A recombinant BCG-based vaccine against the human respiratory syncytial virus induces a balanced cellular immune response against viral and mycobacterial antigens

ABSTRACT BACKGROUND The human respiratory syncytial virus (hRSV) is a respiratory pathogen responsible for most cases of acute lower respiratory tract infections in infants worldwide. Although this virus represents a significant social and economic burden, there are no safe and effective available vaccines. rBCG-N-hRSV is a vaccine candidate consisting of a recombinant attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) expressing the nucleoprotein of hRSV (N-hRSV). METHODS rBCG-N-hRSV was applied intradermally in three different doses (5×10 3 , 5×10 4 , or 1×10 5 CFU) to healthy adults enrolled in a randomized, double-blind, dose-escalating phase 1 clinical trial ( NCT03213405 ). Blood samples were taken before and at various time points after immunization. Cellular and humoral immune parameters were assessed by analyzing circulating immune cells and sera, respectively. RESULTS Perforin- and Granzyme B-producing PBMCs recognizing viral or mycobacterial antigens were found to increase after immunization with rBCG-N-hRSV. These cells also upregulated IFN-γ and IL-10 secretion in response to N-hRSV and upregulated IFN-γ, IL-6, and TNF-α secretion in response to mycobacterial proteins. While naïve T cell populations contracted over time, no specific memory T cell subset expanded significantly. Although binding to C1q by anti-N-hRSV or anti-mycobacterial antibodies decreased slightly after immunization, no apparent changes were found in the concentration of IgG subclasses against N-hRSV or mycobacterial antigens. CONCLUSIONS The immune response elicited by immunization with rBCG-N-hRSV consists mainly of antigen-specific T cells. The data reported here provide novel information about the characteristics of the immune response elicited after immunization with rBCG-N-hRSV, supporting the safety and immunogenicity of this vaccine.