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Control of Simian Immunodeficiency Virus Infection in Prophylactically Vaccinated, Antiretroviral Treatment-Naive Macaques Is Required for the Most Efficacious CD8 T Cell Response during Treatment with the Interleukin-15 Superagonist N-803.
- Source :
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Journal of virology [J Virol] 2022 Oct 26; Vol. 96 (20), pp. e0118522. Date of Electronic Publication: 2022 Oct 03. - Publication Year :
- 2022
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Abstract
- The IL-15 superagonist N-803 has been shown to enhance the function of CD8 T cells and NK cells. We previously found that in a subset of vaccinated, ART-naive, SIV <superscript>+</superscript> rhesus macaques, N-803 treatment led to a rapid but transient decline in plasma viremia that positively correlated with an increase in the frequency of CD8 T cells. Here, we tested the hypothesis that prophylactic vaccination was required for the N-803 mediated suppression of SIV plasma viremia. We either vaccinated rhesus macaques with a DNA prime/Ad5 boost regimen using vectors expressing SIVmac239 gag with or without a plasmid expressing IL-12 or left them unvaccinated. The animals were then intravenously infected with SIVmac239M. 6 months after infection, the animals were treated with N-803. We found no differences in the control of plasma viremia during N-803 treatment between vaccinated and unvaccinated macaques. Interestingly, when we divided the SIV <superscript>+</superscript> animals based on their plasma viral load set-points prior to the N-803 treatment, N-803 increased the frequency of SIV-specific T cells expressing ki-67 <superscript>+</superscript> and granzyme B <superscript>+</superscript> in animals with low plasma viremia (<10 <superscript>4</superscript> copies/mL; SIV controllers) compared to animals with high plasma viremia (>10 <superscript>4</superscript> copies/mL; SIV noncontrollers). In addition, Gag-specific CD8 T cells from the SIV <superscript>+</superscript> controllers had a greater increase in CD8 <superscript>+</superscript> CD107a <superscript>+</superscript> T cells in ex vivo functional assays than did the SIV <superscript>+</superscript> noncontrollers. Overall, our results indicate that N-803 is most effective in SIV <superscript>+</superscript> animals with a preexisting immunological ability to control SIV replication. IMPORTANCE N-803 is a drug that boosts the immune cells involved in combating HIV/SIV infection. Here, we found that in SIV <superscript>+</superscript> rhesus macaques that were not on antiretroviral therapy, N-803 increased the proliferation and potential capacity for killing of the SIV-specific immune cells to a greater degree in animals that spontaneously controlled SIV than in animals that did not control SIV. Understanding the mechanism of how N-803 might function differently in individuals that control HIV/SIV (for example, individuals on antiretroviral therapy or spontaneous controllers) compared to settings where HIV/SIV are not controlled, could impact the efficacy of N-803 utilization in the field of HIV cure.
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 96
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 36190241
- Full Text :
- https://doi.org/10.1128/jvi.01185-22