The humoral immune response elicited upon immunization with recombinant BCG vaccines protects against hRSV and hMPV in a murine preclinical model

Abstract

Abstract Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are among the main etiological agents responsible of acute lower respiratory tract infections in vulnerable populations worldwide. Despite their clinical relevance, the licensing of a safe and effective vaccine has not been achieved. Considering this, our laboratory developed two different recombinant Mycobacterium bovis BCG strains as vaccine candidates. These recombinant BCGs express either the hRSV-Nucleoprotein (rBCG-N) or the hMPV-Phosphoprotein (rBCG-P). Both vaccines prototypes were able to promote cellular protection against their respective virus. However, the humoral response elicited upon immunization with these vaccines has not been characterized. Here we show that, upon immunization and challenge of mice with the respective rBCG and virus, the induced humoral response was able to protect against the viral infection, promoting the secretion of specific antibodies against each virus and several of their proteins, as measured in sera samples by ELISA assays. We also described that immunization and challenge promoted the induction of antibodies with enhanced neutralizing capacities, as seen during in vitro assays. Moreover, we show that sera transferred from immunized and challenged mice into naïve mice is enough to protect from the infection, when these naïve mice were challenged with the viruses. This protection was characterized by a decreased in the viral replication and pulmonary disease. These results support the notion that the use of rBCG vectors could be an effective vaccine platform against these two major respiratory pathogens and places our vaccine candidates as suitable approaches for the treatment against both hRSV and hMPV.