DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

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 Laboratory (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
Publisher:
MDPI
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. https://doi.org/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. https://doi.org/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 = {Thu Oct 17 00:00:00 EDT 2019},
month = {Thu Oct 17 00:00:00 EDT 2019}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 6 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Experimental vaccine induces Th1-driven immune responses and resistance to Neisseria gonorrhoeae infection in a murine model
text, January 2017

  • ,
  • The University of North Carolina at Chapel Hill University Libraries
  • DOI: 10.17615/ksr2-mm15

Gonorrhoea reinfection in heterosexual STD clinic attendees: longitudinal analysis of risks for first reinfection
journal, April 2003


Subversion of nutritional immunity by the pathogenic Neisseriae
journal, October 2017


The  -Barrel Outer Membrane Protein Assembly Complex of Neisseria meningitidis
journal, September 2009

  • Volokhina, E. B.; Beckers, F.; Tommassen, J.
  • Journal of Bacteriology, Vol. 191, Issue 22
  • DOI: 10.1128/JB.00737-09

KEGG: Kyoto Encyclopedia of Genes and Genomes
journal, January 2000

  • Kanehisa, Minoru; Goto, Susumu
  • Nucleic Acids Research, Vol. 28, Issue 1, p. 27-30
  • DOI: 10.1093/nar/28.1.27

Fur-Mediated Global Regulatory Circuits in Pathogenic Neisseria Species
journal, August 2012

  • Yu, Chunxiao; Genco, Caroline Attardo
  • Journal of Bacteriology, Vol. 194, Issue 23
  • DOI: 10.1128/JB.00262-12

A Meningococcal Native Outer Membrane Vesicle Vaccine With Attenuated Endotoxin and Overexpressed Factor H Binding Protein Elicits Gonococcal Bactericidal Antibodies
journal, October 2018

  • Beernink, Peter T.; Ispasanie, Emma; Lewis, Lisa A.
  • The Journal of Infectious Diseases, Vol. 219, Issue 7
  • DOI: 10.1093/infdis/jiy609

Feature-based prediction of non-classical and leaderless protein secretion
journal, May 2004

  • Bendtsen, J. D.; Jensen, L. J.; Blom, N.
  • Protein Engineering Design and Selection, Vol. 17, Issue 4
  • DOI: 10.1093/protein/gzh037

Experimental vaccine induces Th1-driven immune responses and resistance to Neisseria gonorrhoeae infection in a murine model
journal, March 2017

  • Liu, Y.; Hammer, L. A.; Liu, W.
  • Mucosal Immunology, Vol. 10, Issue 6
  • DOI: 10.1038/mi.2017.11

Bacterial copper storage proteins
journal, February 2018

  • Dennison, Christopher; David, Sholto; Lee, Jaeick
  • Journal of Biological Chemistry, Vol. 293, Issue 13
  • DOI: 10.1074/jbc.TM117.000180

Targeting Lipooligosaccharide (LOS) for a Gonococcal Vaccine
journal, February 2019


Testing the '+2 rule' for lipoprotein sorting in the Escherichia coli cell envelope with a new genetic selection
journal, November 1999


Innate Nutritional Immunity
journal, June 2018

  • Núñez, Gabriel; Sakamoto, Kei; Soares, Miguel P.
  • The Journal of Immunology, Vol. 201, Issue 1
  • DOI: 10.4049/jimmunol.1800325

Identification of Novel Immunogenic Proteins of Neisseria gonorrhoeae by Phage Display
journal, February 2016


Dynamic Association of BAM Complex Modules Includes Surface Exposure of the Lipoprotein BamC
journal, September 2012

  • Webb, Chaille T.; Selkrig, Joel; Perry, Andrew J.
  • Journal of Molecular Biology, Vol. 422, Issue 4
  • DOI: 10.1016/j.jmb.2012.05.035

BIGSdb: Scalable analysis of bacterial genome variation at the population level
journal, December 2010


SignalP 5.0 improves signal peptide predictions using deep neural networks
journal, February 2019

  • Almagro Armenteros, José Juan; Tsirigos, Konstantinos D.; Sønderby, Casper Kaae
  • Nature Biotechnology, Vol. 37, Issue 4
  • DOI: 10.1038/s41587-019-0036-z

Prediction of lipoprotein signal peptides in Gram-negative bacteria
journal, August 2003

