Immunostimulatory CpG motifs induce CTL responses to HIV type I oligomeric gp140 envelope protein |
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Authors: | Rao Mangala Matyas Gary R Vancott Thomas C Birx Deborah L Alving Carl R |
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Institution: | Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA. Mangala.Rao@na.amedd.army.mil |
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Abstract: | 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. |
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