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

English version

Autoři: Luca Schifanella ^aff001; Susan W. Barnett ^aff002; Massimiliano Bissa ^aff001; Veronica Galli ^aff001; Melvin N. Doster ^aff001; Monica Vaccari ^aff001; Georgia D. Tomaras ^aff003; Xiaoying Shen ^aff003; Sanjay Phogat ^aff004; Ranajit Pal ^aff005; David C. Montefiori ^aff003; Celia C. LaBranche ^aff003; Mangala Rao ^aff006; Hung V. Trinh ^aff006; Robyn Washington-Parks ^aff001; Namal P. M. Liyanage ^aff001; Dallas R. Brown ^aff001; Frank Liang ^aff008; Karin Loré ^aff008; David J. Venzon ^aff009; William Magnanelli ^aff010; Michelle Metrinko ^aff010; Josh Kramer ^aff010; Matthew Breed ^aff010; Galit Alter ^aff011; Ruth M. Ruprecht ^aff012; Genoveffa Franchini ^aff001
Působiště autorů: Animal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America ^aff001; Novartis Vaccines and Diagnostics, Inc, Cambridge, Massachusetts, United States of America ^aff002; Duke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America ^aff003; Sanofi Pasteur, Swiftwater, Pennsylvania, United States of America ^aff004; Advanced BioScience Laboratories, Inc., Rockville, Maryland, United States of America ^aff005; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America ^aff006; U.S. Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America ^aff007; Karolinska Institute, Stockholm, Sweden ^aff008; Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America ^aff009; Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, Maryland, United States of America ^aff010; Ragon Institute of MGH, MIT, and Harvard Cambridge, Boston, Massachusetts, United States of America ^aff011; Texas Biomedical Research Institute, San Antonio, Texas, United States of America ^aff012
Vyšlo v časopise: ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008121
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008121

Souhrn

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.

Klíčová slova:

Antibodies – Blood plasma – Immunologic adjuvants – Macaque – Rhesus monkeys – Vaccines – Alumni

Zdroje

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