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

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. He...

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Bibliographic Details
Published in:PLoS pathogens 2017-07, Vol.13 (7), p.e1006529
Main Authors: Martins, Mauricio A, Shin, Young C, Gonzalez-Nieto, Lucas, Domingues, Aline, Gutman, Martin J, Maxwell, Helen S, Castro, Iris, Magnani, Diogo M, Ricciardi, Michael, Pedreño-Lopez, Nuria, Bailey, Varian, Betancourt, Dillon, Altman, John D, Pauthner, Matthias, Burton, Dennis R, von Bredow, Benjamin, Evans, David T, Yuan, Maoli, Parks, Christopher L, Ejima, Keisuke, Allison, David B, Rakasz, Eva, Barber, Glen N, Capuano, 3rd, Saverio, Lifson, Jeffrey D, Desrosiers, Ronald C, Watkins, David I
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
AIDS vaccines
Animals
Antibodies, Viral - immunology
Antigens
Biology and life sciences
Chronic infection
Control
Disease Models, Animal
env Gene Products, Human Immunodeficiency Virus - genetics
env Gene Products, Human Immunodeficiency Virus - immunology
Funding
gag Gene Products, Human Immunodeficiency Virus - genetics
gag Gene Products, Human Immunodeficiency Virus - immunology
Gag protein
Genetic aspects
HIV
HIV Infections - immunology
HIV Infections - virology
HIV-1 - genetics
HIV-1 - immunology
HIV-1 - physiology
Human immunodeficiency virus
Humans
Immune response
Immune system
Immunology
Inserts
Laboratories
Macaca mulatta
Medical research
Medicine and Health Sciences
Monkeys & apes
Nef protein
Neutralization
Pathology
Primates
Proteins
Rectum - immunology
Rectum - virology
Replication
Rhesus monkey
SAIDS Vaccines - administration & dosage
SAIDS Vaccines - genetics
SAIDS Vaccines - immunology
Simian Acquired Immunodeficiency Syndrome - immunology
Simian Acquired Immunodeficiency Syndrome - virology
Simian immunodeficiency virus
Simian Immunodeficiency Virus - genetics
Simian Immunodeficiency Virus - immunology
Stability
Statistical analysis
Supervision
Tat protein
Vaccines
Viremia
Virus Replication
Viruses
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1006529