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

Authors :
Schifanella L
Barnett SW
Bissa M
Galli V
Doster MN
Vaccari M
Tomaras GD
Shen X
Phogat S
Pal R
Montefiori DC
LaBranche CC
Rao M
Trinh HV
Washington-Parks R
Liyanage NPM
Gorini G
Brown DR
Liang F
Loré K
Venzon DJ
Magnanelli W
Metrinko M
Kramer J
Breed M
Alter G
Ruprecht RM
Franchini G
Source :
PLoS pathogens [PLoS Pathog] 2019 Dec 03; Vol. 15 (12), pp. e1008121. Date of Electronic Publication: 2019 Dec 03 (Print Publication: 2019).
Publication Year :
2019

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.<br />Competing Interests: The authors have declared that no competing interests exist.

Details

Language :
English
ISSN :
1553-7374
Volume :
15
Issue :
12
Database :
MEDLINE
Journal :
PLoS pathogens
Publication Type :
Academic Journal
Accession number :
31794588
Full Text :
https://doi.org/10.1371/journal.ppat.1008121