Prime-boost vaccination with HIV-1 Gag protein and cytosine phosphate guanosine oligodeoxynucleotide, followed by adenovirus, induces sustained and robust humoral and cellular immune responses.
A prophylactic vaccine for HIV-1 will probably require the induction and maintenance of both humoral and cellular immunity. One current strategy to achieve such long term immune responses is a prime-boost vaccination approach using a DNA priming inoculation, followed by recombinant viral boost. In this report we use a novel prime-boost approach in which the priming injections consist of recombinant HIV-1 Gag protein mixed with cytosine phosphate guanosine oligodeoxynucleotide (CpG ODN), followed by recombinant adenoviral boost expressing HIV-1 Gag. Analysis of the immune responses indicates that HIV-1 Gag protein plus CpG ODN immunization alone induces potent humoral as well as Th1 and CD8+ T cell responses. Boosting with recombinant adenovirus strikingly enhances CD8+, but not Th1, T cell responses, resulting in CD8+ T cell responses far greater in magnitude than Th1 responses. Furthermore, the Th1 and CD8+ T cell responses following prime-boost immunization were seen in both lymphoid and peripheral mucosal organs and were sustained over several months. Together, these data suggest a new immunization approach for elicitation of long term humoral and cellular immune responses.
Tritel
Marc
M
Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, USA.
Stoddard
Amy M
AM
Flynn
Barbara J
BJ
Darrah
Patricia A
PA
Wu
Chang-you
CY
Wille
Ulrike
U
Shah
Javeed A
JA
Huang
Yue
Y
Xu
Ling
L
Betts
Michael R
MR
Nabel
Gary J
GJ
Seder
Robert A
RA
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D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015483:HIV Antibodies; D009838:Oligodeoxyribonucleotides; D014614:Vaccines, Synthetic