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Human immunodeficiency virus (HIV)-specific natural killer (CD3- cells), CD4, and CD8 T cellular responses were determined in 79 HIV‐1-infected women in response to HIV‐1 peptide pools (Gag, Pol, Nef, Reg, and Env) with use of a whole‐blood intracellular cytokine staining assay that measures interferon-γ and/or interleukin-2. HIV‐specific CD3- cell responses to any region (Env and Reg predominantly targeted) were associated with lower viral load (P = .031) and higher CD4 T cell count (P = .015). Env‐specific CD3- cell responses were stronger in women who had both Gag CD4 and CD8 T cell responses and, in turn, was associated with lower viral load (P = .005). CD3- cell responders had significantly higher representation of CD4 T cell responses to Env and Reg (P = .012 and P = .015, respectively) and higher magnitudes of CD4 T cell responses (P = .017 and P = .037, respectively) than did nonresponders. Peptide‐specific natural killer cells are associated with markers of less severe disease progression among HIV‐1-infected women (lower viral load and higher CD4 T cell count) and with stronger HIV‐specific T cell responses. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) vaccines reduce severe disease and mortality and may lessen transmission, measured by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL). Evaluating vaccine associations in VL at COVID-19 diagnosis in 4 phase 3 randomized, placebo-controlled vaccine trials, July 2020 to July 2021, VL reductions were 2.78 log10 copies/mL (95% confidence interval [CI], 1.38-4.18; n = 60 placebo, 11 vaccine) and 2.12 log10 copies/mL (95% CI, 1.44-2.80; n = 594 placebo, 36 vaccine) for NVX-CoV2373 and mRNA-1273, respectively. Associations were not significant for AZD1222 (0.59 log10 copies/mL; 95% CI, -.19 to 1.36; n = 90 placebo, 78 vaccine) or Ad26.COV2.S (0.23 log10 copies/mL; 95% CI, -.01 to .47; n = 916 placebo, 424 vaccine). Thus, vaccines potentially decreased transmission when ancestral SARS-CoV-2 predominated. Clinical Trials Registration. NCT04470427, NCT04505722, NCT04516746, NCT04611802., Competing Interests: Potential conflicts of interest. A. F. had/has research grants from Pfizer, Merck, Janssen, CyanVac, VaxCo, Moderna, and BioFire Diagnostics; fees for advisory boards from GSK, ADMA Biologics, and Sanofi Pasteur; and fees for data safety monitoring board from Novavax. M. E. S. had/has grants from the National Institutes of Health (NIH) and National Institute of Allergy and Infectious Diseases (NIAID) during the conduct of the study (5UM1AI069470); grants from NIH/NIAID and Gates Foundation outside the submitted work; and grants to her institution from Merck Sharpe and Dohme, Sanofi, and Gilead outside of the submitted work. S. R. W. has received institutional funding from the NIH/NIAID; institutional grants or contracts from Sanofi Pasteur, Janssen Vaccines/Johnson & Johnson, Moderna Tx, Pfizer, Vir Biotechnology, and Worcester HIV Vaccine; has participated on data safety monitoring or advisory boards for Janssen Vaccines/Johnson & Johnson and BioNTech; and his spouse holds stock/stock options in Regeneron Pharmaceuticals. C. M. E. has received research grants from Merck and AstraZeneca; and has participated in Sanofi, Janssen, and Gilead advisory board meetings. N. R. is a paid safety consultant for ICON, CyanVac, and EMMES; served on selected advisory boards for Sanofi, Seqirus, Pfizer, and Moderna; and receives funds to their institution to conduct research from Sanofi, Lilly, Merck, Quidel, Immorna, Vaccine Company, and Pfizer. C. L. G. has received institutional funding from the NIH for the conduct of the Moderna and Novavax studies; and grants to her institution from Gilead and ViiV outside of the submitted work. K. L. K. has received institutional funding from the NIH for the conduct of the Moderna and Novavax studies (UM1 AI 148689); and from Novavax outside of the submitted work. J. A. G. is employed by and holds stock in AstraZeneca. E. A. H. received fees from Oxford University for time spent adjudicating end points for the AstraZeneca/Oxford SARS-CoV-2 vaccine trials conducted in the UK, South Africa, and Brazil. M. D. T. has received institutional funding from the NIH for the conduct of the Moderna and Novavax studies (UM1 AI 148689). