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176   The HIV Antigen-Specific Cellular and Humoral Immune Responses in Mice Induced by DNA Prime-Recombinant Vaccinia or VLPs Boost Regime  

L. Chen1, X. Zhang1, J. Zhang1, Y. Xiao1, X. Tao1, L. Wu1, K. Hong1, R. Wagner2, H. Wolf2, and Y. Shao*1
1Natl. Ctr. for AIDS Prevention and Control, Chinese Academy for Preventive Med., China and 2Inst. of Med. Microbiology, Univ. of Regensburg, Germany


Background: The B/C recombinant strain was proved to be one of the most prevalent HIV strains circulating in China. HIV vaccines based on this strain are being studied in National Center for AIDS Prevention and Control (NARL). To determine an optimized immune regimen, the immune responses induced by combinations of different vaccines were evaluated in this study.
Methods: Three kinds of candidate HIV vaccines expressing HIV-1 gag and gp120 genes of the B/C recombinant HIV strain in China were constructed. They are codon usage optimized DNA vaccine, recombinant vaccinia virus (derived from Chinese Tiantan vaccinia strain), and virus-like particles expressed by baculovirus expression system. The synthetic DNA plasmids were intramuscularly inoculated into female Balb/c mice 3 times with a 4-week interval. Two weeks after the last immunization, the mice were boosted with either VLPs or recombinant vaccinia virus via subcutaneous injection. The antigen-specific antibodies, CTL (with 51Cr release assay stimulated with P24-derived 9-mer, V3-derived 15-mer peptides), neutralizing antibody, and the cytokine secretion were evaluated.
Results: Better overall immune responses were observed with vectors expressing gp120 compared with those expressing gag. Various combinations of candidate vaccines were tested in different prime-boost regimens. Although the highest antibody titers were found in DNA prime-VLPs boost group, the higher neutralizing antibody still comes from the DNA prime-vaccinia boost group. The stronger CTL responses were observed in the groups primed with DNA plasmids followed by boosting with either DNA or recombinant vaccinia compared with the DNA prime-VLPs boost group. The DNA prime-DNA or recombinant vaccinia boost mice demonstrated higher ratios of IgG2a/IgG1 and IFNgamma/IL-5, indicated by a Th1 immune response. Recombinant vaccinia-boosted mice induced stronger CTL response than mice boosted with DNA plasmid.
Conclusions: The strongest neutralizing antibody and CTL immune response was induced by DNA prime-recombinant vaccinia virus boost regime, suggesting this is an alternative strategy for further HIV vaccine study on monkey and in clinical trials.


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