mRNA Nanovaccine Against Mycobacterium tuberculosis Elicits Robust Immunity in Mice

Abstract

Background

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains a major global health concern. Despite the availability of Bacillus Calmette-Guérin (BCG) vaccine, there is an urgent need for more effective TB vaccines. Here, we developed an mRNA nanoadjuvant vaccine targeting key M.tb antigens and evaluated its immunogenicity and protective efficacy in a murine model.

Methods

C57BL/6 mice (N=15/group) were immunized with a two-dose regimen of 10 µg mRNA encoding Ag85B, Hsp70, and ESAT-6 at 4-week intervals through the subcutaneous or intranasal routes. Mice vaccinated with PBS or BCG served as unvaccinated and positive controls, respectively. The immunogenicity and protective immunity of the vaccine were evaluated by stimulating splenocytes and lung cells with M.tb purified protein derivative (PPD), Ag85B, and HSP70 purified proteins. Cellular immune responses were assessed by flow cytometry.

Results

The mRNA nanoadjuvant vaccine elicited robust cellular and humoral immune responses in immunized mice comparable to BCG. Elevated levels of antigen-specific IgG antibodies were detected post-immunization. Additionally, significant IFN-γ, TNF-a, IL-17A, and IL-2 production by antigen-specific T cells was observed. Overall, mRNA nanovaccines induce robust T cell responses characterized by activation of both memory and effector T cell populations that are polyfunctional.

Discussion

Our findings highlight the potential of the mRNA nanoadjuvant vaccine encoding immunogenic antigens as a promising candidate for TB vaccine development. This vaccine robustly elicited an immune profile that is known to be protective against M.tb infection in both animals and humans. Further studies are warranted to optimize the vaccine formulation and evaluate its long-term protective efficacy and safety in larger animal models and clinical trials.

Conclusion

This study elucidates the promising immunogenicity of mRNA vaccines encoding M.tb immunodominant antigens in mice, with adjuvant and diverse administration routes significantly enhancing vaccine immunogenicity. The absence of adverse effects on mice body weight, combined with superior immune responses, validates the effectiveness of this vaccination strategy against M.tb. Future research endeavors should focus on evaluating the vaccine's performance in more relevant models of M.tb infection, such as non-human primates, and assessing its potential to prevent TB disease.