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

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


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


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