Safety and Immunogenicity of Combinations of Recombinant Subtype E and B Human Immunodeficiency Virus Type 1 Envelope Glycoprotein 120 Vaccines in Healthy Thai Adults

Abstract

Safety and immunogenicity of 2 recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein (gp) 120 vaccines derived from SF2 (subtype B) and CM235 (CRF01_AE, Thai E) were evaluated in 370 Thai adults at low risk of HIV infection. Various doses of CM235 (25, 50, or 100 microg) and SF2 (0, 25, or 50 microg) gp120 were used. Eighty volunteers received placebo. There were no serious adverse events related to vaccination. Binding antibody developed in all vaccine recipients. There was no dose response to CM235 gp120, but a dose response to gp120 SF2 was present. Neutralizing antibodies to subtype E HIV-1 NPO3 and subtype B HIV-1 SF2 developed in 84% and 82% of vaccine recipients, respectively. Lymphoproliferative responses were detected in >95% of vaccine recipients. There was no evidence of antigenic interference in HIV-specific humoral or cellular responses. The gp120 Thai E and SF2 vaccines were safe and immunogenic in combination and could be advanced into phase 3 testing.

Reconstruction and Function of Ancestral Center-of-Tree Human Immunodeficiency Virus Type 1 Proteins

“…In this regard, it may be too optimistic to expect that the isolate-based candidate vaccines (currently in phase II and III human clinical trials) could be cross-reactive enough to protect against circulating viruses. Thus, using a central antigen such as COT might contribute to improvements over isolate-based vaccine approaches (26). Although more studies are necessary to determine whether central sequences will elicit cross-reactive responses sufficient to be protective, recent studies with a second-generation CON group M env vaccine showed that it elicited improved levels of neutralizing antibodies in guinea pigs, in some cases stronger and broader than those of contemporary isolates (19).…”

Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies

“…Since neutralizing antibodies against these epitopes do not appear to constitute a significant fraction of the plasma response against Env generated during HIV-1 infection or by vaccination, their epitopes appear to be poorly immunogenic (18). Typically, immune sera from vaccine trials to date at best neutralize only the matched vaccine strain and a few neutralization-sensitive primary isolates (30,32,111,141).…”

Human Immunodeficiency Virus Type 1 Subtype B Ancestral Envelope Protein Is Functional and Elicits Neutralizing Antibodies in Rabbits Similar to Those Elicited by a Circulating Subtype B Envelope

“…First, and the approach followed in current clinical trials, is to choose one or a small number of laboratory-grown or primary viral isolates, typically chosen to approximate a "circulating" strain or to simply match the HIV-1 subtype(s) in the targeted population (16,18,24,52). An advantage of this approach is that it typically employs viral genes derived from a viable virus and thus produces antigens likely to adopt "native" conformations.…”