Immunology

(The Scientist, Vol:4, #22, pg. 20, November 12, 1990) (Copyright, The Scientist, Inc.) -------- R.C. Desrosiers, M.S. Wyand, T. Kodama, D.J. Ringler, et al., "Vaccine protection against simian immunodeficiency virus infection," Proceedings of the National Academy of Sciences, 86, 6353-57, August 1989. Ronald Desrosiers (New England Regional Primate Research Center, Harvard Medical School, Southborough, Mass.): "A vaccine would likely be of greatest public health benefit in stemming the increasing spread of AIDS. However, making a vaccine to protect against the AIDS virus, HIV, is probably going to be a very difficult task. The difficulties stem largely from the properties of the virus itself and the nature of the persistent infection. HIV, like other members of the lentiretrovirus subgroup, produces a long-term, persistent infection and chronic disease course in spite of an apparently strong host immune response to the infecting virus. Infected individuals may remain clinically well for years, maintaining high levels of humoral and cell-mediated immunity, only to succumb eventually to the virus. Thus, for a vaccine to be truly effective against the virus, it may have to protect absolutely against initial infection. This goes well beyond the expectations of currently used viral vaccines in humans, which mostly protect against acute disease caused by acute infections. In addition, there are a large number of non- or minimally cross-neutralizing HIV strain types; no one knows how many HIV strains would need to be included in a vaccine in order to provide broad protection against infection. In the case of poliovirus vaccines, three strain types provide broad protection against all existing poliovirus strains. "After a number of experimental failures from several laboratories, our study was the first to result in successful vaccine protection against AIDS virus infection. We used the closest known relative of HIV, a monkey virus called simian immunodeficiency virus (SIV), in an inactivated, killed form. It is important to remember that these vaccine protections were performed in a highly idealized, optimized laboratory setting. They were not meant to mimic the real-life situation, but instead were intended to show whether in principle a vaccine could afford protection under ideal conditions. The road to a safe, effective HIV vaccine for general human use promises to be a long and difficult one." J. Homsy, M. Meyer, M. Tateno, S. Clarkson, J.A. Levy, "The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells," Science, 244, 1357-60, 16 June 1989. Jay A. Levy (University of California, San Francisco): "This paper presented certain observations that merited the attention of scientists working in HIV infection. First, it provided further proof that antibodies bound to HIV particles could enhance virus infection of certain cells--in particular, peripheral blood macrophages, T cells, and even fibroblasts. Second, this paper indicated that this infection could take place independent of the CD4 molecule, which has been shown to be a major receptor molecule for HIV. Moreover, the results demonstrated that on the macrophage, the FcIIIR receptor mediated this enhancement of infection. The significance of these observations includes the fact that soluble CD4 therapy would not have any effect on blocking enhancement; that this phenomenon can be demonstrated with normal lymphocytes and macrophages, not just established cell lines; and that enhancing antibodies might be produced against the virus during immunization. In addition, the differential effect of enhancing antibodies on various virus strains further demonstrated the heterogeneity of HIV, suggesting that antibodies to one virus might enhance infection of another. Most importantly, the paper underlined the need to evaluate vaccine trials for the potential unwarranted production of enhancing antibodies." (The Scientist, Vol:4, Issue 22 pg 20, ) (Copyright, The Scientist, Inc.) WE WELCOME YOUR OPINION. IF YOU WOULD LIKE TO COMMENT ON THIS STORY, PLEASE WRITE TO US AT EITHER ONE OF THE FOLLOWING ADDRESSES: garfield@aurora.cis.upenn.edu 71764.2561@compuserve.com The Scientist, 3600 Market Street, Suite 450, Philadelphia, PA 19104 U.S.A.

Immunology

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