Polytopic fractional delivery of an HIV vaccine alters cellular responses and results in increased epitope breadth in a phase 1 randomized trial.

Autor:	Miner MD; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA. Electronic address: mminer@fredhutch.org., deCamp A; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA., Grunenberg N; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA., De Rosa SC; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA., Fiore-Gartland A; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA., Bar K; University of Pennsylvania, Philadelphia, PA, USA., Spearman P; Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Allen M; Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Yu PC; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA., Manso B; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA., Frahm N; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA., Kalams S; Vanderbilt University Medical Center, Nashville, TN, USA., Baden L; Brigham and Women's Hospital, Boston, MA, USA., Keefer MC; Department of Medicine, University of Rochester School of Medicine & Dentistry, Rochester, NY, USA., Scott HM; San Francisco Department of Public Health, San Francisco, CA, USA., Novak R; University of Illinois, Chicago, IL, USA., Van Tieu H; Laboratory of Infectious Disease Prevention, Lindsley F. Kimball Research Institute, New York Blood Center, New York City, NY, USA; Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York City, NY, USA., Tomaras GD; Department of Surgery, Duke University, Durham, NC, USA., Kublin JG; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA., McElrath MJ; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA., Corey L; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA., Frank I; University of Pennsylvania, Philadelphia, PA, USA.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2024 Feb; Vol. 100, pp. 104987. Date of Electronic Publication: 2024 Feb 01.
DOI:	10.1016/j.ebiom.2024.104987
Abstrakt:	Background: Elicitation 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. Methods: We 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. Findings: CD8 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. Interpretation: This 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. Funding: National Institute of Allergy and Infectious Diseases, NIH. Competing Interests: Declaration of interests MAA is employed by NIAID, the funder of the study. HVT, KJB, SAK, AFG, LC, GDT, NF, NG, SCDR reports receiving institutional grants from the NIH. IF reports institutional grants and participation on Boards of Gilead and Viiv; LB reports institutional grants and participation on Boards of the FDA and NIAID; MJM reports institutional grants, participation on Boards of Ragon Institute, Keystone Symposia and NIH VRC, and a patent on HIV immunogens. The rest of the authors as well as HVTN 085 Study Team declare no conflicts of interest. (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu