Characterization of protective immune responses against Neisseria gonorrhoeae induced by intranasal immunization with adhesion and penetration protein

Lingyin Xia; Qin Lu; Xiaosu Wang; Chengyi Jia; Yujie Zhao; Guangli Wang; Jianru Yang; Ningqing Zhang; Xun Min; Jian Huang; Meirong Huang

doi:10.1016/j.heliyon.2024.e25733

Characterization of protective immune responses against Neisseria gonorrhoeae induced by intranasal immunization with adhesion and penetration protein

Heliyon. 2024 Feb 2;10(3):e25733. doi: 10.1016/j.heliyon.2024.e25733. eCollection 2024 Feb 15.

Authors

Lingyin Xia^{1

2}, Qin Lu^{1

2}, Xiaosu Wang^{1

2}, Chengyi Jia^{1

2}, Yujie Zhao^{1

2}, Guangli Wang^{1

2}, Jianru Yang^{1

2}, Ningqing Zhang^{1

2}, Xun Min^{1

2}, Jian Huang^{1

2}, Meirong Huang³

Affiliations

¹ Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
² School of Laboratory Medicine, Zunyi Medical University, Zunyi, Guizhou, China.
³ Department of Blood Transfusion, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

Abstract

Drug-resistant N. gonorrhoeae is an urgent threat to global public health, and vaccine development is the best long-term strategy for controlling gonorrhea. We have previously shown that adhesion and penetration protein (App) play a role in the adhesion, invasion, and reproductive tract colonization of N. gonorrhoeae. Here, we describe the immune response induced by intranasal immunization with passenger and translocator fragments of App. The recombinant App passenger and translocator fragments induced high titers of IgG and IgA antibodies in serum and vaginal washes. Antibodies produced by App passenger and the combination of passenger and translocator mediated the killing of N. gonorrhoeae via serum bactericidal activity and opsonophagocytic activity, whereas antisera from translocator-immunized groups had lower bactericidal activity and opsonophagocytic activity. The antisera of the App passenger and translocator, alone and in combination, inhibited the adhesion of N. gonorrhoeae to cervical epithelial cells in a concentration-dependent manner. Nasal immunization with App passenger and translocator fragments alone or in combination induced high levels of IgG1, IgG2a, and IgG2b antibodies and stimulated mouse splenocytes to secrete cytokines IFN-γ and IL-17A, suggesting that Th1 and Th17 cellular immune responses were activated. In vivo experiments have shown that immune App passenger and transporter fragments can accelerate the clearance of N. gonorrhoeae in the vagina of mice. These data suggest that the App protein is a promising N. gonorrhoeae vaccine antigen.

Keywords: Adhesion and penetration protein; Bactericidal activity; Intranasal immunization; Neisseria gonorrhoeae; Opsonophagocytic activity.