several cases of were attributable to AIDS. HIV-2 were identified in Shanghai, Shao noted. HIV was first identified in China in the The question the Chinese now confront mid-1980s in hemophilia patients who received —and which they posed to the meeting contaminated factor VIII (a blood-clotting factor attendees—is how China can best interface and that is given to hemophiliacs), in several cooperate with researchers worldwide to stop foreigners, and in a few (people of Chinese the spread of HIV before the country faces an ancestry who live abroad, according to a paper Continued on page 5

M olecular Ep idem iology of H IV -1 In fection in C h in a

Ha Erbin

Urumqi Shen Yang

C/ B ' B' Chang Chun

Huhehaote B' A B C B Beijing B' Tian Jing B' Shi Jiazhuang Yin Chuan Tai Yuan Xi N ing C Lan Zhou B' JiNan C/ B' B' Zheng Zhou

Xi an B' B' A C B' Nan Jing Cheng Du Shang Hai A B' Wu Han He Fei Lasa B ' E C C / B' B' HangZhou B' Nan Chang Chang Sha Gui Yang B' E C India C C/ B' Kun Ming Fu Zhou Tai Be i

B' C B' Myanmar E B' B Guang Zhou B E Nan Ning Viet Nam E

B' E Laos E B' B' Thailand Hai Kou Y. Shao, et al E NARL/NCAIDS/CHINA Unpublished data SOURCE: Professor Yiming Shao, National Center for AIDS Prevention and Control (NCAIDS)Beijing,PRC 6SABIN VACCINE REPORT February 2000 Testimonials Bring Deeper Meaning To the Burden of Hookworm

The Albert B. Sabin Vaccine Institute and the Medical Helminthology Laboratory at Yale University under Dr. Peter Hotez have worked and collaborated extensively with China since 1994, and more recently with India. Reprinted below are two examples of how urgent the hookworm problem is and how desperate medical personnel from these countries feel in regards to the disease. The following letters were instrumental in securing funding to make a vaccine against hookworm possible. A Letter From India: Hookworm Weakens an Already Impoverished Nation

heproblemof hookworm disease in each one sucks 0.1 to 0.2 ml of blood per major public health problem. Drugs are Third World countries has been the day. The vast majority are the same available but are cost prohibitive. The Tsubject of investigation for several individuals who suffer from malnutrition, people who are infected are extremely decades. It perhaps outranks all other lethargy and poverty. The highest incidence poor and cannot afford the cost of worm infections of human misery, debility of infection is in wet areas and in coalmines. medicinesin view of repeated and morbidity. In India more than 130 The epidemiological study in India reveals reinfections in endemic areas. So there million people are infected with that the 15 to 20 year age group is is a pressing need for vaccines that can hookworms due to either Ancylostoma commonly infected and a larger segment of prevent hookworms from penetrating duodenale or this population have enough worms to cause and establishing in the gut, a normal site “Though the Necator clinical symptoms of anemia, loss of vitality for the parasite. disease is never americanus or and chronic illness. It is unfortunate that the problem of spectacular like both. The former Though the disease is never spectacular hookworm infection has been ignored by some other parasite, a more like some other diseases but is essentially public health officials in this country as diseases but is virulent pathogen, insidious year after year, generation after the disease does not cause instant death. essentially is distributed generation and undermines the health and [Nevertheless,] the hookworm disease insidious year exclusively in the efficiency of whole communities. Since undoubtedly is one of the major after year, north while the there are hardly any sanitary indoor toilets impediments in the socio-economic generation after latter is prevalent in homes, people have the habit of releasing progress in India and warrants immediate generation and in the rest of the themselves in open fields where hookworm attention for containment of the parasite. undermines the country. eggs are discharged with faeces. With warmest regards, health and Both parasites In course of time they pick up efficiency of whole are voracious infection and reinfection from their own DR. H.G. SEN communities. “ blood suckers as contaminated environment which is a Senior Scientist Hindusthan CIBA-GEIGY A Letter From China: Experts Hope For a Vaccine To Combat Emerging Drug Resistance

