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Title: Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection

Abstract

There is an increasingly severe trend of antibiotic-resistant Neisseria gonorrhoeae strains worldwide and new therapeutic strategies are needed against this sexually-transmitted pathogen. Despite the urgency, progress towards a gonococcal vaccine has been slowed by a scarcity of suitable antigens, lack of correlates of protection in humans and limited animal models of infection. N. gonorrhoeae gene expression levels in the natural human host does not reflect expression in vitro, further complicating in vitro-basedvaccine analysis platforms. We designed a novel candidate antigen selection strategy (CASS), based on a reverse vaccinology-like approach coupled with bioinformatics. We utilized the CASS to mine gonococcal proteins expressed during human mucosal infection, reported in our previous studies, and focused on a large pool of hypothetical proteins as an untapped source of potential new antigens. Via two discovery and analysis phases (DAP), we identified 36 targets predicted to be immunogenic, membrane-associated proteins conserved in N. gonorrhoeae and suitable for recombinant expression. Six initial candidates were produced and used to immunize mice. Characterization of the immune responses indicated cross-reactive antibodies and serum bactericidal activity against different N. gonorrhoeae strains. These results support the CASS as a tool for the discovery of new vaccine candidates.

Authors:
 [1];  [2]; ORCiD logo [3];  [1]; ORCiD logo [1]
  1. Tufts Univ. School of Medicine, Boston, MA (United States). Dept. of Immunology
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Biological Sciences Div.
  3. Univ. of Oxford (United Kingdom). Dept. of Zoology
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1574883
Report Number(s):
PNNL-SA-146316
Journal ID: ISSN 2076-393X; VBSABP
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
Vaccines
Additional Journal Information:
Journal Volume: 7; Journal Issue: 4; Journal ID: ISSN 2076-393X
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; gonorrhea; vaccine; in silicoanalysis; hypothetical proteins; bactericidal antibodies

Citation Formats

Zhu, Tianmou, McClure, Ryan S., Harrison, Odile B., Genco, Caroline, and Massari, Paola. Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection. United States: N. p., 2019. Web. doi:10.3390/vaccines7040153.
Zhu, Tianmou, McClure, Ryan S., Harrison, Odile B., Genco, Caroline, & Massari, Paola. Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection. United States. doi:10.3390/vaccines7040153.
Zhu, Tianmou, McClure, Ryan S., Harrison, Odile B., Genco, Caroline, and Massari, Paola. Thu . "Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection". United States. doi:10.3390/vaccines7040153. https://www.osti.gov/servlets/purl/1574883.
@article{osti_1574883,
title = {Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection},
author = {Zhu, Tianmou and McClure, Ryan S. and Harrison, Odile B. and Genco, Caroline and Massari, Paola},
abstractNote = {There is an increasingly severe trend of antibiotic-resistant Neisseria gonorrhoeae strains worldwide and new therapeutic strategies are needed against this sexually-transmitted pathogen. Despite the urgency, progress towards a gonococcal vaccine has been slowed by a scarcity of suitable antigens, lack of correlates of protection in humans and limited animal models of infection. N. gonorrhoeae gene expression levels in the natural human host does not reflect expression in vitro, further complicating in vitro-basedvaccine analysis platforms. We designed a novel candidate antigen selection strategy (CASS), based on a reverse vaccinology-like approach coupled with bioinformatics. We utilized the CASS to mine gonococcal proteins expressed during human mucosal infection, reported in our previous studies, and focused on a large pool of hypothetical proteins as an untapped source of potential new antigens. Via two discovery and analysis phases (DAP), we identified 36 targets predicted to be immunogenic, membrane-associated proteins conserved in N. gonorrhoeae and suitable for recombinant expression. Six initial candidates were produced and used to immunize mice. Characterization of the immune responses indicated cross-reactive antibodies and serum bactericidal activity against different N. gonorrhoeae strains. These results support the CASS as a tool for the discovery of new vaccine candidates.},
doi = {10.3390/vaccines7040153},
journal = {Vaccines},
number = 4,
volume = 7,
place = {United States},
year = {2019},
month = {10}
}

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