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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Vesicular stomatitis virus-simian retrovirus type 2 vaccine protects macaques from detectable infection and B-cell
Rajeev Gautam1, Arun Iyer, Meredith Hunter
1Division of Microbiology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA.
Abstract:
Natural infection with simian retrovirus (SRV) has long been recognized in rhesus macaques (RMs) and may result in an AIDS-like disease. Importantly, SRV infections persist as a problem in recently imported macaques. Therefore, there is a clear need to control SRV spread in macaque colonies. We developed a recombinant vesicular stomatitis virus (VSV)-SRV vaccine consisting of replication-competent hybrid VSVs that express SRV gag and env in separate vectors. The goal of this study was to assess the immunogenicity and protective efficacy of the VSV-SRV serotype 2 vaccine prime-boost approach in RMs. The VSV-SRV vector (expressing either SRV gag or env) vaccines were intranasally administered in 4 RMs, followed by a boost 1 month after the first vaccination. Four RMs served as controls and received the VSV vector alone. Two months after the boost, all animals were intravenously challenged with SRV-2 and monitored for 90 days. After the SRV-2 challenge, all four controls became infected, and viral loads (VLs) ranged from 10(6) to 10(8) SRV RNA copies/ml of plasma. Two animals in the control group developed simian AIDS within 7 to 8 weeks postinfection and were euthanized. Anemia and weight loss were observed in the remaining controls. During acute infection, severe B-cell depletion and no significant changes in T-cell population were observed in the control group. Control RMs with greater preservation of B cells and lower VLs survived longer. SRV-2 was undetectable in vaccinated animals, which remained healthy, with no clinical or biological signs of infection and preservation of B cells. Our study showed that the VSV-SRV vaccine is a strong approach for preventing clinically relevant type D retrovirus infection and disease in RMs, with protection of 4/4 RMs from SRV infection and prevention of B-cell destruction. B-cell protection was the strongest correlate of the long-term survival of all vaccinated and control RMs.
Insights
A new recombinant vesicular stomatitis virus (VSV)-simian retrovirus (SRV) vaccine effectively prevented SRV-2 infection and simian AIDS in rhesus macaques. Vaccinated macaques remained healthy, showing preserved B cells, unlike unvaccinated controls.
Area of Science:
- Veterinary Virology
- Immunology
- Primate Health
Background:
- Simian retrovirus (SRV) infection causes AIDS-like disease in rhesus macaques (RMs), posing a significant challenge in macaque colonies.
- SRV infections are a persistent issue, particularly in recently imported macaques, necessitating effective control strategies.
Purpose of the Study:
- To evaluate the immunogenicity and protective efficacy of a novel recombinant vesicular stomatitis virus (VSV)-SRV vaccine in rhesus macaques.
- To assess the prime-boost vaccination strategy using VSV vectors expressing SRV gag and env against SRV-2 challenge.
Main Methods:
- Developed replication-competent hybrid VSV vectors expressing SRV gag and env.
- Intranasal administration of VSV-SRV vaccines (gag or env) followed by a boost vaccination in RMs.
- Intravenous challenge with SRV-2 in vaccinated and control RMs, followed by 90-day monitoring of clinical signs, viral loads, and immune cell populations.
Main Results:
- All four control RMs became infected with SRV-2, exhibiting high viral loads and developing simian AIDS, anemia, or weight loss.
- Vaccinated RMs showed no detectable SRV-2, remained clinically healthy, and maintained B-cell populations.
- Preservation of B cells correlated with longer survival in control animals, highlighting their importance in controlling SRV infection.
Conclusions:
- The VSV-SRV vaccine is a promising approach for preventing SRV infection and associated diseases in rhesus macaques.
- The vaccine demonstrated 100% protection against SRV infection and prevented the critical B-cell depletion observed in controls.
- B-cell preservation emerged as a key indicator of successful SRV control and long-term survival.
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