ookworm infection is a major major health threat. Working withPeter’s we are working with Dr. Hotez’s group public health problem in the rural group we published papers this year in to develop an alternative strategy through Hareas of our country. Based on Acta Tropica (in press, 1999) which anti-hookworm vaccination. This is a new a nationwide survey between 1988 and show that the prevalence and intensity of idea, but one which we are excited about. 1992 organized by hookworm is the same or even higher than A successful vaccine could prevent the A successful our Ministry of it was 10 years ago! There are several problem of rapid reinfection which occurs vaccine could Health, we had reasons for this, including the continued almost immediately several months after prevent the determined that the use of human feces as fertilizer and anthelminthic chemotherapy, and would problem of rapid overall prevalence inadequate sanitation. This is essentially help us lessen use of anthelminthic drugs. reinfection which of hookworm is the situation in this part of China for Therefore use of an anti-hookworm occurs almost 17%. This number hundreds of years. In the absence of vaccine might also help us prevent immediately is based on aggressive economic reforms in these emerging drug resistance. We could several months 1,477,742 fecal rural areas, it is not reasonable to expect anticipate using a vaccine as part of an after examinations. this situation to change anytime soon. overall anti-helminth control strategy. anthelminthic Therefore we Therefore we anticipate that hookworm Therefore we at the Institute of Parasitic chemotherapy. calculated that rates will decline only in suburban areas Diseases, which is the major parasitic disease there are an close to major cities. component of the Chinese Academy of estimated 194 Unfortunately, albendazole and other Preventive Medicine, hope that you will million cases of hookowrm. Over the last anthleminthic drugs are not adequate for seriously consider the Hookworm Vaccine decade, the prevalence of hookworm controlling hookworm in these rural areas. Initiative proposal submitted by Dr. Hotez. We has decreased in some areas where Unless we administer the drugs several times anticipate that our Institute will continue to aggressive economic reforms have a year, the people remain infected with not collaborate closely with Peter on this project. occurred. The best example of this is in onlyhookworm, but also ascariasis as well. As you may know, there are not many U.S. suburban areas of Jiangsu Province which However, it is usually not possible to administer scientists like Dr. Hotez who have the are close to the large cities, including the drugs to large populations on this frequent commitment to work with institutes such as Shanghai and Wuxi. This study was basis. Therefore the people remain infected. ours to solve problems in developing regions published together with Peter Hotez in the Now we are also worried about anthleminthic of Asia. We greatly enjoy working with Peter. Southeast Asian Journal of Tropical drug resistance, especially to albendazole. Public Health (September 1998). In many ways the problem of Sincerely, However, in the highly rural areas of hookworm is similar to the problems of Feng Zheng, Professor Hainan, Sichuan and even Anhui many helminth infections in China, Institute of Parasitic Diseases Provinces hookworm continues to be a including schistosomiasis. For that reason, Chinese Academy of Preventive Medicine SABIN VACCINE REPORT February 2000 7

Few Lured To Study Hookworm Despite Its Hookworm Glossary Global Prevalence BY CHARLENE A. FLASH relationship with ducks and geese. Helminthology: the study of “As it was when I first saw it, so it is now, one of The complexities of symbiosis would parasitic worms. the most evil of infections. Not with dramatic continue to intrigue Dr. Hotez, as his scientific pathology as are filariasis, or schistosomiasis, pursuits for the next three decades focused on Nematodes: a zoological phylum of but with damage silent and insidious. Now that worms and parasites. At age fourteen, Dr. Hotez worms. These include parasitic and malaria is being pushed back (sic) hookworm volunteered at the Connecticut State Department free-living species. Therefore it is remains the great infection of mankind. In my of Health compiling records of parasite incidence frequently qualified to talk about view it outranks all other worm infections of man in fecal samples. In high school he studied combined... in its production, frequently “parasitic nematodes” or “intestinal earthworms. In college he analyzed the proteins nematodes.” unrealized, of human misery, debility, and of a parasitic worm specific to the African inefficiency in the tropics.” continent. Dr. Hotez received both his medical Ancyclostoma: one of two genera In the 1960’s Professor Norman Stoll of degree and his PhD from R Rockefeller of human hookworms. The other is the Rockefeller Institute eloquently described the University, and it is there that he began studying Necator. disease burden caused by hookworm in an hookworms in particular. address to the New York Society of Tropical Labeled the “germ of laziness,” hookworm Necator: one of two genera of Medicine. Four decades later hookworms infect is indescribably debilitating even though it does human hookworms. The other is more than 1.3 not yield the Ancyclostoma. billion people dramatic Albendazole: a major in Asia, Africa clinical and South manifestation benzimidazole drug used for treating America, of Ebola virus hookworms. haunting the or HIV. The other is mebendazole. world’s When these poorest worms attach Eukaroytes: organisms with a children and

photo compliments of scientific american their teeth-

consigning Ancylostoma Duondenale (l) and Necator Americanus (r) are the most like them to lives prevalent species of hookworm found on the continents of South America, appendages Glossary Hookworm marred by Africa, and Asia. Necator Americanus is also found in Australia. to the walls stunted mental of their and physical development. Hookworm bears intestinal homes in a human host, hemorrhaging China Aids Conference (cont’ from page 5) the dubious distinction of being the second most results. Hookworms cause chronic blood loss prevalent infection of humans; nevertheless, only and thus anemia and protein deficiency; they extremely serious problem. Vice Minister of two laboratories inhibit physical development in children and retard Health Da-kui Yin invited foreign assistance: Labeled the “germ of in the entire world intellectual development. The large-scale social “I welcome everyone to enhance our laziness,” hookworm is are exploring affects hookworm infections have on education communication and collaboration in this indescribably debilitating solutions one and economic progress explain hookworm’s field.” He asked, “Why don’t we cooperate even though it does not being the Medical ability to quietly cause the deterioration of entire together and contribute to this important yield the dramatic clinical Helminthology communities. work?” The important work includes Laboratory manifestation of Ebola Charles Wardell Stiles, one of the early development of vaccines against HIV. directed by Dr. virus or HIV. champions in the battle against hookworm played China already has several ongoing Peter Hotez, a key role in eradicating hookworm from the projects to develop HIV vaccines. Shao chair of the Southern United States. In the international noted that among these are: 1) construction Scientific Advisory Board of the Albert B. Sabin arena, the solutions Stiles discovered and helped of virus-like particles from HIV-1 subtypes Vaccine Institute. His lab is on the front lines of implement will not work because they require B’, C, C/B’, and E that have been placed in battle as the search for an anti-hookworm vaccine changes in agricultural, religious and social a baculovirus system and were expressed in draws ever closer to success. practices in insect cells (in cooperation with University It China, of Regensburg, Germany); 2) using yeast takes a India, and systems to express HIV proteins; 3) unique sub- development of a DNA vaccine (gp120 and individual to Saharan gag p55 clones in a DNA vector) (also in spearhead Africa that cooperation with University of Regensburg); these types have been 4) development of a vaccinia virus vector of efforts, ingrained (Tiantan strain); 5) development of a fowl and one is forpox vaccine expressing subtype B’, C, C/ found in Dr. decades. B’, and E; and 6) development of an Peter Hookworm’s adenovirus expressing B’, C, C/B’, and E. Hotez. As affects can China also has facilities for testing Dr. Peter be best vaccines in primates and for vaccine Hotez nullified by production. The country’s main problems graciously implementation are financial resources. The Chinese accepted photo compliments of the medical helminthology laboratory of an anti- researchers and administrators hope that the 1999 Dr. Peter Hotez’s Medical Helminthology Laboratory has committed with this meeting, foreign researchers will see themselves to developing an antihookworm vaccine. hookworm Henry vaccine in the opportunities for joint research, clinical Baldwin tandem with improved sanitation, use of trials, and epidemiological monitoring in a Ward Medal from the American Society of antihelminthic drugs, and new fertilization country that has good science and Parasitologists, he shared his earliest scientific techniques. technology, a good public health and pursuits when as a child he would look at the epidemiology infrastructure, large murky waters of a nearby pond under his Charlene Flash is a research fellow at the Albert populations for clinical trials, and a microscope and marvel at the wonders he saw. B. Sabin Vaccine Institute and Editor-in-Chief of commitment to HIV vaccine development. In that watery microscopic world he encountered the Sabin Vaccine Report. daphnia and learned of their symbiotic 8SABIN VACCINE REPORT February 2000

