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Updated: Jun 17, 2026
Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Multi-low-dose mucosal simian immunodeficiency virus SIVmac239 challenge of cynomolgus macaques immunized with
David O Willer1, Yongjun Guan, Mark A Luscher
1Department of Microbiology, Mt. Sinai Hospital, Ontario, Canada.
Abstract:
Hyperattenuated simian immunodeficiency virus SIVmac239-derived constructs Delta5-CMV and Delta6-CCI are an effort to render SIV incapable of, in practical terms, both reversion and recombination while maintaining the immune features of SIV as a retrovirus. Primary inoculation of cynomolgus macaques with 10(8) 50% tissue culture infective doses (TCID(50)) of Delta5-CMV or Delta6-CCI induced low-level humoral and cellular responses detectable in the absence of measureable in vivo replication. The first of three DNA boosts resulted in elevated gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) responses to Gag, Pol, and Env in the Delta5-CMV vaccine group compared to the Delta6-CCI vaccine group (P = 0.001). Weekly intrarectal challenge with a low dose of SIVmac239 followed by a dose escalation was conducted until all animals became infected. The mean peak viral load of the Delta5-CMV-vaccinated animals (3.7 x 10(5) copies/ml) was approximately 1 log unit lower than that of the control animals. More dramatically, the viral load set point of these animals was decreased by 3 log units compared to that of the controls (<50 versus 1.64 x 10(4) copies/ml; P < 0.0001). Seventy-five percent (6/8) of vaccine recipients controlled virus below 1,000 copies/ml for at least 6 months, with a subset controlling virus and maintaining substantial CD4 T-cell counts for close to 2 years of follow-up. The correlates of protection from SIV disease progression may lie in the rapidity and protective value of immune responses that occur early in primary SIV infection. Prior immunization with hyperattenuated SIVmac239, even if sterilizing immunity is not achieved, may allow a more advantageous host response.
Insights
Hyperattenuated simian immunodeficiency virus (SIV) vaccines, Delta5-CMV and Delta6-CCI, induced immune responses without replication. Vaccination with Delta5-CMV significantly reduced viral loads and improved control in macaques challenged with SIV.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Simian immunodeficiency virus (SIV) infection in macaques serves as a model for HIV research.
- Developing effective SIV vaccines is crucial for advancing HIV prevention strategies.
- Hyperattenuated SIV constructs aim to elicit immune responses without causing disease or replicating.
Purpose of the Study:
- To evaluate the immunogenicity and protective efficacy of two hyperattenuated SIVmac239-derived constructs, Delta5-CMV and Delta6-CCI, in a macaque model.
- To assess the ability of these vaccines to induce immune responses and control viral replication upon challenge.
- To investigate potential correlates of protection against SIV infection and disease progression.
Main Methods:
- Primary inoculation of cynomolgus macaques with hyperattenuated SIV constructs (Delta5-CMV or Delta6-CCI).
- Administration of DNA boosts to enhance immune responses.
- Intrarectal challenge with SIVmac239 with dose escalation until infection occurred.
- Monitoring of humoral and cellular immune responses (e.g., IFN-gamma ELISPOT) and viral loads (peak and set point).
Main Results:
- Both vaccine constructs induced detectable immune responses without measurable in vivo replication.
- Delta5-CMV vaccination led to significantly higher gamma interferon (IFN-gamma) ELISPOT responses compared to Delta6-CCI.
- Vaccinated animals exhibited approximately 1 log lower mean peak viral loads and a 3 log lower viral load set point compared to controls.
- A majority of vaccine recipients (75%) controlled virus below 1,000 copies/ml for at least 6 months, with some maintaining CD4+ T-cell counts for up to 2 years.
Conclusions:
- Hyperattenuated SIV immunization, even without achieving sterilizing immunity, can lead to significant control of viral replication and disease progression in macaques.
- Early immune responses elicited by vaccination appear critical for protection against SIV.
- These findings support the potential of hyperattenuated SIV vaccines as a strategy for controlling SIV/HIV infection.
