Sequential priming and boosting with heterologous HIV immunogens predominantly stimulated T cell immunity against conserved epitopes

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Abstract
Background: The effort to develop an effective preventive vaccine against HIV-1 infection is challenged by the wide genetic diversity of HIV-1 among different isolates. Objectives: To explore a new vaccination strategy by using heterologous HIV immunogens derived from different clades for sequential priming and boosting. Methods: HIV Env and Gag immunogens derived from Thailand B (B′), C/B′ recombinant and A/E recombinant were selected as these three clades account for 29%, 45% and 15% of HIV-1 prevalence in China, respectively. Three humanized fusion genes of env and gag derived from those three clades were synthesized and inserted into DNA and recombinant Tiantan vaccinia vectors as model vaccines. C57BL/6 and Balb/c mice were used as animal model. Peptides spanning the entire Env and Gag were used as stimuli and Elispot assay was used to assess the T cell immunity. Results: Sequential priming and boosting was observed with heterologous HIV immunogens predominantly stimulated T cell immunity against conserved epitopes, whereas a single vaccine derived from one clade or the mixture of multiple vaccines from different clades primarily raised T cells against less conservative or non-conservative epitopes. Conclusions: This is the first demonstration of a practical strategy to raise immune responses against conserved epitopes. This strategy has important implications for vaccine development against HIV and other pathogens that have high genetic diversity, such as influenza.

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