The ability of an oligomeric human immunodeficiency virus type 1 (HIV-1) envelope antigen to elicit neutralizing antibodies against primary HIV-1 isolates is improved following partial deletion of the second hypervariable region

Partial deletion of the second hypervariable region from the envelope of th e primary-like SF162 virus increases the exposure of certain neutralization epitopes and renders the virus, SF162 Delta V2, highly susceptible to neut ralization by clade B and non-clade B human immunodeficiency virus (HIV-pos itive) sera (L, Stamatatos and C, Cheng-Mayer, J, Virol, 78:7840-7845, 1998 ), This observation led us to propose that the modified, SF162 Delta V2-der ived envelope may elicit higher titers of cross-reactive neutralizing antib odies than the unmodified SF162-derived envelope. To test this hypothesis, we immunized rabbits and rhesus macaques with the gp140 form of these two e nvelopes, In rabbits, both immunogens elicited similar titers of binding an tibodies but the modified immunogen was more effective in eliciting neutral izing antibodies, not only against the SF162 Delta V2 and SF162 viruses but also against several heterologous primary HIV type 1 (HIV-1) isolates. In rhesus macaques both immunogens elicited potent binding antibodies, but aga in the modified immunogen was more effective in eliciting the generation of neutralizing antibodies against the SF162 Delta V2 and SF162 viruses, Anti bodies capable of neutralizing several, but not all, heterologous primary H IV-1 isolates tested were elicited only in macaques immunized with the modi fied immunogen, The efficiency of neutralization of these heterologous isol ates was lower than that recorded against the SF162 isolate, Our results st rongly suggest that although soluble oligomeric envelope subunit vaccines m ay elicit neutralizing antibody responses against heterologous primary HIV- 1 isolates, these responses will not be broad and potent unless specific mo difications are introduced to increase the exposure of conserved neutraliza tion epitopes.