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Vaccines and Immunotherapies for the Prevention of Infectious Diseases Having Cutaneous Manifestations

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Vaccines and Immunotherapies for the Prevention of Infectious Diseases Having Cutaneous Manifestations CONTINUING MEDICAL EDUCATION Vaccines and immunotherapies for the prevention of infectious diseases having cutaneous manifestations Jashin J. Wu, MD,a David B. Huang, MD, MPH,b Katie R. Pang, MD,a and Stephen K. Tyring, MD, PhD, MBAc Houston, Texas Although the development of antimicrobial drugs has advanced rapidly in the past several years, such agents act against only certain groups of microbes and are associated with increasing rates of resistance. These limitations of treatment force physicians to continue to rely on prevention, which is more effective and cost-effective than therapy. From the use of the smallpox vaccine by Jenner in the 1700s to the current concerns about biologic warfare, the technology for vaccine development has seen numerous advances. The currently available vaccines for viral illnesses include Dryvax for smallpox; the combination measles, mumps, and rubella vaccine; inactivated vaccine for hepatitis A; plasma-derived vaccine for hepatitis B; and the live attenuated Oka strain vaccine for varicella zoster. Vaccines available against bacterial illnesses include those for anthrax, Haemophilus influenzae, and Neisseria meningitidis. Currently in development for both prophylactic and therapeutic purposes are vaccines for HIV, herpes simplex virus, and human papillomavirus. Other vaccines being investigated for prevention are those for cytomegalovirus, respiratory syncytial virus, parainfluenza virus, hepatitis C, and dengue fever, among many others. Fungal and protozoan diseases are also subjects of vaccine research. Among immunoglobulins approved for prophy- lactic and therapeutic use are those against cytomegalovirus, hepatitis A and B, measles, rabies, and tetanus. With this progress, it is hoped that effective vaccines soon will be developed for many more infectious diseases with cutaneous manifestations. (J Am Acad Dermatol 2004;50:495-528.) Learning objective: At the completion of this learning activity, participants should be familiar with the current and experimental vaccines and immunotherapies for infectious diseases with cutaneous manifes- tations. he medical approach to infectious diseases is fraught with limitations. Antimicrobial drugs are available for only a few groups of mi- From the Center for Clinical Studiesa; Department of Internal T crobes. These drugs provide no cure for infections Medicine, Division of Infectious Diseases, Baylor College of such as HIV or herpes simplex virus (HSV) but Medicineb; and Departments of Dermatology, Microbiology- Immunology, and Internal Medicine, University of Texas merely alter the clinical course of disease while the Medical Branch.c medication is being taken. Because of the void of Funding sources: None. adequate antimicrobial treatment, the prevention of Disclosure: Dr Tyring has conducted research on vaccines for vesic- these infections is all the more crucial. ular stomatitis virus, herpes simplex virus, human papillomavi- Vaccination, with public health measures, is the ruses, and HIV with grants from Merck, Chiron, GlaxoSmithKline, MedImmune, and VaxGen to the University of Texas Medical best option for controlling the spread of infectious Branch and the Center for Clinical Studies. diseases. Vaccination is ranked as the greatest Presented in part at the 61st Annual Meeting of the American Acad- public health achievement in the last century, con- emy of Dermatology, San Francisco, California, March 21, 2003. tributing the most to decreased global morbidity Also presented in part at the 62nd Annual Meeting of the Amer- and mortality.1,2 Since 1988 more than 2 billion ican Academy of Dermatology, Washington, DC, February 6-11, 2004. children have been immunized, saving more than Reprint requests: Stephen K. Tyring, MD, PhD, MBA, Professor of 3 million pediatric lives per year.3 The significant Dermatology, University of Texas Health Science Center, impact of immunization is well illustrated by the Houston, 2060 Space Park Dr, Ste 200, Houston, TX 77058. E-mail: complete eradication of smallpox in 1977. Global [email protected]. 