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

Robert J. O'Connell*, Jean Louis Excler, Victoria R. Polonis, Silvia Ratto-Kim, Josephine Cox, Linda L. Jagodzinski, Michelle Liu, Lindsay Wieczorek, John G. McNeil, Raphaelle El-Habib, Nelson L. Michael, Bruce L. Gilliam, Robert Paris, Thomas C. Vancott, Georgia D. Tomaras, Deborah L. Birx, Merlin L. Robb, Jerome H. Kim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish
Pages (from-to)1946-1954
Number of pages9
JournalJournal of Infectious Diseases
Volume213
Issue number12
DOIs
StatePublished - 15 Jun 2016
Externally publishedYes

Keywords

  • Adjuvant
  • HIV
  • Neutralizing antibody
  • Polyphosphazene
  • Prime-boost
  • Vaccine

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this