MAY 2010 | VOLUME 8 | NUMBER 3

vThe Bulletina on AIDS Vaccinex Research [SPOTLIGHT] AIDS Vaccine Trials Go Viral Investigators tap social networking to pique interest and boost enrollment in vaccine trials By Regina McEnery

Along with traditional outlets like seem to fit the requirements for enrollment. women who have sex with men. The trial is billboards, newspaper and radio advertise- Trial sites are also using social media to testing the safety and efficacy of a combina- ments, printed handouts, and social events, reach potential volunteers in their regions. tion of two AIDS vaccine candidates that many clinical research centers are now also A trial site in San Francisco recently posted are administered sequentially in a prime- tapping into social media with relish to try a video (available at www.SFisReady.org ) boost regimen. Volunteers first receive to generate interest among potential volun- of nine volunteers who had participated in three vaccinations with a DNA-based can- teers for AIDS vaccine clinical trials. previous vaccine trials talking about what it didate that contains non-infectious HIV Since its launch last summer, approxi- was like to participate and addressing some fragments or immunogens, followed by a mately 250 of the planned 1,350 volunteers of the misconceptions regarding AIDS vac- second vaccine candidate that employs an have been enrolled in HVTN 505, a Phase cine candidates. inactivated strain of the common cold II trial that is being conducted by the HIV Jennifer Sarche, director of community virus, known as adenovirus serotype 5 Vaccine Trials Network (HVTN) at 15 programs for the HIV Research Section of (Ad5), to ferry HIV immunogens into the sites in 12 US cities. With the pace of enroll- the San Francisco Department of Public body to provoke an immune response ment slower than investigators would like, Health, says viewers can easily share the against HIV. Neither vaccine candidate can several of the sites have turned to social video with friends on Facebook or MySpace. cause HIV infection. media and online classifieds to try and Sarche views the use of social media Participation in HVTN 505 is also lim- draw volunteers to the study. strategies as part of a larger goal of com- ited to volunteers who do not have pre- Using the Internet to draw attention to munity education. “We believe the Internet existing immunity to the naturally circu- AIDS vaccine trials is not new, of course. is a place for people to learn more about vac- lating Ad5 virus because the results of the HVTN established a separate website for cines at their own pace,” she says. “Then, if STEP trial, which involved a different the STEP trial, a Phase IIb AIDS vaccine a person has seen that their friend is one of trial that was launched in 2004, and its our sites’ fans, and has watched our videos, companion study, known as Phambili, and read more about it, they’ll be a person ALSO IN THIS ISSUE which was launched in South Africa in who is more likely to stop and talk when 2007. But now, trial sites are also utilizing they see one of our recruiters on the street. GLOBAL NEWS social media, such as Facebook. Half of our enrolled participants have come u Combating Poverty Through Vaccine Although it does not recruit volunteers from that active street outreach.” Development and Distribution for the individual trial sites, HVTN’s head- quarters has been posting information A little help from your friends PRIMER about HVTN 505 on its Facebook page and For HVTN 505, investigators are seek- u Understanding if Broadly Neutralizing posting advertisements on the Facebook ing to enroll HIV-uninfected men who have Antibodies are the Answer pages of individuals whose demographics sex with men (MSM) or transgendered

WWW.IAVIREPORT.ORG | VAX MAY 2010 Ad5-based candidate, suggested that male from doing something altruistic, like join- contacts the individuals to ask if they would volunteers who received the vaccine had a ing a vaccine trial. consider participating in the study. Coco higher risk of acquiring HIV if they were It’s not clear how much of an impact Alinsug, Fenway Institute’s recruitment uncircumcised and had pre-existing anti- the use of social media will ultimately have coordinator, says the site has screened about bodies against the Ad5 vector, as com- on enrollment for HVTN 505. Peggy 90 MSM for the HVTN 505 trial, and pared to placebo recipients with the same Johnston, director of the Vaccine Research enrolled about 17 of them, most of whom characteristics. Program in the National Institute of were found through their online efforts. In fact, the STEP trial results may be Allergy and Infectious Diseases’ Division Some individuals, moved by a desire to part of the reason enrollment in HVTN of AIDS, which developed the two vaccine support AIDS vaccine research, have taken 505 has been slow. Cheryl Stumbo, a com- candidates being tested in the HVTN 505 social media into their own hands by creat- munications specialist at HVTN’s head- trial, says while no “immutable deadline” ing personal blogs that encourage others to quarters in , says that some trial sites has been set, the goal is to complete the