Cytotoxic T Cells and Neutralizing Antibodies Induced in Rhesus Monkeys by Virus-like Particle HIV Vaccines in the Absence of Protection from SHIV Infection

Abstract

HIV Pr55gaghas in the absence of other viral components the capacity to self assemble in budding noninfectious virus-like particles (VLP). The immunological spectrum of the HIV-1IIIBgag-derived VLP was expanded either by stable anchoring of chimeric modified gp120 on the surface of the VLP (type 1) or by replacing sequences of the Pr55gagprecursor by the V3 loop and a linear portion of the CD4 binding domain (type 2). This noninfectious antigen delivery system was evaluated for immunogenicity and efficacy in rhesus macaques without adjuvants. Intramuscular immunization with both types of VLP induced high titers ofgag-specific antibodies ranging from 1/8000 to 1/510,000 for type 1 VLP and from 1/4000 to 1/16,000 for type 2 VLP. Only animals immunized with type 1 VLP developed substantial endpoint titers ofenv-specific antibodies (1/2000–1/32,000) with a neutralizing capacity at serum dilutions of 1/32–1/128.Gag- andenv-specific cytotoxic T lymphocyte (CTL) activity was induced by both types of VLP at similar levels. Four weeks after the last immunization animals were challenged intravenously with 20 MID50of the cell free homologous envelope simian/HIV-1IIIBchimeric challenge stock. Despite HIV-1-specific neutralizing and CTL responses, all vaccinated animals became infected.