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The ALVAC/gp120 + MF59 vaccines in the HIV Vaccine Trials Network (HVTN) 702 efficacy trial did not prevent human immunodeficiency virus-1 (HIV-1) acquisition. Vaccine-matched immunological endpoints that were correlates of HIV-1 acquisition risk in RV144 were measured in HVTN 702 and evaluated as correlates of HIV-1 acquisition., Methods: Among 1893 HVTN 702 female vaccinees, 60 HIV-1-seropositive cases and 60 matched seronegative noncases were sampled. HIV-specific CD4+ T-cell and binding antibody responses were measured 2 weeks after fourth and fifth immunizations. Cox proportional hazards models assessed prespecified responses as predictors of HIV-1 acquisition., Results: The HVTN 702 Env-specific CD4+ T-cell response rate was significantly higher than in RV144 (63% vs 40%, P = .03) with significantly lower IgG binding antibody response rate and magnitude to 1086.C V1V2 (67% vs 100%, P < .001; Pmag < .001). Although no significant univariate associations were observed between any T-cell or binding antibody response and HIV-1 acquisition, significant interactions were observed (multiplicity-adjusted P ≤.03). Among vaccinees with high IgG A244 V1V2 binding antibody responses, vaccine-matched CD4+ T-cell endpoints associated with decreased HIV-1 acquisition (estimated hazard ratios = 0.40-0.49 per 1-SD increase in CD4+ T-cell endpoint)., Conclusions: HVTN 702 and RV144 had distinct immunogenicity profiles. However, both identified significant correlations (univariate or interaction) for IgG V1V2 and polyfunctional CD4+ T cells with HIV-1 acquisition. Clinical Trials Registration . NCT02968849., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: HLA strongly influences human immunodeficiency virus type 1 (HIV-1) disease progression. A major contributory mechanism is via the particular HLA-presented HIV-1 epitopes that are recognized by CD8(+) T-cells. Different populations vary considerably in the HLA alleles expressed. We investigated the HLA-specific impact of the MRKAd5 HIV-1 Gag/Pol/Nef vaccine in a subset of the infected Phambili cohort in whom the disease-susceptible HLA-B*58:02 is highly prevalent., Methods: Viral loads, CD4(+) T-cell counts, and enzyme-linked immunospot assay-determined anti-HIV-1 CD8(+) T-cell responses for a subset of infected antiretroviral-naive Phambili participants, selected according to sample availability, were analyzed., Results: Among those expressing disease-susceptible HLA-B*58:02, vaccinees had a lower chronic viral set point than placebo recipients (median, 7240 vs 122 500 copies/mL; P = .01), a 0.76 log10 lower longitudinal viremia level (P = .01), and slower progression to a CD4(+) T-cell count of <350 cells/mm(3) (P = .02). These differences were accompanied by a higher Gag-specific breadth (4.5 vs 1 responses; P = .04) and magnitude (2300 vs 70 spot-forming cells/10(6) peripheral blood mononuclear cells; P = .06) in vaccinees versus placebo recipients., Conclusions: In addition to the known enhancement of HIV-1 acquisition resulting from the MRKAd5 HIV-1 vaccine, these findings in a nonrandomized subset of enrollees show an HLA-specific vaccine effect on the time to CD4(+) T-cell count decline and viremia level after infection and the potential for vaccines to differentially alter disease outcome according to population HLA composition., Clinical Trials Registration: NCT00413725, DOH-27-0207-1539., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)