Immunogenicity comparison between codon optimized HIV-1 CRF BC_07 gp140 and gp145 vaccines

To develop an effective vaccine against the most prevalent HIV strain "B'/C recombinant" in China, we compared the immunogenicity of B'/C-derived gp140 and gp145. The codon optimized gp140 and gp145 env gene derived from CN54, an ancestor-like B'/C recombinant strain, were synthesized and cloned into a plasmid as DNA vaccines, designated as pDRVISV140 and pDRVISV145, respectively. BALB/c mice were inoculated three times at week 0, 2, and 4 and sacrificed at week 7. Both T cell immunity and humoral immunity were determined. The mock vector pDRVISV1.0 carrying no HIV immunogen was included as control. Our data showed that B'/C recombinant-derived gp145 mounted stronger T cell and broader linear antibody but less binding antibody immune responses than gp140 did. Though both gp145 and gp140 raised neutralization antibodies against laboratory-adapted strain SF33, both failed to neutralize B' or B'/C clade primary strains. Overall, this is the first time the immunogenicity of B'/C recombinant-derived gp140 and gp145 was examined and compared; our data prefer B'/C-derived gp145 to gp140 as an HIV vaccine immunogen. The failure to induce neutralization antibodies against primary isolates indicates that it is insufficient to enhance the immunogenicity of conserved epitopes by simply employing gp145 or gp140; strategies to enhance antibody responses against conserved epitopes should be explored further.