volunteer for a . Three months are still confronting a skeptical public that trial within four and a half years after ago, Memphis resident Andrew Prislovsky is unsure whether the vaccine candidate enrollment of the first volunteer. Johnston began blogging on his website, the Acciden- could actually work given that the Ad5 can- says the shelf life of the vaccine is not usu- tal Activist, about his experiences as a vol- didate tested in the STEP trial was not ally a factor in determining trial futility. unteer in a vaccine trial known as HVTN effective. “Unless trial length is predicted to be 080. The Phase I trial, launched in Novem- Stumbo says other factors are also to so long that the total cost becomes fiscally ber 2009, involves 48 volunteers and is blame for the sluggish pace of enrollment in indefensible, or if results from other trials designed to assess the safety of and immune HVTN 505, including the economic reces- become available and make HVTN 505 responses induced by a DNA-based vaccine sion, which she said has “put some people irrelevant, NIAID remains committed to candidate. in bad moods,” and may be delaying them the completion of HVTN 505,” says Prislovsky says his sister’s difficult, but Johnston. ultimately successful, battle with breast cancer moved him to join a trial, but it was Targeted recruitment World AIDS Day that propelled him to get Other efforts at using social media to involved specifically with HIV/AIDS. boost enrollment involve online classifieds After he enrolled in HVTN 080, Pris- vax and blogs. After obtaining approval from lovsky learned from the director of the the trial’s Institutional Review Board, the Nashville trial site about its struggles to MANAGING EDITOR Fenway Institute (formerly Fenway Com- find volunteers for some of its AIDS vac- Kristen Jill Kresge munity Health) in posted a listing on cine studies. That’s when he decided to SENIOR SCIENCE WRITER two separate craigslist pages seeking volun- blog about his experiences. “My whole Andreas von Bubnoff, PhD teers for HVTN 505. In addition, a Fenway point is that the average person can do recruiter combs craigslist’s personal ads something,” says Prislovsky. “I’m just a SCIENCE WRITER looking for people who appear to fit the eli- cog in the wheel, but 30 years from now it Regina McEnery gibility requirements for the trial and then might make a difference. g PRODUCTION & WEBSITE MANAGER Nicole Sender GLOBAL NEWS By Regina McEnery FREE SUBSCRIPTIONS: To obtain a FREE subscription to VAX by e-mail, change Combating Global Poverty Through Vaccine your subscription details, or receive multiple print copies of VAX to distribute and/or use in your programs, please go to Development and Distribution www.iavireport.org and click on the Subscribe link. VAX is a monthly bulletin from IAVI Report, the publication In some ways, vaccine development US$10 billion over 10 years to fund the on AIDS vaccine research published by the International AIDS has never looked more promising. A research and development of new vac- Vaccine Initiative (IAVI). It is currently available in English, French, Spanish, and Portuguese as a downloadable PDF file report released last year by the World cines, and distribution of existing vac- or an e-mail bulletin. Health Organization (WHO), the World cines to people in the world’s poorest IAVI is a global not-for-profit organization working to speed the Bank, and the United Nations Children’s countries. search for a vaccine to prevent HIV infection and AIDS. Founded in 1996 and operational in 25 countries, IAVI and its network Fund (UNICEF), declared that the last US President Barack Obama and his of partners research and develop vaccine candidates. IAVI also 10 years were the most productive ever administration have also placed advocates for a vaccine to be a global priority and works to assure that a future vaccine will be accessible in the history of vaccine development. renewed emphasis on vaccine develop- to all who need it. For more information, Then, in January, at the World Economic ment. In a memo circulated in May, the go to www.iavi.org. Forum’s annual meeting in Davos, Swit- Obama administration mentioned Printed with soy-based ink on FSC-certified paper. zerland, the Bill & Melinda Gates Foun- “seeking and then scaling up potential Copyright 2010. dation announced they were committing game-changers, such as vaccines,” as a