WHO, UNICEF, CDC, Rotary Intensify Polio Eradication Efforts

BY NISHIENA GHANDI during National Immunization Days (NIDs), warring parties, and we need to improve c) acute flaccid paralysis surveillance whereby surveillance systems so that every paralyzed lobal polio eradication as defined by every single case of child paralysis must be investigated, child is investigated for polio and we can World Health Organization (WHO) and confidently say that countries, regions, and Ginvolves the complete interruption of d) “Mopping up” immunization activities which eventually the entire world are polio-free.” wild polio transmission. Efforts to achieve are in place to re-immunize children in high-risk areas. To address the changing needs of the eradication by the year 2000 have been The last case of polio in the Western hemisphere initiative in the last and final phase of eradication, underway since the late 1980s. In fact, the Polio occurred in Peru in 1991 and in the Western pacific a new set of priorities were identified during the Eradication Initiative region in Cambodia in 1997. 1999 meeting of the Social Mobilization Advisory was launched in May There were only 6000 cases of Group for Polio eradication which included 1988 at the World polio reported world-wide in UNICEF, WHO, Rotary International, Basics, Health Assembly’s 1998 which represents a decrease Change, Voice of America, CDC, USAID, World annual meeting in of 85 percent of cases as Bank, ARCH (Harvard University) and PCS Geneva. At that time compared to the 350,000 cases (Johns Hopkins University). this governing body of reported in 1988. Although The need to WHO resolved to significant progress has been improve the quality of Although significant eradicate polio from made to date, there are still three National Immunization progress has been the world by the year major reservoirs where polio Days was discussed made to date, there 2000. The success of transmission occurs: South Asia, and it was determined are still three major this initiative, however, West Africa, and Central Africa. that in order to obtain reservoirs where depends on Forty-eight countries are presently a better understanding polio transmission collaboration of many known or suspected to be of the immunization occurs: South Asia, public and private endemic, and recent polio status of a region and West Africa, and partners, including the outbreaks such as those in Angola deliver vaccines Central Africa. United Nation’s Photo by Charlene Flash and Eastern Europe call for an comprehensively, dis- Children’s Fund Mia Farrow, actress and mother of a son with intensification of eradication aggregated data on (UNICEF), which polio, speaks at the Progress of Nations at the activities. The Polio Eradication coverage needed to be generated so that provides the oral polio UN in 1999. Initiative has in particular identified populations with inadequate coverage can be vaccine; the U.S. Centers India, Bangladesh, Pakistan, identified. This would improve the accuracy for Disease Control and Prevention, which offers Sudan, Somalia, Democratic Republic of Congo of the target population and enable technical expertise; and the service organization Rotary (DRC), Ethiopia, Angola, Afghanistan and Nigeria as immunization efforts to be more focused. , International, whose 1.2 million members in 159 priority countries. Additional efforts focus on giving children in countries have made polio eradication the main focus In its final and most crucial phase, the major regions of conflict access to immunization, of their fund-raising and volunteering. challenges in the initiative have been identified as increasing support for the ten priority countries, The polio eradication initiative is currently in its stopping polio transmission in endemic countries and improving surveillance methods. final and most crucial phase. Although some observers especially those in conflict, and strengthening The number of worldwide cases of polio have suggested that the campaign may take until 2003 surveillance and laboratory networks. To achieve has dropped by almost 90% since the to eliminate paralytic polio,the World Health Assembly the termination of transmission, WHO urges its campaign began 10 years ago. The great delegates and two independent expert advisory groups member nations to improve vaccine coverage majority of countries are already polio-free, to WHO, The Global Technical Consultative Group beyond the already impressive rate of nearly 90 and the 6,415 confirmed cases in 1999 came for Polio Eradication and the Scientific Advisory Group percent. They are advocating, “Immunizing every mostly from the Indian subcontinent and sub- of Experts at their 52nd annual meeting in May 1999 in child because every child counts.” Saharan Africa. From now on, WHO hopes Geneva, Switzerland, asserted that “established Rotary International, a nonprofit to investigate each singular case to better eradication strategies, when fully implemented, will organization which has played a leading role understand the specifics around the infection. achieve eradication by the target date.” Accelerating in polio control, addressed Gro Harlem Specific populations have been targeted and efforts in reservoirs such as Angola and Bangladesh Brundtland, the WHO’s Director-General, to surveillance efforts have increased. With make eradication by the end of the year 2000 is still a offer its 1.4 million volunteers as “foot soldiers” continuing effort on the part of WHO and other reasonable goal. in the eradication effort. Dr. Brundtland health and volunteer agencies, a polio free world The strategy developed by WHO and its warned, “One of the paradoxes of an seems possible within the next three years if not partners to eradicate polio is four-pronged: eradication initiative is that control efforts must the next 11 months.v a) a strong routine immunization program via the be intensified as the disease disappears. We effective and inexpensive oral polio vaccine, need to accelerate house-to-house delivery of Nishiena Ghandi is a Master’s Candidate at the b) supplementary additional doses of OPV the vaccine ... and continue negotiations with Yale University School of Public Health.

