Toward an AIDS vaccine: lessons from natural simian immunodeficiency virus infections of African nonhuman primate hosts

Abstract

The design of an effective AIDS vaccine has eluded the efforts of the scientific community to the point that alternative approaches to classic vaccine formulations have to be considered. We propose here that HIV vaccine research could greatly benefit from the study of natural simian immunodeficiency virus (SIV) infections of African nonhuman primates. Natural SIV hosts (for example, sooty mangabeys, African green monkeys and mandrills) share many features of HIV infection of humans; however, they usually do not develop immunodeficiency. These natural, nonprogressive SIV infections represent an evolutionary adaptation that allows a peaceful coexistence of primate lentiviruses and the host immune system. This adaptation does not result in reduced viral replication but, rather, involves phenotypic changes to CD4+ T cell subsets, limited immune activation and preserved mucosal immunity, all of which contribute to the avoidance of disease progression and, possibly, to the reduction of vertical SIV transmission. Here we summarize the current understanding of SIV infection of African nonhuman primates and discuss how unraveling these evolutionary adaptations may provide clues for new vaccine designs that might induce effective immune responses without the harmful consequences of excessive immune activation.

Immune responses during spontaneous control of HIV and AIDS: what is the hope for a cure?

“…Protection against AIDS in natural hosts occurs despite viral replication in the blood and gut at levels similar to or higher than in HIV-1-infected humans and SIVmac-infected macaques [46]. Protection is associated with an absence of both chronic T cell activation and chronic inflammation [45,47]. The studies in natural hosts have contributed to the increased consideration of the major role of chronic immune activation in the development of AIDS.…”

Application of PCR Technologies to Humans, Animals, Plants and Pathogens from Central Africa

“…However, when the scientific community is reflecting on how simian immunodeficiency virus infections hosted by African nonhuman primates could help in designing an AIDS vaccine for example, Central African scientists are absent [118]. This situation should change and African institutions, supported by their government, should advocate strongly for and invest in an African AIDS vaccine.…”

HIV Without AIDS: The Immunological Secrets of Natural Hosts

“…Studies aimed at characterizing the virus-host interactions in natural hosts have led to important findings for understanding HIV pathogenesis in humans and, even more important, have many implications for new therapies and vaccines, giving us the opportunity to stop disease progression by understanding what nature has already discovered over millennia (Sodora et al, 2009). Table 2, along with the section above, summarizes several therapeutic approaches that could attempt to mimic the critical features of nonpathogenic infection in sooty mangabeys, which could be beneficial if included in the clinical management of HIV-infected humans.…”