2 VAX MAY 2010 | WWW.IAVIREPORT.ORG way to solve longstanding challenges the world’s poorest people. tion can cause, most seriously, anemia such as poverty. A number of scientists at the recent and iron deficiency due to severe blood While global health organizations and vaccine conference are hoping the loss. Prolonged, untreated hookworm many public health researchers say vac- emphasis on vaccines as a way to com- infections can also result in mental cines are one of the most cost-effective bat poverty will translate into increased retardation. ways of saving children’s lives and reduc- funding for vaccine research and devel- The Sabin Institute is also hoping to ing poverty, the WHO estimates that only opment. Though NTDs receive much begin clinical trials of a vaccine candi- about 18% of the $6 billion annual global less treatment and prevention funding date against schistosomiasis, another vaccine market is spent in developing than HIV/AIDS, tuberculosis, and parasitic disease which infects approxi- countries, a point underscored at the 13th malaria, they have devastating conse- mately 207 million people worldwide, Annual Conference on Vaccine Research, quences on maternal and child health, most of them in Africa. Both the Sabin which took place in Bethesda, Maryland and may increase susceptibility to HIV/ Institute and the Institut Pasteur in from April 26-28. AIDS and malaria or worsen disease France are developing vaccines against The 400 researchers and public health progression in those already infected. two different parasites that trigger schis- workers who gathered at the meeting, tosomiasis. The vaccines would be used which was organized by the National along with drug treatment to reduce or Foundation for Infectious Diseases, delay disease progression. emphasized how difficult vaccine discov- Schistosomiasis is referred to as snail ery and distribution can be. Vaccines fever because the parasitic worms that typically take many years and a hefty spread the disease live in snails. People investment of between $200 million and become infected when they come in con- $500 million to develop, noted Don tact with fresh water contaminated by the Francis, founder of the nonprofit organi- parasites that the snails excrete. The zation Global Solutions for Infectious worms grow inside a person’s blood ves- Diseases, during his keynote speech. And sels and produce eggs, which then travel even when vaccines do get licensed, it can to the intestines or bladder. Like hook- take decades until the disease is eradi- worm, repeated bouts of schistosomiasis cated because of the logistical difficulties can cause anemia and malnutrition. In and expenses involved in distributing rare instances, the eggs can be found in vaccines on a global scale. Although the the brain or spinal cord, causing brain first polio vaccine was licensed in 1955, it damage and paralysis. took 36 years for the virus to be eradi- “NTDs impair intellectual and phys- More effort is also being given to con- cated in North America, and 50 years for ical development in children, cause trol of foot-and-mouth disease, a highly it to be eradicated in all but four coun- adverse pregnancy outcomes, and contagious disease of cattle, buffalo, tries where it is still endemic, Francis reduce worker productivity,” said Peter sheep, and pigs. The disease rarely affects noted. Hotez, chairman of microbiology, humans, but the speed in which it spreads Despite these obstacles, vaccine immunology, and tropical medicine at through livestock can seriously reduce researchers are increasingly focusing on George Washington University Medical milk and meat production, and the trade the link between poverty and disease, and Center in Washington, DC. bans that result after outbreaks seriously the conference opened with an array of A number of vaccine candidates affect the economies of food-exporting talks about the vital role human and ani- against NTDs, so-called anti-poverty nations. mal vaccines can play in reducing poverty vaccines, are in the clinical pipeline. Researchers are excited about a novel and in strengthening economic and politi- Hotez, who also heads up The Sabin livestock vaccine for foot-and-mouth cal security, particularly in developing Vaccine Institute, said they are hoping disease developed by researcher Martin countries. to soon begin a Phase IIb test-of-concept Grubman at the Plum Island Animal One area of focus is scaling up distri- trial in Brazil of a vaccine candidate Research Center in New York in collab- bution of the recently licensed vaccines against hookworm, a parasitic worm oration with the US Department of against rotavirus, which causes diarrheal that lives in the small intestine and Homeland Security and GenVec, a bio- disease, and pneumococcal bacteria, infects about 576 million people, mostly pharmaceutical company in Maryland. which cause pneumonia, in developing in developing countries. Hookworm Luis Rodriguez, research leader at the countries, where the death rate from infection typically occurs when the lar- Plum Island Animal Research Center, these infections is highest. There is also vae from hookworm eggs penetrate a said studies of the vaccine candidate more attention being given to an array of person’s skin. The larvae eventually showed it was able to prevent clinical 13 so-called neglected tropical diseases latch onto the intestinal wall, where disease in cattle when they were chal- (NTDs) that cause about 530,000 deaths they mature into adult hookworms and lenged with the virus that causes foot- annually and afflict about one billion of produce more eggs. Hookworm infec- and-mouth disease. g

