Norman L. Letvin
Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
It has been apparent for many years that vaccination of nonhuman primates with a variety of immunogens cannot protect from infection with pathogenic immunodeficiency viruses, but vaccinated animals have demonstrated a delay in disease progression and prolonged survival following viral challenge. Recent technical advances have facilitated a thorough evaluation of this phenomenon. These advances include the development of immunodeficiency viruses that result in reproducible levels of viral replication and CD4+ T lymphocyte loss and death in monkeys, as well as the development of techniques to quantitate virus-specific cytotoxic T-lymphocyte responses and plasma viral RNA in these species. Studies employing these tools have recently shown that monkeys receiving vaccines that elicit cytotoxic T-lymphocyte responses that are then infected with immunodeficiency viruses have low virus loads and, accordingly, slow disease progression. This type of clinical protection has been seen against infection with pathogenic chimeric simian-human immunodeficiency viruses and simian immunodeficiency viruses. Vaccine modalities that have resulted in this type of protection in monkeys include plasmid DNA and recombinant live viral vectors, such as pox viruses and gene-deleted adenoviruses. Since at least some of these vaccine technologies should be effective in eliciting this level of immunity in humans, there is reason to suppose that available immunogens could confer comparable clinical benefit in humans. Thus, vaccinated individuals who subsequently become infected with HIV may have lower viral burdens and a longer survival following infection than those who are unvaccinated. Moreover, with lower viral burdens in their secretions, vaccines may have a reduced likelihood of transmitting virus to uninfected individuals. Therefore, while our ultimate goal remains the creation of vaccines that confer sterilizing immunity against HIV, currently available vaccine technologies may be capable of providing substantial clinical benefit in humans. Contact Author about this Abstract