Remembering Polio: Karen Veronica Recalls the Polio Scourge BY CHARLENE FLASH In these first months of the new year, cube containing the Sabin oral polio vaccine Foremost however was the fear of Polio. In those of us trying to clean up and clean out dose. After the days when the townspeople those days, “People were always thinking encounter memorabilia of days long gone. lined up for their sugar about it,” Karen Veronica, Executive Director and cubes, she recalls they according to Ms. Founder of an HIV/AIDS hospice in breathed a “collective Veronica. During Connecticut called Bread & Roses, chanced sigh of relief.” the hot summers upon a single wrinkled sheet documenting the During that post- parents, rich and day she received her polio vaccination. Ms. World War II era, a poor alike, Veronica remembers the seemingly never- general sense of fear restrained their ending line outside the newly constructed cloaked adults and children from Junior High School in her home town of children alike with the swimming for fear Berea, Ohio population 20,000, where her beginnings of the Cold they might siblings, parents, and neighbors patiently War and the shroud of contract this

awaited their turn to take the contents of a infectious diseases like Photo by Charlene Flash dreaded viral The iron lung was used in the first half of the century little white cup holding the precious white influenza and polio. to enable paralyzed polio vistimes to breathe. illness by ingesting SABIN VACCINE REPORT February 2000 9

International Leaders Seek Solutions to Developing World Challenges Cold Spring Harbor Colloquium Tackles the Issue of Affordable Vaccines

BY PETER HOTEZ this disease predominantly afflicts not only the issues of R&D, payment structure and poorest countries in places regions as sub- macroeconomics. Yet for the most part, our political hile most of us think of December Saharan Africa, but in particular the poorest of and spiritual leaders, our legal and medical scholars, 7 as a day that will the poor in these developing nations. What then our ethicists and artists, have remained silent about W“live in infamy” because of its is the incentive for major vaccine producers to our ability to combat the great plagues of AIDS, TB, association with the bombing of Pearl Harbor, in invest the hundreds of millions of dollars in R&D, malaria, dengue, hookworm. In this sense there is a 1999 that date also witnessed a remarkable day manufacture and post-license marketing that conspiracy of silence. Our colloquium attempted to of human compassion. Between December 5 and would be required to produce an anti-malaria break the conspiracy of silence about development 7 last year, the Sabin Vaccine Institute held a vaccine? Case studies presented for not only of vaccines for the great neglected diseases of colloquium at Cold Spring Harbor humankind, such as AIDS, TB, Laboratory, which brought together malaria, dengue, hookworm. This leading economists, international health meeting broke the silence. policy experts, philanthropists, vaccine The colloquium reaffirmed manufacturers, and physician-scientists that combating infectious diseases in order to tackle one of our greatest must be accorded a central role in social challenges - namely how will we international strategies for improved afford the next generation of vaccines public health, poverty reduction, for developing countries. Over these and economic development in the two days an extraordinary team of heavily indebted poorest countries experts selected from such diverse (HIPCs). A number of novel push organizations as the White House Office and pull funding strategies were of Science and Technology, the U.S. outlined to provide mechanisms by Treasury Department, the National which to solve these issues. These Security Council, World Bank, were put forward with some urgency Photo by Charlene Flash UNICEF, Global Alliance for Vaccines because of a series of key actions and Immunization (GAVI), WHO, Dr. Peter Hotez (left) of Yale University and Dr. Jeff Sachs (right), Director of anticipated in the YR 2000. These the Center for International Development at Harvard University, co-chaired International the colloquium at Cold Spring Harbor. include finalization and submission to Our technical AIDS Congress of the FY 2001 abilities to employ Vaccine Initiative (IAVI), malaria, but also HIV, dengue fever and Administration budget; parliamentary budget cycles modern GAVI, WHO, IAVI, the hookworm infection illustrated over and over in Europe, Japan, and Canada; a White House biotechnology for the Bill and Melinda Gates again that “business as usual” would never result meeting early next year, following up on President manufacture of these Foundation, economic in the Clinton’s U.N. address this Fall; ongoing desperately needed think tanks, leading The colloquium reaffirmed that successful preparation for the G-7 Summit in Japan in June vaccines have universities, and major combating infectious diseases development 2000; a planned Summit of African Leaders on outpaced our vision. private sector must be accorded a central role of vaccine Malaria next Spring to be hosted by Nigeria and representatives from in international strategies for to fight supported by the WHO; the launch of the enhanced Merck, Wyeth, SmithKline Beecham, and Glaxo improved public health, poverty these HIPC initiative on debt relief; decisions by the Wellcome debated and explored innovative reduction, and economic devastating Executive Board of the World Bank. solutions for a pressing issue that will affect hundreds development ... illnesses. The Colloquium has launched a concerted of millions of children in less developed countries. Thus, effort by the pharmaceutical industry, GAVI, and The problem we focused on was how we although it other participants to work intensively over the next can encourage the development of desperately is now possible to apply modern techniques year. Extraordinary interdisciplinary leadership of needed vaccines for which the markets either do developed by academia and the biotechnology vision and wisdom is needed to seize this unique not exist or are grossly inadequate. For instance, industry to make vaccines for these ancient and opportunity and find solutions. Our goals will be falciparum malaria kills an estimated 1-2 million emerging scourges, we now find ourselves in an to ensure that an expanded global vaccine effort children under the age of 5 every year. This disease unusual and distressing situation. Our technical is brought to fruition.v is arguably the single leading killer of young abilities to employ modern biotechnology for the children in the world. The biotechnology is now manufacture of these desperately needed Peter J. Hotez is the director of the Medical Hel- available to begin making a serious attempt to vaccines have outpaced our vision. Our minthology Laboratory at Yale University and is develop a safe and effective malaria vaccine. Yet, technology is exceeding our wisdom. This is also an Associate Professor at the School of Public occurring at several different levels, regarding the Health and Epidemiology .

