The induction of a potent and long-lasting,
broadly neutralizing antibody response is one of the most promising approaches in HIV-1 vaccination. Recently, we demonstrated that Gag-specific T helper cells induced by
DNA priming can enhance and modulate the HIV Env-specific B cell response upon virus-like particle (VLP) boost by intrastructural help (ISH). In order to minimize the induction of potentially harmful HIV specific TH cells, we explored the possibility to harness the heterologous TH cells induced by a recombinant
tuberculosis subunit vaccine H1, which contains a fusion
protein of Ag85B and ESAT-6
antigens in combination with the liposomal adjuvant CAF01. To provide ISH, immunodominant MHC-II restricted
peptides from the H1
vaccine were genetically incorporated into the HIV 1
Gag protein and used for HIV VLP production. ISH effects on Env-specific antibody levels and B cell differentiation were analyzed in mice primed against H1 and boosted with VLPs. In contrast to non-primed mice, a significant increase of Env-specific
IgG levels for up to 26 weeks after the last immunization was observed. This increase was largely caused by elevated
IgG2b and IgG2c levels in mice that received H1 priming. Additionally, ISH enhanced the frequency of Env-specific long-lived plasma cells in the bone marrow. In this study, we were able to demonstrate that a heterologous prime-boost regimen consisting of the H1
tuberculosis subunit vaccine and T helper
epitope modified HIV-1 VLPs resulted in enhanced HIV Env antibody and B cell responses, mediated by intrastructural help.