Safety and Immunogenicity of a Randomized Phase 1 Prime-Boost Trial With ALVAC-HIV (vCP205) and Oligomeric Glycoprotein 160 From HIV-1 Strains MN and LAI-2 Adjuvanted in Alum or Polyphosphazene. (11th February 2016)

• Record Type: Journal Article
• Authors: O'Connell, Robert J.; Excler, Jean-Louis; Polonis, Victoria R.; Ratto-Kim, Silvia; Cox, Josephine; Jagodzinski, Linda L.; Liu, Michelle; Wieczorek, Lindsay; McNeil, John G.; El-Habib, Raphaelle; Michael, Nelson L.; Gilliam, Bruce L.; Paris, Robert; VanCott, Thomas C.; Tomaras, Georgia D.; Birx, Deborah L.; Robb, Merlin L.; Kim, Jerome H.
• Is Part Of: Journal of infectious diseases. Volume 213:Number 12(2016:Jun. 15)
• Page Start: 1946
• Page End: 1954
• Publication Date: 2016-02-11
• Subjects: HIV -- vaccine -- prime-boost -- neutralizing antibody -- adjuvant -- polyphosphazene; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiw059
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background. Prime-boost regimens comprising ALVAC-HIV (prime) and human immunodeficiency virus type 1 (HIV) Env (boost) induce HIV-specific neutralizing antibody and cell-mediated immune responses, but the impact of boost schedule and adjuvant requires further definition. Methods. A phase 1 trial was conducted. In part A (open label), 19 volunteers received oligomeric glycoprotein 160 from HIV strains MN and LAI-2 (ogp160 MN/LAI-2) with dose escalation (25, 50, 100 μg) and either polyphosphazene (pP) or alum adjuvant. In part B, 72 volunteers received either placebo (n=12) or recombinant canarypox virus expressing HIV antigens (ALVAC-HIV [vCP205]) with different doses and schedules of ogp160 MN/LAI-2 in pP or alum (n = 60). Results. The vaccines were safe and well tolerated, with no vaccine-related serious adverse events. Anti–gp70 V1V2 antibody responses were detected in 17 of 19 part A volunteers (89%) and 10%–100% of part B volunteers. Use of a peripheral blood mononuclear cell–based assay revealed that US-1 primary isolate neutralization was induced in 2 of 19 recipients of ogp160 protein alone (10.5%) and 5 of 49 prime-boost volunteers (10.2%). Among ogp160 recipients, those who received pP were more likely than those who received alum to have serum that neutralized tier 2 viruses (12% vs 0%; P = .015). Conclusions. Administration of ogp160 with pP induces primary isolate tier 2 neutralizing antibody responses in a small percentage of volunteers, demonstrating proof of concept and underscoring the importance of further optimization of prime-boost strategies for HIV infection prevention. Clinical Trials Registration. NCT00004579.