دورية أكاديمية
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.
| العنوان: | 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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| المؤلفون: | Ellis-Connell AL; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Balgeman AJ; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Harwood OE; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Moriarty RV; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA., Safrit JT; ImmunityBio, Culver City, California, USA., Weiler AM; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA., Friedrich TC; Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA., O'Connor SL; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA. |
| المصدر: | Journal of virology [J Virol] 2022 Oct 26; Vol. 96 (20), pp. e0118522. Date of Electronic Publication: 2022 Oct 03. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Society For Microbiology Original Publication: Baltimore, American Society for Microbiology. |
| مواضيع طبية MeSH: | Simian Immunodeficiency Virus* , Simian Acquired Immunodeficiency Syndrome* , HIV Infections*/drug therapy, Animals ; Macaca mulatta ; Interleukin-15/genetics ; Granzymes ; Viremia ; Ki-67 Antigen ; CD8-Positive T-Lymphocytes ; Anti-Retroviral Agents/therapeutic use ; Viral Load ; Interleukin-12 ; DNA |
| مستخلص: | 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 + 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 + 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 + and granzyme B + in animals with low plasma viremia (<10 4 copies/mL; SIV controllers) compared to animals with high plasma viremia (>10 4 copies/mL; SIV noncontrollers). In addition, Gag-specific CD8 T cells from the SIV + controllers had a greater increase in CD8 + CD107a + T cells in ex vivo functional assays than did the SIV + noncontrollers. Overall, our results indicate that N-803 is most effective in SIV + 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 + 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. |
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| معلومات مُعتمدة: | P51 OD011106 United States OD NIH HHS; R01 AI108415 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: HIV; IL-15 superagonist; N-803; SIV; infection; macaque; vaccine |
| المشرفين على المادة: | 0 (Interleukin-15) EC 3.4.21.- (Granzymes) 0 (Ki-67 Antigen) 0 (Anti-Retroviral Agents) 187348-17-0 (Interleukin-12) 9007-49-2 (DNA) |
| تواريخ الأحداث: | Date Created: 20221003 Date Completed: 20221028 Latest Revision: 20230404 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9599604 |
| DOI: | 10.1128/jvi.01185-22 |
| PMID: | 36190241 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-5514 |
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| DOI: | 10.1128/jvi.01185-22 |