Affordable Access

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

Authors
  • 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
  • And 20 more
Publication Date
Feb 01, 2024
Source
eScholarship - University of California
Keywords
License
Unknown
External links

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.

Report this publication

Statistics

Seen <100 times