Intranasal bovine β-defensin-5 enhances antituberculosis immunity in a mouse model by a novel protein-based respiratory mucosal vaccine

ABSTRACT

Respiratory mucosal immunization is an effective immunization strategy against tuberculosis (TB), and effective mucosal vaccines require adjuvants that can promote protective immunity without deleterious inflammation. Mucosal BCG (Bacille Calmette-Guerin) is effective, but it causes a severe inflammatory response in the lung. A novel less cytotoxic mucosal vaccine AH-PB containing Mycobacterium tuberculosis (Mtb) cell surface antigens Ag85A and HspX (AH), as well as polyinosinic-polycytidylic acid (Poly IC) and bovine neutrophil β-defensin-5 (B5) adjuvants were prepared, with the overarching goal of protecting against TB. Then, the immunogenicity and protective efficacy of these vaccines via the intranasal route were evaluated in a mouse model. Results showed that intranasal AH-PB promoted tissue-resident memory T cells (T_RMs) development in the lung, induced antigen-specific antibody response in airway, provided protection against Mycobacterium bovis (M. bovis), conferred better protection than parenteral BCG in the later stage of infection, and boosted the protective immunity generated by BCG in mice. Moreover, both B5 and Poly IC were indispensable for the protection generated by AH-PB. Furthermore, intranasal immunization with AH-B5 fusion vaccines also provided similar protection against M. bovis compared to AH-PB. Collectively, B5-based TB vaccine via the intranasal route is a promising immunization strategy against bovine TB, and this kind of immunization strategy may be applied to human TB vaccine development. These findings highlight the potential importance of B5 as a mucosal adjuvant used in TB vaccines or other respiratory disease vaccines.

KEYWORDS:

• Tuberculosis
• bovine β-defensin-5
• mucosal immunization
• T_RM
• antibody response

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Z.L. and X.Z. prepared the manuscript. Z.L., X.Z. and H.L designed experiments. Z.L. performed experiments. M.Q., Y.L., Y.W., and H.W. assisted to complete experiments and contributed to acquisition of date. Y.D., Y.C. and Y.G. assisted to complete experiments. All authors contributed to date analysis.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request ([email protected]).

Additional information

Funding

This research was supported by the National Natural Science Foundation of China [Project No.31873005], National Key Research and Development Program [Project No. 2021YFD1800405]; and The High-end Foreign Experts Recruitment Program [Project No. GDW20161100071].