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

Abstract

ABSTRACTBACKGROUNDThe 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).METHODSrBCG-N-hRSV was applied intradermally in three different doses (5×103, 5×104, or 1×105 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.RESULTSPerforin- 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.CONCLUSIONSThe 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.