Shuyi Wang1, Juan Xue1, Ping Lu1, Chunshan Ni1, Hao Cheng2, Rui Han2, Stijn van der Veen3. 1. Department of Microbiology and Parasitology, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China. 2. Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 Qingchun East Road, Hangzhou 310020, China. 3. Department of Microbiology and Parasitology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China . Electronic address: stijnvanderveen@zju.edu.cn.
Abstract
OBJECTIVES: The rise in multidrug resistant Neisseria gonorrhoeae poses a threat to healthcare, while the development of an effective vaccine has remained elusive due to antigenic and phase variability of surface-expressed proteins. In the current study, we identified a fully conserved surface expressed protein and characterized its suitability as a vaccine antigen. METHODS: An in silico approach was used to predict surface-expressed proteins and analyze sequence conservation and phase variability. The most conserved protein and its surface-exposed Loop 2, which was displayed as both a structural and linear epitope on the oligomerization domain of C4b binding protein, were used to immunize mice. Immunogenicity was subsequently analyzed by determination of antibody titers and serum bactericidal activity. RESULTS: MtrE was identified as one of the most conserved surface-expressed proteins. Furthermore, MtrE and both Loop 2-containing fusion proteins elicited high protein-specific antibody titers and particularly the two Loop 2 fusion proteins showed high anti-Loop 2 titers. In addition, antibodies raised against all three proteins were able to recognize MtrE expressed on the surface of N. gonorrhoeae and showed high MtrE-dependent bactericidal activity. CONCLUSIONS: Our results show that MtrE and Loop 2 are promising novel conserved surface-expressed antigens for vaccine development against N. gonorrhoeae.
OBJECTIVES: The rise in multidrug resistant Neisseria gonorrhoeae poses a threat to healthcare, while the development of an effective vaccine has remained elusive due to antigenic and phase variability of surface-expressed proteins. In the current study, we identified a fully conserved surface expressed protein and characterized its suitability as a vaccine antigen. METHODS: An in silico approach was used to predict surface-expressed proteins and analyze sequence conservation and phase variability. The most conserved protein and its surface-exposed Loop 2, which was displayed as both a structural and linear epitope on the oligomerization domain of C4b binding protein, were used to immunize mice. Immunogenicity was subsequently analyzed by determination of antibody titers and serum bactericidal activity. RESULTS: MtrE was identified as one of the most conserved surface-expressed proteins. Furthermore, MtrE and both Loop 2-containing fusion proteins elicited high protein-specific antibody titers and particularly the two Loop 2 fusion proteins showed high anti-Loop 2 titers. In addition, antibodies raised against all three proteins were able to recognize MtrE expressed on the surface of N. gonorrhoeae and showed high MtrE-dependent bactericidal activity. CONCLUSIONS: Our results show that MtrE and Loop 2 are promising novel conserved surface-expressed antigens for vaccine development against N. gonorrhoeae.
Authors: Kathryn A Matthias; Kristie L Connolly; Afrin A Begum; Ann E Jerse; Andrew N Macintyre; Gregory D Sempowski; Margaret C Bash Journal: J Infect Dis Date: 2022-02-15 Impact factor: 7.759
Authors: Sunita Gulati; Michael W Pennington; Andrzej Czerwinski; Darrick Carter; Bo Zheng; Nancy A Nowak; Rosane B DeOliveira; Jutamas Shaughnessy; George W Reed; Sanjay Ram; Peter A Rice Journal: mBio Date: 2019-11-05 Impact factor: 7.867
Authors: Kevin C Ma; Tatum D Mortimer; Allison L Hicks; Nicole E Wheeler; Leonor Sánchez-Busó; Daniel Golparian; George Taiaroa; Daniel H F Rubin; Yi Wang; Deborah A Williamson; Magnus Unemo; Simon R Harris; Yonatan H Grad Journal: Nat Commun Date: 2020-08-17 Impact factor: 14.919