Parenteral delivery of the vaccine candidate TERAVAC-HIV-1 bypasses pre-existing immune response to the hepatitis B virus antigens in mice

The recombinant hepatitis B virus surface (HBsAg) and core (HBcAg) virus like particles (VLPs) have the ability to serve as carriers of foreign B cell and CTL epitopes. Different approaches have been used to couple the target epitopes, like the insertion into the primary sequence of the VLP, covalent and noncovalent linkage. Particularly, the non-covalent linkage was used to develop the vaccine formulation Teravac against the human immunodeficiency virus type 1 (HIV-1). Teravac is an aggregate of the recombinant protein CR3 of HIV-1 and both HBV VLPs. Previous studies have shown that immunization of Teravac in mice induced a Th1 response with CD8+ T cells. However, because millions of people are infected with the HBV and millions of doses of the HBV vaccine have been administered worldwide, the pre-existing immune response to the HBcAg and/or HBsAg is a rather frequent event. This opens de question about the impact of the anti-HBc and/or anti-HBs antibody response on the CR3(HIV)-specific cellular response elicited with Teravac. To answer this question, the effect of the pre-existing anti-HBc and the combined anti-HBc/anti-HBs antibodies was studied in mice. Our findings suggest that the induction of CR3(HIV)-specific cellular responses of CD4+ and CD8+ cells are not impaired by pre-existing high IgG titers in either situation.