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 cellular immune responses at the same time. The only response shown to be effective in this regard is virus-neutralization antibodies and virus-specific cytotoxic T-lymphocytes (CTL) directed against the viral antigens. In the present study, it is shown that V3 peptides encapsulated pH-sensitive liposomes elicit the virus neutralization antibodies and virus specific CTL response at the same time in Balb/c mice. None of the immunization protocols elicited an antibody response and CTL response when R15K and T26K was used as immunogen without liposomes. In contrast, antibodies and CTL response were detectable in the mice which were immunized with peptide encapsulated pH-sensitive liposomes. Antibody production was confirmed by virus neutralizing assay. 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 antibody and CTL response was related to the V3 loop peptides size. The T26K (26mer) peptide induced a stronger antibody and CTL response than R15K (15mer) in vivo. Based on the results of this study, T26K was used as a potentially effective HIV-1 vaccine component and T26K encapsulated pH-sensitive liposomes composed of phosphatidylethanolamine-beta-oleoyl-gamma-palmitoyl (POPE)/cholesterol hemisuccinate (CHOH)/monophosphoryl lipid A (MPL) (7:3:0.1, mole ratio) may be used as a potentially immunomodulating adjuvant system for the development of HIV and other viral vaccines.
Chang
J S
JS
Drug Delivery Research Laboratory, Mogam Biotechnology Research Institute, Yongin city, Kyonggi-do, South Korea.
Choi
M J
MJ
Kim
T Y
TY
Cho
S Y
SY
Cheong
H S
HS
D016915:AIDS Vaccines / Q000276:immunology; D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1; D006863:Hydrogen-Ion Concentration; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D008050:Lipid A; D008081:Liposomes; D010446:Peptide Fragments; C048436:monophosphoryl lipid A