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

Zhu, Tianmou; McClure, Ryan S.; Harrison, Odile B.; Genco, Caroline; Massari, Paola

doi:10.3390/vaccines7040153

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

Journal Article · Thu Oct 17 00:00:00 EDT 2019 · Vaccines

DOI:https://doi.org/10.3390/vaccines7040153· OSTI ID:1574883

Zhu, Tianmou ^[1]; McClure, Ryan S. ^[2];

^[3]; Genco, Caroline ^[1];

^[1]

Tufts Univ. School of Medicine, Boston, MA (United States). Dept. of Immunology
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Biological Sciences Div.
Univ. of Oxford (United Kingdom). Dept. of Zoology

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.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1574883

Report Number(s):: PNNL-SA-146316; VBSABP

Journal Information:: Vaccines, Vol. 7, Issue 4; ISSN 2076-393X

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 6 works

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MetQ of Neisseria gonorrhoeae Is a Surface-Expressed Antigen That Elicits Bactericidal and Functional Blocking Antibodies Semchenko, Evgeny A.; Day, Christopher J.; Seib, Kate L. Infection and Immunity, Vol. 85, Issue 2 https://doi.org/10.1128/iai.00898-16	journal	November 2016
Heptose I Glycan Substitutions on Neisseria gonorrhoeae Lipooligosaccharide Influence C4b-Binding Protein Binding and Serum Resistance Ram, S.; Ngampasutadol, J.; Cox, A. D. Infection and Immunity, Vol. 75, Issue 8 https://doi.org/10.1128/iai.01109-06	journal	May 2007
Novel Protein Substrates of the Phospho-Form Modification System in Neisseria gonorrhoeae and Their Connection to O -Linked Protein Glycosylation Anonsen, Jan Haug; Egge-Jacobsen, Wolfgang; Aas, Finn Erik Infection and Immunity, Vol. 80, Issue 1 https://doi.org/10.1128/iai.05920-11	journal	November 2011
Phenotypic Characterization of a copA Mutant of Neisseria gonorrhoeae Identifies a Link between Copper and Nitrosative Stress Djoko, Karrera Y.; Franiek, Jessica A.; Edwards, Jennifer L. Infection and Immunity, Vol. 80, Issue 3 https://doi.org/10.1128/iai.06163-11	journal	December 2011
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