water contaminated by infected feces. for his parents and siblings filled each house. of negative health encounters such as being Ms. Veronica chuckles as she Although he left school, the constant hum of treated as a second-class citizen when going in remembers preparing for her family vacation conversation about his ailment made his presence for STD testing. This experience was proactive, to northern Michigan by picking out an extra felt. “That’s all we talked about. We all sent clean, upbeat, all-inclusive and it made sense. bathing suit— an extravagance at other times cards.” Paralysis of individual muscles is one of Most importantly it erased the fear. — but a necessity because she was not the symptoms of polio, and a few years later he Now as executive director and founder allowed to even sit by the crystal clear lake returned to school with a “bad limp.” Many of her of Bread & Roses, Karen Veronica strives in a wet bathing suit. Though she could not friends did not know how to approach the topic to create positive health experiences for understand how the crystal clear waters of of his limp, the calling card of his bout with polio. people suffering with HIV or AIDS. She the lake could hold anything infectious or It was a tragic curiosity. He and his family later and her staff “walk alongside people with bad, she was excited at the prospect of a moved away from Berea. AIDS, through direct care, education, new bathing suit. The actual vaccination process stands out in outreach and advocacy.” v In about the fifth grade one of Ms. Ms. Veronica’s memory as one of her best public Veronica’s classmates contracted polio. health experiences. She recalls her polio News spread through her community as pity vaccination as a positive experience among a host 10 SABIN VACCINE REPORT February 2000 Lessons learned; opportunities missed The Politics of International ravage children of the Third World. once CVI was officially based inside WHO. In When formed in 1990, the CVI was intended addition, Muraskin predicts what can best be Health: to act as a facilitator in the product development described as the slow death of the CVI once it was Children’s aspect of vaccine research, especially on the subordinated by WHO. He writes: Vaccine international level. Immunization efforts in the Third “…CVI leaders believed WHO was Initiative and World were severely hampered by a communication incapable of doing what the CVI did: [being] the Struggle to gap between the public and private sectors, and the flexible…seizing opportunities, attractive to outside founders of the organization that would evolve as agencies, working comfortably with the private Develop the CVI hoped to bring together researchers, sector, seeking out the best people. The tendency Vaccines for developers, and health networks. Muraskin of WHO to subordinate expertise to equal the Third described the process of vaccine development as representation of nations and regions…differentiated World “a disarticulation.” As he clearly explains in writing it from the CVI. The WHO’s corporate culture was William to both the scientific and the lay community: simply the wrong place for the CVI. In addition, Muraskin, State …shelves of research facilities were filled with groups [like] UNICEF would not financially support vaccines...not picked up as a usable commodity. programs implemented by WHO.” University of New York Press, 1998 [Health agencies] delivering vaccines…had little Indeed CVI Coordinator Roy Widdus wrote BY VERONICA KORN interaction with scientists or commercial interests. in the final issue of the CVI Forum, the organization’s They are forced to work with whatever vaccines newsletter (no.18, July 1999), that because WHO Published shortly before the controversial the other two groups [researchers and private sector was a public-sector agency, it could not “formally dissolution of the Children’s Vaccine Initiative (CVI) developers] have decided to work on.” integrate” private partners into a true coalition, as in March 1999, William Muraskin’s The Politics Although the coordination of a three-fold had been the initial vision of the CVI. of International Health: The Children’s Vaccine system that would involve researchers, developers, It seems almost inevitable that the CVI itself Initiative and the Struggle to Develop Vaccines and those ultimately responsible for delivering would eventually become something of the past. for the Third World is an in-depth exploration of vaccines in the field was one of the CVI’s initial Muraskin’s work describes a relatively simple that organization’s vision and effort to bring together undertakings, the real impetus lay in involving the solution to some international health problems: a the private and public sectors to target vaccine public sector more in vaccine product development. diverse coalition cooperating to find and deliver development for the nations of the Third World. Muraskin takes the reader on a journey through vaccines to the Third World, where immunization Muraskin’s predictions that the future of the CVI the private sector, beginning with the attitude of rates are extremely low and disease rates are seemed precarious were accurate, as it turns out. complacency towards vaccines, despite their enormous. Yet, each chapter is filled with power Through many short and lively interviews and potential to change the face of the Third World, and struggles and competition among key international quotes, the author highlights the difficulties in this then describing the dawning realization that new players with good intentions but without the ability process and the differences in the organizational biotechnology would make vaccines very profitable. to play together as a team. Muraskin concludes his cultures of the key players. All the while, the author intertwines the role of the book by focusing on the far-reaching successes of Created at the World Summit for Children in public sector in this process as it endeavored to put the CVI: its legacy of stirring interest in vaccine 1990, the CVI was born out of inspiration and aside its suspicion of the private sector’s commercial development and production across the international humanitarian vision on the cusp of a revolution in interests and the subsequent formation of the CVI health scene; the renewed interest of organizations biotechnology that would make vaccine production for a fascinating historical account. like WHO in taking on effective roles in health; the more affordable and carve out a place for vaccines Despite the unfortunate timing of the CVI’s establishment of the International Vaccine Institute as a profit-making entity. Co-sponsored by the origins from an economic standpoint, as the world in Seoul, Korea, which is wholly dedicated to United Nations Children’s Fund (UNICEF), the UN economy entered a recession in 1990, Muraskin vaccine research and development; and a Development Programme (UNDP), the World points out that its failures and frustrations were really revolutionary plan to coordinate the work of Health Organization (WHO), the World Bank, and more the result of decision-making and in-fighting private and public sectors involved in vaccine the Rockefeller Foundation, the CVI was a unique among the players in such health network giants as production from beginning (development) to end global coalition of public, non-governmental, and the WHO and UNICEF. He describes the dissimilar (delivery). The lessons learned from the private organizations. Its original goal was to corporate cultures, personality clashes, and cultural endeavors of the CVI are thought provoking, develop a single oral vaccine that could be given to differences that oftentimes fueled a heated especially when one considers the challenges of newborns shortly after birth to prevent more than competition between the two agencies. Most vividly, immunizing almost 4 million children who, twelve deadly diseases. Vaccines are the least he describes the absorption of the CVI into WHO, without vaccines, will die annually from vaccine- expensive and most effective means of disease the ensuing struggle between the agencies, and preventable diseases. prevention against many infectious diseases that still WHO’s inability to reach the important private sector Find out more about the Children’s Vaccine Ini- tiative at http://www.vaccines.ch. Merck CEO and Honduran First Lady to Receive Sabin Awards Celebrating Health in the Americas BY JOHN M. CLYMER and rotavirus, a major cause of acute diarrhea and cation of polio throughout the Americas, and the he Albert B. Sabin Vaccine Instit1ute has dehydration in infants. ongoing campaign to eradicate measles from the selected Raymond V. Gilmartin to receive Mr. Gilmartin’s Western Hemisphere. Tthe 2000 Sabin Lifetime Achievement emphasis on re- Merck is an established leader in solving Award and Mary Flake de Flores to receive the cruiting and re- health problems in developing countries. After Albert Sabin Humanitarian Award. The awards taining a talented Merck discovered that one annual dose of its will be presented at a black tie dinner on Wednes- workforce has Mectizan® (ivermectin) drug prevents river blind- day, May 31 at The Pierre Hotel in New York City. helped Merck be ness, it decided in 1987 to donate Mectizan® free Mr. Gilmartin is chairman, president and named the best of charge to all people affected by river blindness. chief executive officer of Merck & Co., one of pharmaceutical It formed a partnership of industry, nongovernment the principal vaccine research and development firms to work for development organizations, and nongovernment or- companies in the world.Mr. Gilmartin has invested in the U.S. by ganizations to help it distribute the drug in African heavily in vaccine research. During his tenure, Merck Fortune maga- and Latin American countries where river blind- Compliments of Merck &Co. has introduced the only vaccine that prevents Ray Gilmartin, Chairman, zine. ness is prevalent. The company donates approxi- chickenpox, as well as vaccines against hepatitis A President and CEO of Merck The theme for the mately six million doses of Mectizan® annually. And, and Haemophilius influenzae type B (meningitis). & Company dinner is “Cel- it has created a donation and distribution model that The company’s pipeline features vaccines to prevent ebrating Health in can be used to address other disease threats. HIV/AIDS, human papillomavirus/cervical cancer, the Americas.” It will focus attention on the eradi- The first lady of Honduras, Mrs. Flores, SABIN VACCINE REPORT February 2000 1 1 Cancer efforts at Critical Stage Show Promise Report from Walker’s Cay Cancer Vaccine Colloquium

