| AIDS is one of the most severe infectious diseases threatened to human health, it continue to be a growing problem for the world's population, vaccines is the most efficient and economical measure for controlling and preventing infectious diseases, thus the need to develop a safe and efficacious vaccine against HIV is more pressing than ever. DNA vaccine as one of the most potential new vaccine strategies, could not only induce cellular and humoral responses efficiently, but also induce long-time immune memory. However, the modest immunogenicity has been considered as the bottle-neck of DNA vaccine industrialization at all times. The immune strategy of HIV-1 dual expression cassette DNA vaccines pENVPOL and pGAGTNR was optimized in this study, also the prime-boost strategy was used combined with DNA vaccines, recombinand vaccinia VTKgpe and gp140 protein, which significantly enhanced the immune responses elicited by HIV-1 vaccines.Initially, in vivo electroporation(EP) was involved in DNA vaccine delivery to investigated the effect of the immunogenicity of pENVPOL and pGAGTNR. Results showed that in vivo electroporation could significantly enhance the expression of pENVPOL and pGAGTNR in mice. By immunizing with EP,50?g DNA induced 10-fold higher HIV-1 Env specific antibody titer, and 1-fold higher HIV-1 antigens specific cellular responses than which immunized intramuscular(I.M.); also the Env specific antibody titer induced by 5?g DNA with EP was 5-fold higher than 50?g DNA immunized I.M., and equal HIV-1 antigens specific cellular responses induced by these two approaches.Then we evaluated the immune responses induced by DNA vaccines combined with pDRVI4.0 encoded IL-15, BCG and PA-MSHA adjuvants inoculated by I.M. with or without EP. Results showed that HIV-1 DNA vaccines combined with adjuvants inoculated by I.M. with EP induced 4-10-fold higher HIV-1 Env specific humoral responses, and 1-3-fold higher HIV-1 antigens specific cellular responses than which inoculated by I.M. Moreover, inoculating by I.M. with EP, the humoral and cellular responss were significantly enhanced induced by DNA combined adjuvants than DNA.The available immune strategy to enhance the HIV-1 specific immune responses is the prime-boost strategy using DNA, then other vaccines based on live viral vectors or protein. However, the immune interval were not consistent in these prime-boost stragies. In this study we optimized the immune strategy by comparing various immune interval between the DNA, VTKgpe and gpl40. Results showed that DNA vaccine priming thrice followed by VTKgpe 16 weeks later elicited greatest humoral and cellular responses. The gp120 specific binding antibody titer reached 105, and IFN-?+T cells was 5966.4/106 cells. Meanwhile, DNA vaccine priming thrice followed by VTKgpe 16 weeks later, then gp140 protein boost after 4 or 8 weeks induced almost the same immune responses.HIV-1 vaccines and anti-retroviral drugs played a important role in preventing and controlling HIV, however, neither of the strategy showed full protected efficacy from HIV transmistting. At present, within the HIV-1 prevention fields, vaccines and anti-retroviral drugs have been regarded as independent, thus we don't know whether these two prevention method could work better together than individually. In this study, the immune protective efficacy of HIV-1 vaccines combined anti-retroviral drugs in SHIV/Chinese rhesus macaque model was evaluated. Results showed that, after 12 times rectal challenges used SHIV-162P3, the animals of control group were all infected; the ones of vaccine group showed 4/8 protection; the ones of TDF/FTC drug group showed 5/8 protection. What's interesting,7/8 protection was observed in vaccine+drug group, moreover, the peak value of viral load was significantly decreased. Then we figure that HIV-1 vaccines combined with anti-retroviral drugs could provide synergistic protection against acquisition of infection. |
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