Recombinant protein Ag85B-Rv2660c-MPT70 promotes quality of BCG-induced immune response against Mycobacterium tuberculosis H37Ra

Abstract

Introduction: Bacillus Calmette-Guérin (BCG), the only licensed vaccine against Mycobacterium tuberculosis (Mtb) infection, has been extensively used worldwide for over 100 years, but the epidemic of tuberculosis (TB) remains a major challenge to human health and well-being. The quest for a more effective vaccination strategy against the Mtb infection continues. Boosting the protective immunity induced by BCG with recombinant protein is a feasible approach to improve the efficacy of BCG, due to the proven safety and effectiveness of recombinant proteins as vaccination regimes against a variety of infectious diseases. While being shown to be promising in clinical trials in preventing Mtb infection, data suggest this strategy requires further improvement. Methods: In this study, we developed a novel fusion of proteins derived from major antigenic components of Mtb, including Ag85B, Rv2660c, and MPT70 (ARM), and assessed its antigenicity and ability to boost BCG efficacy in a murine model. Results: The results demonstrated that the ARM immunization induced antigen-specific T and B cell responses and reduced the Mtb H37Ra burdens in the lungs and spleen. Mice that were primed with BCG and boosted with the ARM mounted a Th1-type immune response, characterized by an increased proportion of multi-functional ARM- and Mtb lysate-specific CD4+ T cells that produced IFN-γ, TNF-α, and IL-2 compared to BCG alone, and reduced the Mtb burden without the development of severe lung pathological inflammation. Discussion: The results of our study demonstrate that the ARM boost improves the quality of the BCG-induced immune response, increases its potency of pathogen reduction, and offers an additional option for enhancing the efficacy of BCG vaccination.