BY ALLAN GOLDSTEIN underscored by Dr. Carl June, Director of has several cancer vaccines in its R&D pipeline, translational research programs at the Leonard most of which have produced encouraging hirty of the leading U.S. cancer and Madlyn Abramson Family Cancer Research results in clinical testing. “No one can do it researchers presented work at the 2nd Institute at the University of Pennsylvania alone,” Panicali said. “Every one of the T Annual Walker’s Cay Colloquium on Cancer Center. June, a participant in the 1999 promising products in our pipeline is the result Cancer Vaccines that indicates we are on the and 2000 meetings, reviewed a case in which of this consortium that allows the NIH, verge of a major victory in the “war on cancer.” he developed a new biochemotherapy for a academic research centers and our company “We are seeing meaningful results in the patient with a recurrence of ovarian cancer in to stick to our strengths and combine our best development of weapons to treat and prevent April 1999. He incorporated experimental efforts to develop effective cancer various types of cancer,” said Allan Goldstein, materiel developed and disclosed by other immunotherapies.” Chairman of Biochemistry participants in The Walker’s Cay Colloquium is a think and Molecular Biology at the 1999 tank-style meeting. Ralph A. Reisfeld, George Washington meeting. professor of immunology at the Scripps University School of June’s therapy Research Institute and co-chair of the Medicine and a participant appears colloquium, said the meeting is “distinctive for in the meeting. “Recent successful at its small size and its emphasis on lively, open advances in immunology this juncture; discussion.” The colloquium atmosphere are now being applied the cancer is in encourages free exchange of data and develop novel to vaccines remission and information about the latest advances being for cancers and the results the patient is made in cancer vaccine design and are encouraging,” he said. physically immunotherapy. Participants share unpublished The goal of the Photo by Charlene Flash active. data and conclusions in discussions that spark meeting convened by the Participants enjoy the surroundings at the Walker’s Cay “Without this new ideas and experiments. Albert B. Sabin Vaccine sharing of The site of the meeting, Walker’s Cay, is Institute was to shorten the time needed to unpublished data and information at last year’s a small island in the northern Bahamas owned translate scientific discoveries to meaningful meeting, I would not have known about these by Robert Abplanalp, chairman and chief treatments for cancer. The work presented brand new therapies, so I could not have executive officer of Precision Valve there “indicates that we are at the stage of fine incorporated them into this cocktail. I Corporation. Richard Nixon was a frequent tuning therapeutic and prophylactic cancer contacted these investigators and they were visitor to Walker’s Cay during his presidency. vaccines,” Goldstein observed. extremely helpful in sharing additional data and The secluded tropical island provided solitude A number of novel cancer vaccines using providing materiel to me,” June said. His clinical as he pondered major decisions. He was at combinations of the patients own cancer and dentritic protocol therapy Walker’s Cay when he decided to commit the cells plus cytokines have now entered human trials, has just been A number of novel cancer United States to a “war on cancer.” have shown remarkable regression of advanced approved for a vaccines using The “war” began with enactment of the tumors and restoration of anti-tumor immunity. Phase I trial in combinations of the Cancer Control Act of 1971 which greatly These results provide proof of principle for a vaccine patients with patients own cancer and increased National Institutes of Health funding approach to cancer treatment. advanced ovarian dentritic cells plus for cancer research. Elliot Richardson, secretary “Scientists in multiple disciplines have made cancer. cytokines have now of Health, Education and Welfare at the time, extraordinary advances in molecular biology and Formation entered human “directed [funds] into areas of basic research genetics over the past few years,” Goldstein of a vaccine trials...these results that offered significant promise of shedding light observed. “These advances have vastly increased biomedical provide proof of principle on the fundamental causes of cancer” such in our understanding of the role of cellular components consortium, for a vaccine approach to molecular biology, he wrote in a 1999 letter to of the immune system and the soluble growth factors which the Sabin cancer treatment. Sabin Institute chairman H. R. Shepherd. and cytokines produced by T-cells, NK cells, Vaccine Institute Twenty-nine years later, that research is paying macrophages and dendritic cells responsible for has advocated for several years, was discussed off with experimental vaccines to prevent and antitumor activity. This knowledge has resulted in at the 1999 colloquium. This year, Dennis treat a variety of cancers. the development of novel cancer vaccines which Panicali, chief executive officer of Therion Allan Goldstein is a Professor and Chairman of are now being tested humans,” he added. Biologics, reported on an industry-government- the Department of Biochemistry and Molecular That approach to treating cancer and the academia consortium formed by his company. Biology at the George WashingtonUniversity in colloquium’s impact on scientific progress were Therion, a closely-held biotechnology company, Washington, D.C.

