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

• Published in: PLoS pathogens 2019-12, Vol.15 (12), p.e1008121-e1008121
• Main Authors: Schifanella, Luca, Barnett, Susan W, Bissa, Massimiliano, Galli, Veronica, Doster, Melvin N, Vaccari, Monica, Tomaras, Georgia D, Shen, Xiaoying, Phogat, Sanjay, Pal, Ranajit, Montefiori, David C, LaBranche, Celia C, Rao, Mangala, Trinh, Hung V, Washington-Parks, Robyn, Liyanage, Namal P M, Gorini, Giacomo, Brown, Dallas R, Liang, Frank, Loré, Karin, Venzon, David J, Magnanelli, William, Metrinko, Michelle, Kramer, Josh, Breed, Matthew, Alter, Galit, Ruprecht, Ruth M, Franchini, Genoveffa
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; AIDS Vaccines - chemistry; AIDS Vaccines - immunology; Alum Compounds - pharmacology; Aluminum; Aluminum hydroxide; Animal sciences; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Armed forces; Biology and life sciences; Biomedical research; C-reactive protein; Cancer; CXCL10 protein; Dosage; Female; Glycoprotein gp120; HIV; HIV Infections; Human immunodeficiency virus; IL-1β; Immunoglobulin A; Immunoglobulin G; Immunoglobulins; Immunology; Inflammation; Laboratory animals; Macaca mulatta; Medical research; Medicin och hälsovetenskap; Medicine and Health Sciences; Mucosa; Neutralization; People and Places; Proteins; Research and Analysis Methods; Risk; Risk reduction; SAIDS Vaccines - chemistry; SAIDS Vaccines - immunology; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Studies; Supervision; Vaccine efficacy; Vaccines; Viral Vaccines - chemistry; Viral Vaccines - immunology; Viruses
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1008121

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.