Immunostimulatory CpG motifs induce CTL responses to HIV type I oligomeric gp140 envelope protein.
In the present study we investigated the immunomodulatory effects of two adjuvants, liposomal lipid A [L(LA)] and CpG-containing oligodeoxynucleotides (CpG ODN), to the HIV-1 ogp140 envelope protein. Administration of each of these adjuvants separately with unencapsulated ogp140 resulted in low antibody titres. Encapsulation of ogp140 in liposomes containing lipid A resulted in a sixfold increase in anti-ogp140 antibodies. The antibody titres were further enhanced threefold by the addition of CpG ODN. Priming and boosting BALB/c mice with unencapsulated ogp140 with L(LA) or encapsulation in liposomes containing lipid A induced a mixed Th1/Th2 type of immune response. In contrast, immunization with L(ogp140 + LA) plus CpG ODN switched the immune response to a Th-1 response with elevated anti-ogp140 IgG2a antibodies and IFN-gamma levels. Both adjuvants induced excellent ogp140-specific proliferative and CTL responses. Therefore, for the induction of high titre antibodies, but not for cellular responses, the antigen and lipid A have to be present in the same liposomes. These results can have significant implications in directing the Th1 or Th2 differentiation of antigen-specific immune responses in the context of vaccine development.
Rao
Mangala
M
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA. Mangala.Rao@na.amedd.army.mil
Matyas
Gary R
GR
Vancott
Thomas C
TC
Birx
Deborah L
DL
Alving
Carl R
CR
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D018899:CpG Islands / Q000276:immunology*; D019281:Dimerization; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D008050:Lipid A / Q000008:administration & dosage / Q000494:pharmacology; D008081:Liposomes / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects; D054299:env Gene Products, Human Immunodeficiency Virus
D000276:Adjuvants, Immunologic; D015686:Gene Products, env; D008050:Lipid A; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1