The Potential of Immune Modulation in Therapeutic HIV-1 Vaccination

Seddiki, Nabila; Picard, Florence; Dupaty, Léa; Lévy, Yves; Godot, Véronique

doi:10.3390/vaccines8030419

Cited by 2 publications

(1 citation statement)

References 104 publications

(113 reference statements)

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“…Recently, many investigators have turned to the use of immunotherapeutic agents which could, in combination with vaccines, improve the ability of CD8 T cells to target and destroy infected cells during HIV/SIV infection (11). One such class of immunotherapeutic agents that can boost the CD8 T cell response to HIV/SIV is interleukin-15 (IL-15) agonists (12, 13).…”

Section: Introductionmentioning

confidence: 99%

Control of SIV infection in prophylactically vaccinated, ART-naïve macaques is required for the most efficacious CD8 T cell response during treatment with the IL-15 superagonist N-803

Ellis-Connell

Balgeman

Harwood

et al. 2022

Preprint

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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-naïve, SIV+ 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 N-803 mediated suppression of SIV plasma viremia. We 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. Animals were then intravenously infected with SIVmac239M. Six months after infection, animals were treated with N-803. We found no differences in control of plasma viremia during N-803 treatment between vaccinated and unvaccinated macaques. Furthermore, the SIV-specific CD8 T cells displayed no differences in frequency or ability to traffic to the lymph nodes. Interestingly, when we divided the SIV+ animals based on plasma viral load set-point prior to N-803 treatment, N-803 increased the frequency of SIV-specific T cells expressing ki-67+ and granzyme B+ in animals with low plasma viremia (<104 copies/mL; SIV controllers) compared to animals with high plasma viremia (>104 copies/mL;SIV non-controllers). In addition, Gag-specific CD8 T cells from the SIV+ controllers had a greater increase in CD107a+CD8+ T cells when compared to SIV+ non-controllers. Overall, our results indicate that N-803 is most effective in SIV+ animals with a pre-existing immunological ability to control SIV replication.

show abstract

Section: Introductionmentioning

confidence: 99%

Control of SIV infection in prophylactically vaccinated, ART-naïve macaques is required for the most efficacious CD8 T cell response during treatment with the IL-15 superagonist N-803

Ellis-Connell

Balgeman

Harwood

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

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

Ellis-Connell

Balgeman

Harwood

et al. 2022

J Virol

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N-803 is a drug that boosts the immune cells involved in combating HIV/SIV infection. Here, we found that in SIV + 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.

show abstract

The Potential of Immune Modulation in Therapeutic HIV-1 Vaccination

Cited by 2 publications

References 104 publications

Control of SIV infection in prophylactically vaccinated, ART-naïve macaques is required for the most efficacious CD8 T cell response during treatment with the IL-15 superagonist N-803

Control of SIV infection in prophylactically vaccinated, ART-naïve macaques is required for the most efficacious CD8 T cell response during treatment with the IL-15 superagonist N-803

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

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