Lactococcus lactis expressing HIV antigens on a Group A Streptococcus (GAS) pilus serves as potential dual mucosal vaccine against HIV and GAS

Abstract

Abstract Due to the majority of HIV/SIV transmissions occurring via the mucosal route, a mucosal vaccine that generates immune responses along the genitorectal tract may provide the tools needed to combat HIV/SIV in its earliest stages of infection. We recently demonstrated that an orally delivered mucosal vaccine based around the probiotic bacterium Lactococcus lactis expressing HIV/SIV antigens fused to a cell wall anchored Group A Streptococcus (GAS) pilus induces a strong systemic and mucosal immunity in mice. To test the mechanisms behind immunogenicity, we gavaged mice and examined the activation level of various dendritic cells in the intestinal Peyer’s patches and found increased activation of CD11b+CD8− DC compared to wild-type L. lactis, indicating some inherent adjuvant activity of the GAS pilus. As there is evidence that GAS pilus specific antibodies may aid in the protection from GAS infection, we evaluated the ability of our L. lactis vectors to generate these pilus-targeting antibodies. We observed a strong induction of GAS-pilus specific antibodies in both mice and rhesus macaques orally immunized with our L. lactis vectors. We were unable to detect antibody responses generated against the backbone L. lactis bacterium, underlining the immunodominance of the GAS pilus in these vectors. These data suggest that these constructs may serve a dual role in generating protective immune responses against HIV and GAS infections.