Eliciting broad neutralizing antibody to HIV-1: envelopes of different lentivirus cross immunization by prime-boost vaccination

Abstract

The greatest challenge of HIV vaccine development lies in the diversity of circulating HIV-1 strains. For an effective vaccine, neutralizing antibodies are assumed to be of crucial importance, but previous attempts results only very limited breadth and potency of Nab titer. While the amino acid sequences of lentivirus envelope have many differences, those envelope proteins share almost same structural conformations. If the envelopes of different lentivirus were used immune animals, the response to the conserved sites will be strengthened while the un-conserved sites will not be. In this study, compared to only protein immunization regimen, HIV-1 CN54 gp140 DNA prime and protein boost strategy generated Nab titer increased significantly. So, the prime-boost strategy and HIV-1 CN54 gp140 protein were employed to different lentivirus cross immunization schedule. The results indicated that, the different lentivirus and HIV-1 cross immune by prime-boost strategy elicited breath and potency neutralization antibody to tier 1, tier 2, and tier 3 viruses with 14 tested viruses. To tested tier 2 and tier 3 viruses, in SIV and HIV-1 cross immunization group, the neutralization breadth of ID50 is 91.7% and the breadth of ID70 is 50%; in HIV-1, FIV and SIV cross immunization group, the breadth of ID50 is 83.3% and the breadth of ID70 is 58.3%, while in only HIV-1 vaccinated group, the breadth of ID50 is 75% and the breadth of ID70 is only 25%. These data demonstrate that HIV-1 and different lentivirus especially with SIV cross immunization by prime-boost strategy elicit broad neutralizing antibodies much better than only HIV-1 immunization.