  • Juncker, Agnieszka S.; Willenbrock, Hanni; von Heijne, Gunnar
  • Protein Science, Vol. 12, Issue 8
  • DOI: 10.1110/ps.0303703

The Gonococcal Transcriptome during Infection of the Lower Genital Tract in Women
journal, August 2015


A universal vaccine for serogroup B meningococcus
journal, July 2006

  • Giuliani, M. M.; Adu-Bobie, J.; Comanducci, M.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 29
  • DOI: 10.1073/pnas.0603940103

In-silico Hierarchical Approach for the Identification of Potential Universal Vaccine Candidates (PUVCs) from Neisseria gonorrhoeae
journal, December 2016


The novel interaction between Neisseria gonorrhoeae TdfJ and human S100A7 allows gonococci to subvert host zinc restriction
journal, August 2019


VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines
journal, January 2007

  • Doytchinova, Irini A.; Flower, Darren R.
  • BMC Bioinformatics, Vol. 8, Issue 1
  • DOI: 10.1186/1471-2105-8-4

The reproductive cycle is a pathogenic determinant during gonococcal pelvic inflammatory disease in mice
journal, December 2015

  • Islam, E. A.; Shaik-Dasthagirisaheb, Y.; Kaushic, C.
  • Mucosal Immunology, Vol. 9, Issue 4
  • DOI: 10.1038/mi.2015.122

Structural and Immunological Characterization of Novel Recombinant MOMP-Based Chlamydial Antigens
journal, December 2017


Neisserial surface lipoproteins: structure, function and biogenesis
journal, February 2017

  • Hooda, Yogesh; Shin, Hyejin E.; Bateman, Thomas J.
  • Pathogens and Disease, Vol. 75, Issue 2
  • DOI: 10.1093/femspd/ftx010

Proteomic analysis of a meningococcal outer membrane vesicle vaccine prepared from the group B strain NZ98/254
journal, July 2006


Intranasal Immunization with Gonococcal Outer Membrane Preparations Reduces the Duration of Vaginal Colonization of Mice by Neisseria gonorrhoeae
journal, September 2000

  • Plante, Martin; Jerse, Ann; Hamel, Josée
  • The Journal of Infectious Diseases, Vol. 182, Issue 3
  • DOI: 10.1086/315801

Experimental Gonococcal Infection in Male Volunteers: Cumulative Experience with Neisseria gonorrhoeae Strains FA1090 and MS11mkC
text, January 2011

  • M., Hobbs, Marcia; M., Shafer, William; Frederick, Sparling, P.
  • The University of North Carolina at Chapel Hill University Libraries
  • DOI: 10.17615/mc3m-n146

Recombinant bacterial lipoproteins as vaccine candidates
journal, September 2015


The Serogroup B Meningococcal Vaccine Bexsero Elicits Antibodies to Neisseria gonorrhoeae
journal, December 2018

  • Semchenko, Evgeny A.; Tan, Aimee; Borrow, Ray
  • Clinical Infectious Diseases, Vol. 69, Issue 7
  • DOI: 10.1093/cid/ciy1061

Identification of new meningococcal serogroup B surface antigens through a systematic analysis of neisserial genomes
journal, December 2009


Predicting transmembrane protein topology with a hidden markov model: application to complete genomes11Edited by F. Cohen
journal, January 2001

  • Krogh, Anders; Larsson, Björn; von Heijne, Gunnar
  • Journal of Molecular Biology, Vol. 305, Issue 3
  • DOI: 10.1006/jmbi.2000.4315

Basic local alignment search tool
journal, October 1990

  • Altschul, Stephen F.; Gish, Warren; Miller, Webb
  • Journal of Molecular Biology, Vol. 215, Issue 3, p. 403-410
  • DOI: 10.1016/S0022-2836(05)80360-2

DeepLoc: prediction of protein subcellular localization using deep learning
journal, July 2017

  • Almagro Armenteros, José Juan; Sønderby, Casper Kaae; Sønderby, Søren Kaae
  • Bioinformatics, Vol. 33, Issue 21
  • DOI: 10.1093/bioinformatics/btx431

Identification of novel immunogenic proteins of Neisseria gonorrhoeae by phage display
text, January 2019


Copper(II)-Induced Restructuring of ZnuD, a Zinc(II) Transporter from Neisseria meningitidis
journal, April 2019