will be recognized for leading both public and pri- an effort led by Mrs. Flores.Currently, Mrs. Flores its of her book, Virgencita de Suyapa, to vate efforts to prevent disease and improve is raising private funds to build a children’s hospital the foundation. healthcare in Honduras. Her involvement in this in the country’s capital, Tegucigalpa. She is founder “Mary Flake de Flores is a tireless advo- arena began in the 1970s, long before her husband’s cate for better healthcare for Hondurans and all January 1998 election as president. She is an out- peoples of Central America,” said Sabin Vaccine spoken advocate for immunization. Her leader- Institute chairman H. R. “Shep” Shepherd. “Like ship helped the XIX Vaccination Crusade in May Albert Sabin, she is dedicated to preventing dis- 1999 reach 95% coverage nationwide. She ob- ease. She rolls up her sleeves and does the heavy tained a donation from Merck of one-third million lifting that is required to truly make a difference.” doses of measles, mumps and rubella vaccine, Mr. Shepherd praised Mr. Gilmartin as “an which were used in the crusade. extraordinary corporate leader who is focused on Mrs. Flores formed Fundación María, a more than meeting Wall Street’s expectations for nonprofit organization dedicated to ameliorating the next quarter. He has strengthened Merck’s com- poverty, and improving health conditions, educa- Mary Flakes de Flores, First Lady of Productions Compliments of Vogue mitment to preventive health care, investing in re- tion , recreation and sustainable development for Honduras search, bringing innovative vaccines to market, and Hondurans. In the aftermath of Hurricane Mitch creatively applying Merck’s resources to prevent in October 1998, the foundation distributed hu- and honorary president of the Honduran Founda- disease in all corners of the world, rich and poor manitarian aid to people left homeless by the storm, tion for Children with Cancer. She donates the prof- alike. Although Ray is young,Continued he already on page has 12 established a legacy as an astute executive and a global citizen,” Shepherd said. Victor J. Menezes, chairman and chief 12 SABIN VACCINE REPORT February 2000 NEWS FROM THE INSTITUTE CYRO DE QUADROS RECEIVES SABIN GOLD MEDAL

