ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type

Luca Schifanella, Susan W Barnett, Massimiliano Bissa, Veronica Galli, Melvin N Doster, Monica Vaccari, Georgia D Tomaras, Xiaoying Shen, Sanjay Phogat, Ranajit Pal, David C Montefiori, Celia C LaBranche, Mangala Rao, Hung V Trinh, Robyn Washington-Parks, Namal P M Liyanage, Giacomo Gorini, Dallas R Brown, Frank Liang, Karin LoréDavid J Venzon, William Magnanelli, Michelle Metrinko, Josh Kramer, Matthew Breed, Galit Alter, Ruth M Ruprecht, Genoveffa Franchini

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The ALVAC-HIV clade B/AE and equivalent SIV-based/gp120 + Alum vaccines successfully decreased the risk of virus acquisition in humans and macaques. Here, we tested the efficacy of HIV clade B/C ALVAC/gp120 vaccine candidates + MF59 or different doses of Aluminum hydroxide (Alum) against SHIV-Cs of varying neutralization sensitivity in macaques. Low doses of Alum induced higher mucosal V2-specific IgA that increased the risk of Tier 2 SHIV-C acquisition. High Alum dosage, in contrast, elicited serum IgG to V2 that correlated with a decreased risk of Tier 1 SHIV-C acquisition. MF59 induced negligible mucosal antibodies to V2 and an inflammatory profile with blood C-reactive Protein (CRP) levels correlating with neutralizing antibody titers. MF59 decreased the risk of Tier 1 SHIV-C acquisition. The relationship between vaccine efficacy and the neutralization profile of the challenge virus appear to be linked to the different immunological spaces created by MF59 and Alum via CXCL10 and IL-1β, respectively.

Original languageEnglish (US)
Pages (from-to)e1008121
JournalPLoS pathogens
Volume15
Issue number12
DOIs
StatePublished - Dec 2019
Externally publishedYes

Keywords

  • AIDS Vaccines/chemistry
  • Adjuvants, Immunologic/pharmacology
  • Alum Compounds/pharmacology
  • Animals
  • Antibodies, Neutralizing/immunology
  • Antibodies, Viral/immunology
  • Female
  • HIV Infections
  • Macaca mulatta
  • SAIDS Vaccines/chemistry
  • Simian Acquired Immunodeficiency Syndrome
  • Simian Immunodeficiency Virus
  • Viral Vaccines/chemistry

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

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