SAFETY AND IMMUNOGENICITY OF AN HLA-BASED HIV ENVELOPE POLYVALENT SYNTHETIC PEPTIDE IMMUNOGEN

Objective: To evaluate the safety and immunogenicity of a polyvalent ( PV) HIV envelope synthetic peptide immunogen, C4-V3. The immunogen com prised four peptides containing T-helper epitopes from the fourth cons tant region (C4) of gp120 of HIV-1(MN), and T-helper, cytotoxic T-lymp hocyte HLA-B7-restricted, and B-cell neutralizing epitopes from the gp 120 third variable region (V3) of four clade B HIV-1 isolates, HIV-1(M N), HIV-1(RF), HIV-1(EV91), and HIV-1(CanOA). Design: A pilot, Phase I controlled trial [Division of AIDS Treatment Research Initiative (DAT RI) 010] conducted at a single center. Methods: Ten HIV-infected, HLA- B7-positive patients with CD4 cells > 500 x 10(6)/l were enrolled. Eig ht patients received the C4-V3 PV immunogen emulsified in incomplete F reund's adjuvant in five intramuscular injections over 24 weeks, and t wo controls received incomplete Freund's adjuvant alone. All subjects were followed for 52 weeks. Results: Four out of eight C4-V3 PV recipi ents generated at least fourfold rise in serum antibody titers to at l east three immunogen peptides in contrast to none of the control subje cts. Four out of eight C4-V3 PV recipients and none of the controls ha d an at least fourfold rise in neutralizing antibodies to either HIV-1 (MN), HIV-1(RF), or HIV-1(4489-5) laboratory-adapted HIV isolates. H-3 -Thymidine incorporation assays of peripheral blood mononuclear cells increased at least fivefold over the baseline stimulation index to at least one of the immunogen peptides in two consecutive post-immunizati on timepoints in five out of eight C4-V3 PV recipients versus none of the controls. CD4 cell counts and plasma HIV RNA levels did not change in patients who received either C4-V3 PV or adjuvant alone. Adverse e vents consisted primarily of grade 1 injection site reactions in six s ubjects (four C4-V3 recipients, two controls). Conclusions: C4-V3 PV s ynthetic peptides demonstrated both immunogenicity and safety in HIV-i niected patients. (C) 1998 Lippincott-Raven Publishers.