WWW.IAVIREPORT.ORG | VAX MAY 2010 3 [PRIMER] Understanding if Broadly Neutralizing Antibodies are the Answer Researchers are pursuing multiple paths to determine if antibodies can block HIV infection By Regina McEnery Antibodies are Y-shaped proteins that However, this is a difficult task and it may studying individuals who although work primarily by latching onto viruses take some time before vaccine candidates repeatedly exposed to HIV, seem to be and preventing them from infecting target based on these bNAbs are ready for clinical able to ward off infection. Although it cells. Antibodies are induced by most, if not testing. Until then, researchers are also con- has been suggested that antibodies may all, existing vaccines and are thought to ducting other studies in animals and be what protects these individuals from play a crucial role in the protection these humans to try to determine whether these infection, in these cases, it is difficult to vaccines afford. bNAbs will be capable of blocking HIV draw firm conclusions. While it is still unclear precisely what infection. Another way researchers are attempting types of immune responses will need to be to learn if bNAbs can protect against HIV triggered by a vaccine to protect against Protection in animals is by studying the passive transfer of mater- HIV infection, many scientists believe There is evidence from studies in ani- nal antibodies. Pregnant women pass anti- that an AIDS vaccine will need to induce mals to suggest that if scientists could learn bodies to their fetuses through the pla- antibodies (see VAX February 2007 how to induce bNAbs against HIV through centa. If the mother is HIV infected, she Primer on Understanding Neutralizing a vaccine, they might be able to block infec- may also pass HIV-specific antibodies to Antibodies). And because HIV is an tion. To evaluate this, researchers conduct her fetus. incredibly diverse virus, with multiple what are referred to as passive immuniza- In a study of 100 infants born to HIV- clades or serotypes in circulation around tion studies. In these studies, researchers infected mothers, researchers found that the world, researchers are focusing on inject bNAbs directly into animals and although the mothers had indeed trans- developing vaccine candidates that can then purposely expose them to either HIV, ferred HIV-specific neutralizing antibodies induce antibodies that are capable of or a hybrid virus known as SHIV that is a to the infants, there was no evidence that blocking or neutralizing many circulating combination of HIV and simian immuno- these antibodies actually protected the HIV strains, so-called broadly neutraliz- deficiency virus, the monkey form of HIV. infants against HIV infection during the ing antibodies (bNAbs). In studies with one of the bNAbs known breast-feeding period. While this suggests Such bNAbs against HIV exist. The as b12, scientists found that this antibody that these antibodies were not effective at immune systems of individuals who are was able to block HIV infection in mice blocking HIV, it does not mean that some naturally infected with HIV generate that were genetically altered to have human of the newer, more potent bNAbs would antibodies against the virus, some of immune cells. In some studies, non-human not be effective. which are broadly neutralizing. By screen- primates passively immunized with b12 To determine this, researchers are con- ing blood samples from HIV-infected were completely protected against infection sidering conducting a clinical trial of pas- individuals, researchers have been able to when they were purposely exposed to sive in HIV-uninfected peo- isolate several bNAbs. Just recently, eight SHIV. While in other studies, infection of ple. This type of study would show new bNAbs were discovered, some of b12-immunized monkeys was delayed whether directly administering one or which are more potent than those previ- compared to those that were not immu- more of the more potent, recently discov- ously identified (see VAX March 2010 nized with b12. ered bNAbs into HIV-uninfected individ- Primer on Understanding Advances in Researchers are now planning to do uals through injection would protect the Search for Antibodies Against HIV). similar studies in non-human primates them against HIV if they were naturally Researchers are now studying these with some of the newly discovered, more exposed to the virus. bNAbs and using them to potent bNAbs to see how well they can Scientists are also hoping to conduct a design vaccine candi- protect against infection in animal models. clinical trial soon to evaluate another anti- dates that would body strategy, known as gene transfer, to ideally be able to Evidence for protection in humans see if it can protect against HIV infection i nduce t hese Although these passive immunization (see VAX November 2008 Primer on antibodies in studies in mice and non-human primates Understanding Approaches to Inducing people before provide some evidence that bNAbs can Neutralizing Antibodies). Rather than they are exposed block HIV infection from occurring, there directly injecting bNAbs, the gene transfer to HIV, thereby is little evidence that this is also true in approach involves introducing the genes protecting them humans. that could make the bNAbs into HIV-unin- against infection. For many years, researchers have been fected people. g

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