1. Polytopic fractional delivery of an HIV vaccine alters cellular responses and results in increased epitope breadth in a phase 1 randomized trial
- Author
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Miner, Maurine D, deCamp, Allan, Grunenberg, Nicole, De Rosa, Stephen C, Fiore-Gartland, Andrew, Bar, Katherine, Spearman, Paul, Allen, Mary, Yu, Pei-Chun, Manso, Bryce, Frahm, Nicole, Kalams, Spyros, Baden, Lindsey, Keefer, Michael C, Scott, Hyman M, Novak, Richard, Van Tieu, Hong, Tomaras, Georgia D, Kublin, James G, McElrath, M Juliana, Corey, Lawrence, Frank, Ian, Team, HVTN 085 Study, Kalichman, Artur, Edlefsen, Paul, Enama, Mary, Hural, John, Holt, Renee, Dunbar, Debora, Crawford, Dave, Maki, Ian, Johannessen, Jan, Estep, Scharla, Grigoriev, Yevgeny, Madenwald, Tamra, Hansen, Marianne, Holman, Drienna, Fair, Ramey, Meyer, Genevieve, and Luke-Kilolam, Anya
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Sexually Transmitted Infections ,Biotechnology ,Infectious Diseases ,Clinical Research ,Prevention ,Vaccine Related ,Clinical Trials and Supportive Activities ,Immunization ,HIV/AIDS ,Vaccine Related (AIDS) ,3.4 Vaccines ,Infection ,Good Health and Well Being ,Humans ,AIDS Vaccines ,Epitopes ,HIV Infections ,CD4-Positive T-Lymphocytes ,Vaccination ,Immunoglobulin G ,HIV ,Fractionated delivery ,Polytopic vaccination ,Ad5 ,Epitope breadth ,HVTN 085 Study Team ,Clinical Sciences ,Public Health and Health Services ,Clinical sciences ,Epidemiology - Abstract
BackgroundElicitation of broad immune responses is understood to be required for an efficacious preventative HIV vaccine. This Phase 1 randomized controlled trial evaluated whether administration of vaccine antigens separated at multiple injection sites vs combined, fractional delivery at multiple sites affected T-cell breadth compared to standard, single site vaccination.MethodsWe randomized 90 participants to receive recombinant adenovirus 5 (rAd5) vector with HIV inserts gag, pol and env via three different strategies. The Standard group received vaccine at a single anatomic site (n = 30) compared to two polytopic (multisite) vaccination groups: Separated (n = 30), where antigens were separately administered to four anatomical sites, and Fractioned (n = 30), where fractions of each vaccine component were combined and administered at four sites. All groups received the same total dose of vaccine.FindingsCD8 T-cell response rates and magnitudes were significantly higher in the Fractioned group than Standard for several antigen pools tested. CD4 T-cell response magnitudes to Pol were higher in the Separated than Standard group. T-cell epitope mapping demonstrated greatest breadth in the Fractioned group (median 8.0 vs 2.5 for Standard, Wilcoxon p = 0.03; not significant after multiplicity adjustment for co-primary endpoints). IgG binding antibody response rates to Env were higher in the Standard and Fractioned groups vs Separated group.InterpretationThis study shows that the number of anatomic sites for which a vaccine is delivered and distribution of its antigenic components influences immune responses in humans.FundingNational Institute of Allergy and Infectious Diseases, NIH.
- Published
- 2024