0190-9622/$30.00 eradication of poliomyelitis is currently under © 2004 by the American Academy of Dermatology, Inc. way, and although the goal of total elimination of doi:10.1016/j.jaad.2003.12.003 this disease by the end of 2000 unfortunately was 495 496 Wu et al JAM ACAD DERMATOL APRIL 2004 Table I. Timeline of vaccine development* Abbreviations used: 1796—Smallpox AVA: anthrax vaccine adsorbed CDC: Centers for Disease Control and 1800 1881—Anthrax Prevention 1885—Rabies CRM197: cross-reacting, mutant, nontoxic 1900 1945—Influenza diphtheria toxin 1953—Yellow fever DTaP: diphtheria and tetanus toxoids and acellular pertussis vaccine 1963—IPV, OPV (Poliomyelitis) DTP: diphtheria and tetanus toxoids and 1963—Measles whole-cell pertussis vaccine 1967—Mumps HbOC: Haemophilus influenzae type b 1969—Rubella (polyribosyl ribitol phosphate) 1975—Neisseria meningitidis oligosaccharides conjugated to CRM197 HBsAg: hepatitis B surface antigen 1980—Adenovirus Hib: Haemophilus influenzae type b 1980—Rabies (IMOVAX: first FDA-approved HPV: human papillomavirus rabies vaccine) HSV: herpes simplex virus 1981—Hepatitis B IVIG: intravenous immunoglobulin LACK: Leishmania homologue of receptors for 1987—Haemophilus influenzae activated C kinase 1992—Japanese encephalitis MMR: measles-mumps-rubella 1992—DTaP (diphtheria-tetanus-acellular OspA: 31-kd outer-surface protein pertussis) OspC: 23-kd outer-surface protein 1995—Hepatitis A, Varicella PA: protective antigen † PGA: poly-␥-linked D-glutamic acid 1998—Lyme disease PRP: polyribosyl ribitol phosphate 1998—Rotavirus† PRP-D: polyribosyl ribitol phosphate conjugated 2000 2000—Streptococcus pneumoniae to diphtheria toxoid 2000—Dryvax (smallpox) PRP-OMP: polyribosyl ribitol phosphate conjugated to an outer-membrane protein complex 2002—Pediarix (DTaP-HepB-IPV) rOspA: recombinant 31-kd outer-surface protein SSPE: subacute sclerosing panencephalitis *Dates for smallpox, anthrax, and rabies vaccines are of the first pub- VIG: vaccinia immunoglobulin lished results of vaccine usage. Remaining dates are those of ap- VLP: virus-like particles proval of vaccines by the Food and Drug Administration (FDA). †No longer available. CURRENTLY LICENSED VACCINES Viruses not met,4 the eradication is estimated to be com- Smallpox. In 1796 Edward Jenner first demon- plete by 2005.5 A number of other vaccines have strated that inoculation of cowpox virus into human led to notable decreases in infections and compli- skin could lead to protection from subsequent small- cations. For instance, after years of widespread pox infection.8 He named the inoculation substance measles vaccination, a record low of 37 measles vaccine, based on the Latin word vacca, meaning cases was reported in the United States in 2002.6 cow. The most recent vaccines used for smallpox Vaccines for Haemophilus influenzae and Neisse- vaccination were derived from a species similar to ria meningitidis have greatly decreased the inci- cowpox, called vaccinia virus. Vaccinia virus is a dence of these diseases. These currently available member of the orthopox virus family, which in- vaccines also provide a basic framework of cludes variola virus, the virus that causes smallpox, knowledge and experience with which other vac- and other viruses such as cowpox and monkeypox. cines can be developed. Several strains of the live attenuated virus vaccine Unfortunately, the progress in finding new vac- were employed in the eradication of disease. The cines cannot be rapid enough. The incidence of smallpox vaccine has been the prototype of success many viral infections, such as HIV, HSV, and hu- of a viral vaccine. Prior to immunization, smallpox man papillomaviruses (HPVs), is increasing de- infection relentlessly killed hundreds of millions of spite the currently available antiviral agents. The persons. The complete eradication of this disease development of prospective vaccines is generally could easily be considered the greatest success story measured in decades (Table I), marked by small in medical history. increments of advancement before the final prod- Vaccine production ended 2 decades ago after uct becomes available.7 Numerous different vac- the eradication of smallpox,9 and approximately 60 cine candidates often are developed and evalu- million vaccine doses remain worldwide.10 Because ated over many years before a single effective of recent concerns over potential biologic warfare in vaccine is licensed. the future, the threat of smallpox may not have been JAM ACAD DERMATOL Wu et al 497 VOLUME 50, NUMBER 4 completely eliminated with eradication of the dis- ease. Therefore, renewed interest in the production of smallpox vaccines has developed. The destruction of the 2 remaining smallpox virus reserves, in Atlanta and Moscow, has been a source of ongoing debate. Opponents of destruction con- tend that the virus stocks would be helpful for future research, such as smallpox pathogenesis and the production of new antiviral agents.11,12 Proponents argue that the virus genome has already been cloned and sequenced and is unnecessary for such re- search.13 The World Health Assembly in May 1999 Fig 1. Ocular vaccinia secondary to digital spread from resolved to postpone the previously arranged small- the inoculation site. pox destruction scheduled for June 30 of that year.14 All US smallpox vaccine formulations contain the New York City Board of Health vaccinia strain, The CDC is holding the other 3 vaccines in re- which is less reactogenic than other strains.15
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