Vaccine-induced immune responses against both Gag and Env improve control of simian immunodeficiency virus replication in rectally challenged rhesus macaques.

TitleVaccine-induced immune responses against both Gag and Env improve control of simian immunodeficiency virus replication in rectally challenged rhesus macaques.
Publication TypeJournal Article
Year of Publication2017
AuthorsMartins MA, Shin YC, Gonzalez-Nieto L, Domingues A, Gutman MJ, Maxwell HS, Castro I, Magnani DM, Ricciardi M, PedreƱo-Lopez N, Bailey V, Betancourt D, Altman JD, Pauthner M, Burton DR, von Bredow B, Evans DT, Yuan M, Parks CL, Ejima K, Allison DB, Rakasz E, Barber GN, Capuano S, Lifson JD, Desrosiers RC, Watkins DI
JournalPLoS Pathog
Volume13
Issue7
Paginatione1006529
Date Published07/21/2017
ISSN1553-7374
KeywordsAnimals, Antibodies, Viral, Disease Models, Animal, env Gene Products, Human Immunodeficiency Virus, gag Gene Products, Human Immunodeficiency Virus, HIV Infections, HIV-1, Humans, Macaca mulatta, Rectum, SAIDS Vaccines, Simian Acquired Immunodeficiency Syndrome, Simian immunodeficiency virus, Virus Replication
Abstract

The ability to control lentivirus replication may be determined, in part, by the extent to which individual viral proteins are targeted by the immune system. Consequently, defining the antigens that elicit the most protective immune responses may facilitate the design of effective HIV-1 vaccines. Here we vaccinated four groups of rhesus macaques with a heterologous vector prime/boost/boost/boost (PBBB) regimen expressing the following simian immunodeficiency virus (SIV) genes: env, gag, vif, rev, tat, and nef (Group 1); env, vif, rev, tat, and nef (Group 2); gag, vif, rev, tat, and nef (Group 3); or vif, rev, tat, and nef (Group 4). Following repeated intrarectal challenges with a marginal dose of the neutralization-resistant SIVmac239 clone, vaccinees in Groups 1-3 became infected at similar rates compared to control animals. Unexpectedly, vaccinees in Group 4 became infected at a slower pace than the other animals, although this difference was not statistically significant. Group 1 exhibited the best post-acquisition virologic control of SIV infection, with significant reductions in both peak and chronic phase viremia. Indeed, 5/8 Group 1 vaccinees had viral loads of less than 2,000 vRNA copies/mL of plasma in the chronic phase. Vaccine regimens that did not contain gag (Group 2), env (Group 3), or both of these inserts (Group 4) were largely ineffective at decreasing viremia. Thus, vaccine-induced immune responses against both Gag and Env appeared to maximize control of immunodeficiency virus replication. Collectively, these findings are relevant for HIV-1 vaccine design as they provide additional insights into which of the lentiviral proteins might serve as the best vaccine immunogens.

DOI10.1371/journal.ppat.1006529
Alternate JournalPLoS Pathog.
PubMed ID28732035
PubMed Central IDPMC5540612
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
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