Dr. Ciro de and immunization can transcend political Quadros, boundaries and tensions. Dr. de Quadros director of the continues to blaze trails in vaccine diplomacy, Pan American working to make all peoples healthier and to sabin calendar Health break down barriers to peace.” The Institute is not responsible for Organization’s Dr. de Quadros earned his medical degree non-Institute events listed below. Division of in 1966, and a master’s in public health in 1968. April 30, 2000 Vaccines and He joined PAHO in 1977 after working on Albert B. Sabin Gold Medal Awards Immunization, smallpox eradication in Ethiopia. He led polio Renaissance Hotel, Washington, DC will receive the eradication efforts in the Americas, from 1985 DR. CIRO DE QUADROS, Albert Sabin to 1991 when Peru reported the last case of DIRECTOR OF THE PAN AMERICAN Compliments of PAHO Gold Medal polio. Efforts continue to globally eradicate polio HEALTH ORGANIZATION’S Ciro de Quadros, for his roles in by 2003. PAHO, which also serves as the DIVISION OF VACCINES AND Director of the Pan the eradication Regional Office for the Americas of the World IMMUNIZATION, WILL RECEIVE THE of polio and Health Organization, works to improve health ALBERT SABIN GOLD MEDAL FOR measles from the Western Hemisphere. and living standards in the Americas. HIS ROLES IN THE ERADICATION OF “Ciro de Quadros is an extraordinarily apt Dr. D.A. Henderson, a 1999 Sabin Gold POLIO AND MEASLES FROM THE choice for the Sabin Gold Medal because he upholds Medal recipient who led the successful global WESTERN HEMISPHERE. Albert Sabin’s ideals and quest to conquer disease smallpox eradication program, will present the with vaccines,” says H.R. Shepherd, chairman of the award to Dr. de Quadros at the 3rd Annual October 5-7, 2000 Cold Spring Harbor, NY Sabin Vaccine Institute. “Dr. Sabin showed us that, Conference on Vaccine Research in Washington, INTELLECTUAL PROPERTY IN A just as viruses know no borders, vaccine research D.C. on April 30. v PHILANTHROPIC WORLD Sponsored by the Sabin Vaccine Institute and organized by Jeffrey Sabin Institute Establishes Satellite Office in Sachs, M.D. Ph.D. and Peter Research Corridor Hotez, M.D. Ph.D. “A consistent mission pursued through dynamic Fran G. Sonkin recently joined the Sabin May 31, 2000 programs,” is chairman H. R. Shepherd’s assessment Institute at its New Canaan headquarters as Executive Dinner to Honor Ray Gilmartin of the Albert Sabin Vaccine Institute. The Institute Vice-President. Reporting directly to the Chairman Pierre Hotel, NY, NY was founded in 1993 to carry on Albert Sabin’s H.R. Shepherd, Sonkin will direct all major operations RAY GILMARTIN, CEO OF MERCK commitment to disease prevention through of the Institute. She received her Masters in PHARMACEUTICALS WILL RECEIVE immunization. That is our guiding principal even as International Relations at Columbia University. THE LIFETIME ACHIEMVEMNT the Institute evolves,” he explained. You may contact the Sabin Vaccine Institute at AWARD FOR HIS OUTSTANDING Based in New Canaan, Connecticut since its the following locations and numbers: CONTRIBUTIONS TO VACCINE founding, the Institute recently moved its Washington DEVELOPMENT. satellite office from the Georgetown University Office of the Chairman campus to Rockville, Maryland. The New Canaan 58 Pine Street July 5-8, 2000 executive office coordinates all research New Canaan, CT 06840 Washington, DC Marriot Wardman Park Hotel advancement, educational, and advocacy programs, Tel. 203-972-7907 34TH NATIONAL IMMUNIZATION and communications including the Sabin Vaccine Fax 203-966-4763 CONFERENCE Report and the Institute’s World Wide Web presence. The satellite office headed by Dr. Philip K. Russell, Washington Office September 7-10, 2000 the Institute’s founding president, supports the 6290 Montrose Road New Orleans, LA Institute’s research advancement initiatives. The Rockville, MD 20852-4163 38TH ANNUAL MEETING OF THE satellite office is located closer to the National Tel. 301-231-7092 INFECTIOUS DISEASE SOCIETY OF Institutes of Health and the Food and Drug Fax 301-231 AMERICA Administration in Maryland’s biotechnology corridor. www..sabin.org

Gilmartin, Flores (cont’ from page 10) Vaccines for Developing Economies, Who will pay? précis 5 December – 7 December 1999 Cold Spring Harbor Laboratories Cold Spring Harbor, NY 11724-2213 Compiled by Charlene A. Flash

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v For your copy please call: Annual Vaccine Colloquium Annual Vaccine The Sabin Vaccine Institute The Sabin Vaccine th 203.972-7907 or fax 203.966-4763 5 email:[email protected]