Broad HIV-1 neutralizing antibody response induced by heterologous gp140/gp145 DNA prime-vaccinia boost immunization

Objective: To develop an effective HIV vaccine strategy that can induce cross-reactive neutralizing antibody. Methods: Codon-optimized gp140 and gp145 env genes derived from HIV-1(cn54), a CRF07 B'/C recombinant strain, were constructed as DNA and recombinant Tiantan vaccinia (rTV) vaccines. The effect of heterologous immunization with gp140 and gp145 was tested in mice and guinea pigs. T cell responses were detected using the IFN-gamma ELISPOT assay. A panel of primary isolates of clade B' and B'/C HIV-1 and TZM-bl cells was used to determine the neutralizing activity of immunized sera. Results: The neutralizing antibodies (NAbs) induced by the heterologous immunogen immunization neutralized all HIV-1 B' and B'/C primary isolates in the guinea pig model. Gp145 and gp140 heterologous prime-boost induced the best neutralizing antibody response with a broad neutralizing spectrum and the highest titer of 1:270 at 6 weeks after the last inoculation. However, the T cell response to HIV-1 peptides was significantly weaker than the gp145+gp145 homologous prime-boost. Conclusions: This heterologous prime-boost immunization strategy could be used to design immunogengenerating broad neutralizing antibodies against genetic variance pathogens. (C) 2012 Elsevier Ltd. All rights reserved.