Optimization Of Multivalent HIV DNA Vaccine Immunization In Mice And Application Of Protein Transduction Domain In HIV Subunit Peptide Vaccine

DNA vaccine and subunit peptide vaccine are two important forms of HIV vaccine. Hereby we explored the optimal immunization in Balb/c mice of multivalent HIV DNA vaccine carrying modified env gene and fused genes of gag, pol and nef of Chinese strain CN54 and the application of protein transduction domain in subunit vaccine.The genetic variation of human immunodeficiency virus type 1 (HIV-1) has created challenges for the development of a preventive AIDS vaccine. Not only would such a vaccine be expected to be safe and immunogenic, but it must also induce immune recognition of a broad spectrum of HIV isolates to prove highly effective. We investigated the cellular immunogenecity of immunizing with several genes of HIV-1 Chinese strain CN54. The genes used as immunogens were: a modified form of envelope, GP140, and a fusion protein of Gag, Pol and Nef, GPNef. The gp140 and gpnef genes are carried by separate plasmids. The env and pol responses were strong in immunized animals and were a little affected by mixture or the spatial separation of gp140 genes from gpnef genes. Cellular immune responses were increased to some extent after spatial separation of gp140 gene from gpnef gene as compared to when the two plasmids were injected as a mixture. Mice immunized three times achived optimal immunal effects. Our results illustrate the importance of being cautious when formulating multivalent genetic vaccines and that it might be possible to overcome lost immune responses through spatial separation of vaccine antigens.Proteins can be efficiently introduced into cells when fused to a protein transduction domain, such as Tat from the human immunodeficiency virus. Antigens fused with PTD were processed by APCs through MHC-I pathway. Here several P24 and Nef antigen of HIV CN54 strain fused with Tat-PTD were purified in prokaryote system as candidate subunit vaccine. However, mice immunized with such recombinant peptides didn't exhibit desirable cellular immune response.