  • Hecel, Aleksandra; RowiÅ„ska-Å»yrek, Magdalena; KozÅ‚owski, Henryk
  • Inorganic Chemistry, Vol. 58, Issue 9
  • DOI: 10.1021/acs.inorgchem.9b00265

Lipoprotein NMB0928 from Neisseria meningitidis serogroup B as a novel vaccine candidate
journal, December 2007


Environmental dissemination of pathogenic Listeria monocytogenes in flowing surface waters in Switzerland
journal, April 2021


Experimental Gonococcal Urethritis and Reinfection with Homologous Gonococci in Male Volunteers
journal, January 2001


Insights into the regulation of protein abundance from proteomic and transcriptomic analyses
journal, March 2012

  • Vogel, Christine; Marcotte, Edward M.
  • Nature Reviews Genetics, Vol. 13, Issue 4
  • DOI: 10.1038/nrg3185

Gneg-mPLoc: A top-down strategy to enhance the quality of predicting subcellular localization of Gram-negative bacterial proteins
journal, May 2010


Recombinant protein meningococcal serogroup B vaccine combined with outer membrane vesicles
journal, May 2011


Topological analysis of protein co-abundance networks identifies novel host targets important for HCV infection and pathogenesis
journal, January 2012

  • McDermott, Jason E.; Diamond, Deborah L.; Corley, Courtney
  • BMC Systems Biology, Vol. 6, Issue 1
  • DOI: 10.1186/1752-0509-6-28

Antimicrobial Resistance Expressed by Neisseria gonorrhoeae: A Major Global Public Health Problem in the 21st Century
journal, June 2016


Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand: a retrospective case-control study
journal, September 2017


Broad spectrum O-linked protein glycosylation in the human pathogen Neisseria gonorrhoeae
journal, February 2009

  • Vik, A.; Aas, F. E.; Anonsen, J. H.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 11
  • DOI: 10.1073/pnas.0809504106

A genetic screen identifies genes and sites involved in pilin antigenic variation in Neisseria gonorrhoeae : Gonococcal mutants with impaired pilin variation
journal, June 2005


Antibody to Rmp (outer membrane protein 3) increases susceptibility to gonococcal infection.
journal, January 1993

  • Plummer, F. A.; Chubb, H.; Simonsen, J. N.
  • Journal of Clinical Investigation, Vol. 91, Issue 1
  • DOI: 10.1172/JCI116190

Neisseria gonorrhoeae : Drug Resistance, Mouse Models, and Vaccine Development
journal, September 2017


Utility of Hybrid Transferrin Binding Protein Antigens for Protection Against Pathogenic Neisseria Species
journal, February 2019


Regulation of IL-10 and IL-12 production and function in macrophages and dendritic cells
journal, January 2015


Proteomic analysis of a meningococcal outer membrane vesicle vaccine prepared from the group B strain NZ98/254
journal, June 2006


Meningococcal B vaccine (4CMenB): the journey from research to real world experience
journal, December 2018


Advantages of combined transmembrane topology and signal peptide prediction--the Phobius web server
journal, May 2007

  • Kall, L.; Krogh, A.; Sonnhammer, E. L. L.
  • Nucleic Acids Research, Vol. 35, Issue Web Server
  • DOI: 10.1093/nar/gkm256

PredictProtein—an open resource for online prediction of protein structural and functional features
journal, May 2014

  • Yachdav, Guy; Kloppmann, Edda; Kajan, Laszlo
  • Nucleic Acids Research, Vol. 42, Issue W1
  • DOI: 10.1093/nar/gku366

Molecular Typing of Neisseria gonorrhoeae Causing Repeated Infections: Evolution of Porin during Passage within a Community
journal, February 1999

  • Hobbs, Marcia M.; Alcorn, Timothy M.; Davis, Rachael H.
  • The Journal of Infectious Diseases, Vol. 179, Issue 2
  • DOI: 10.1086/314608

Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer
journal, January 2014


Estradiol-Treated Female Mice as Surrogate Hosts for Neisseria gonorrhoeae Genital Tract Infections
journal, January 2011


Gonococcal pilin variants in experimental gonorrhea
journal, May 1987


Binding of C4b-Binding Protein to Porin: A Molecular Mechanism of Serum Resistance of
journal, January 2001

