Accelerated clearance of SHIV in rhesus monkeys by virus-like particle vaccines is dependent on induction of neutralizing antibodies

Recombinant, insect cell derived SIV pr56(gag) virus-like particles (VLPs) have been modified either by inserting HIV-I Gp160 derived peptides into th e pr56(gag) precursor or by integrating the complete HIV-I gp120 in the par ticle membrane. To investigate the protective efficacy of these particulate antigens, rhesus macaques were immunized with VLPs both adjuvant-free or a dsorbed to alum. In addition, recombinant Semliki Forest viruses (SFV) expr essing proteins corresponding to the VLP constructs were established and ad ministered as live vaccines in combination with particulate antigens. Vacci nation induced specific humoral responses irrespective of the immunization regimen. However, in contrast to Pr56(gag)-specific antibodies, Env-specifi c antibody titers could not be increased by booster immunizations in this s tudy. Cell-mediated immune responses were detected following vaccination wi th VLP-preparations as well as recombinant SFVs. A tendency towards stimula ting both enhanced cell mediated as well as humoral immune responses was ob served following priming with recombinant SFVs. Upon challenge with SHIV-4 all vaccinated monkeys became infected. However, animals, that were vaccina ted with VLPs presenting the complete gp120, managed to clear virus faster than nonimmunized controls. The observed virus elimination significantly co rrelated with an anamnestic antibody response and an accelerated appearance of neutralizing antibodies postchallenge. (C) 1999 Elsevier Science Ltd. A ll rights reserved.