Immunogenicity of synthetic HIV-1 V3 loop peptides by MPL adjuvanted pH-sensitive liposomes

A successful HIV-1 vaccine should be capable of generating humoral and cell ular immune responses at the same rime. The only response shown to be effec tive in this regard is virus-neutralization antibodies and virus-specific c ytotoxic T-lymphocytes (CTL) directed against the viral antigens. In the pr esent study, it is shown that V3 peptides encapsulated pH-sensitive liposom es elicit the virus neutralization antibodies and virus specific CTL respon se at the same time in Balb/c mice. None of the immunization protocols elic ited an antibody response and CTL response when R15K and T26K was used as i mmunogen without liposomes. In contrast, antibodies and CTL response were d etectable in the mice which were immunized with peptide encapsulated pH-sen sitive liposomes. Antibody production was confirmed by virus neutralizing a ssay. CD4+ T-cells are involved in target cell lysis to some degree but CTL activity is mainly due to the CD8+ T-cells. The consistency of the antibod y and CTL response was related to the V3 loop peptides size. The T26K (26me r) peptide induced a stronger antibody and CTL response than R15K (15mer) i n vivo. Based on the results of this study, T26K was used as a potentially effective HIV-1 vaccine component and T26K encapsulated pi-I-sensitive lipo somes composed of phosphatidylethanolaminl-beta-oleoyl-gamma-palmitoyl (POP E)/cholesterol hemisuccinate (CHOH)/monophosphoryl lipid A (MPL) (7:3:0.1, mole ratio) may be used as a potentially immunomodulating adjuvant system f or the development of HIV and other viral vaccines. (C) 1999 Elsevier Scien ce Ltd. All rights reserved.