  • Ram, Sanjay; Cullinane, Meabh; Blom, Anna M.
  • The Journal of Experimental Medicine, Vol. 193, Issue 3
  • DOI: 10.1084/jem.193.3.281

The Pfam protein families database in 2019
journal, October 2018

  • El-Gebali, Sara; Mistry, Jaina; Bateman, Alex
  • Nucleic Acids Research, Vol. 47, Issue D1
  • DOI: 10.1093/nar/gky995

Copper tolerance and virulence in bacteria
journal, January 2015

  • Ladomersky, Erik; Petris, Michael J.
  • Metallomics, Vol. 7, Issue 6
  • DOI: 10.1039/C4MT00327F

UniProt: a worldwide hub of protein knowledge
November 2018


Updates on the web-based VIOLIN vaccine database and analysis system
journal, November 2013

  • He, Yongqun; Racz, Rebecca; Sayers, Samantha
  • Nucleic Acids Research, Vol. 42, Issue D1
  • DOI: 10.1093/nar/gkt1133

Gonococcal transferrin binding protein chimeras induce bactericidal and growth inhibitory antibodies in mice
journal, October 2007


Proteomics, Bioinformatics and Structure-Function Antigen Mining For Gonorrhea Vaccines
journal, December 2018

  • Baarda, Benjamin I.; Martinez, Fabian G.; Sikora, Aleksandra E.
  • Frontiers in Immunology, Vol. 9
  • DOI: 10.3389/fimmu.2018.02793

Nasal Inoculation of the Commensal Neisseria lactamica Inhibits Carriage of Neisseria meningitidis by Young Adults: A Controlled Human Infection Study
journal, April 2015

  • Deasy, Alice M.; Guccione, Ed; Dale, Adam P.
  • Clinical Infectious Diseases, Vol. 60, Issue 10
  • DOI: 10.1093/cid/civ098

Suppression of host adaptive immune responses by Neisseria gonorrhoeae: role of interleukin 10 and type 1 regulatory T cells
journal, June 2013

  • Liu, Y.; Liu, W.; Russell, M. W.
  • Mucosal Immunology, Vol. 7, Issue 1
  • DOI: 10.1038/mi.2013.36

Pathogenesis of Neisseria gonorrhoeae and the Host Defense in Ascending Infections of Human Fallopian Tube
journal, November 2018


From Chaperones to the Membrane with a BAM!
journal, October 2016


A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria
journal, September 2015

  • Jen, Freda E. -C.; Djoko, Karrera Y.; Bent, Stephen J.
  • The FASEB Journal, Vol. 29, Issue 9
  • DOI: 10.1096/fj.15-270751

Immunogenicity profiling of protein antigens from capsular group B Neisseria meningitidis
journal, May 2019


Neisseria meningitidis: pathogenesis and immunity
journal, February 2015


An Outer Membrane Receptor of Neisseria meningitidis Involved in Zinc Acquisition with Vaccine Potential
journal, July 2010


Experimental Gonococcal Infection in Male Volunteers: Cumulative Experience with Neisseria gonorrhoeae Strains FA1090 and MS11mkC
journal, January 2011

  • Hobbs, Marcia M.; Sparling, P. Frederick; Cohen, Myron S.
  • Frontiers in Microbiology, Vol. 2
  • DOI: 10.3389/fmicb.2011.00123

Solubilization of the Cytoplasmic Membrane of Escherichia coli by the Ionic Detergent Sodium-Lauryl Sarcosinate
journal, September 1973


Multiple gonococcal pilin antigenic variants are produced during experimental human infections.
text, January 1994

  • J., Wright, C.; E., Jerse, A.; S., Seifert, H.
  • The University of North Carolina at Chapel Hill University Libraries
  • DOI: 10.17615/4hka-fg62

Proteomic analysis of a meningococcal outer membrane vesicle vaccine prepared from the group B strain NZ98/254
journal, July 2006


Predicting transmembrane protein topology with a hidden markov model: application to complete genomes11Edited by F. Cohen
journal, January 2001

  • Krogh, Anders; Larsson, Björn; von Heijne, Gunnar
  • Journal of Molecular Biology, Vol. 305, Issue 3
  • DOI: 10.1006/jmbi.2000.4315

Efficacy trial of a parenteral gonococcal pilus vaccine in men
journal, March 1991


In-silico Hierarchical Approach for the Identification of Potential Universal Vaccine Candidates (PUVCs) from Neisseria gonorrhoeae
journal, December 2016


Neisseria meningitidis: pathogenesis and immunity
journal, February 2015


From Chaperones to the Membrane with a BAM!
journal, October 2016


Gonococcal transferrin binding protein chimeras induce bactericidal and growth inhibitory antibodies in mice
journal, October 2007


Lipoprotein NMB0928 from Neisseria meningitidis serogroup B as a novel vaccine candidate
journal, December 2007


Identification of new meningococcal serogroup B surface antigens through a systematic analysis of neisserial genomes
journal, December 2009


Gonorrhoea vaccines: a step in the right direction
journal, September 2017


Copper(II)-Induced Restructuring of ZnuD, a Zinc(II) Transporter from Neisseria meningitidis
journal, April 2019

  • Hecel, Aleksandra; RowiÅ„ska-Å»yrek, Magdalena; KozÅ‚owski, Henryk
  • Inorganic Chemistry, Vol. 58, Issue 9
  • DOI: 10.1021/acs.inorgchem.9b00265

Experimental vaccine induces Th1-driven immune responses and resistance to Neisseria gonorrhoeae infection in a murine model
journal, March 2017

  • Liu, Y.; Hammer, L. A.; Liu, W.
  • Mucosal Immunology, Vol. 10, Issue 6
  • DOI: 10.1038/mi.2017.11

Insights into the regulation of protein abundance from proteomic and transcriptomic analyses
journal, March 2012

  • Vogel, Christine; Marcotte, Edward M.
  • Nature Reviews Genetics, Vol. 13, Issue 4
  • DOI: 10.1038/nrg3185

SignalP 5.0 improves signal peptide predictions using deep neural networks
journal, February 2019

  • Almagro Armenteros, José Juan; Tsirigos, Konstantinos D.; Sønderby, Casper Kaae
  • Nature Biotechnology, Vol. 37, Issue 4
  • DOI: 10.1038/s41587-019-0036-z

Red versus green leaves: transcriptomic comparison of foliar senescence between two Prunus cerasifera genotypes
journal, February 2020


Testing the '+2 rule' for lipoprotein sorting in the Escherichia coli cell envelope with a new genetic selection
journal, November 1999


A universal vaccine for serogroup B meningococcus
journal, July 2006

  • Giuliani, M. M.; Adu-Bobie, J.; Comanducci, M.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 29
  • DOI: 10.1073/pnas.0603940103

Broad spectrum O-linked protein glycosylation in the human pathogen Neisseria gonorrhoeae
journal, February 2009

  • Vik, A.; Aas, F. E.; Anonsen, J. H.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 11
  • DOI: 10.1073/pnas.0809504106

Proteomics-driven Antigen Discovery for Development of Vaccines Against Gonorrhea
journal, May 2016

  • Zielke, Ryszard A.; Wierzbicki, Igor H.; Baarda, Benjamin I.
  • Molecular & Cellular Proteomics, Vol. 15, Issue 7
  • DOI: 10.1074/mcp.m116.058800

Quantitative Proteomics of the 2016 WHO Neisseria gonorrhoeae Reference Strains Surveys Vaccine Candidates and Antimicrobial Resistance Determinants
journal, October 2018

  • El-Rami, Fadi E.; Zielke, Ryszard A.; Wi, Teodora
  • Molecular & Cellular Proteomics, Vol. 18, Issue 1
  • DOI: 10.1074/mcp.ra118.001125

Meningococcal B vaccine (4CMenB): the journey from research to real world experience
journal, December 2018


Gonococcal pilin variants in experimental gonorrhea
journal, May 1987


Molecular Typing of Neisseria gonorrhoeae Causing Repeated Infections: Evolution of Porin during Passage within a Community
journal, February 1999

  • Hobbs, Marcia M.; Alcorn, Timothy M.; Davis, Rachael H.
  • The Journal of Infectious Diseases, Vol. 179, Issue 2
  • DOI: 10.1086/314608

Intranasal Immunization with Gonococcal Outer Membrane Preparations Reduces the Duration of Vaginal Colonization of Mice by Neisseria gonorrhoeae
journal, September 2000

  • Plante, Martin; Jerse, Ann; Hamel, Josée
  • The Journal of Infectious Diseases, Vol. 182, Issue 3
  • DOI: 10.1086/315801

Nasal Inoculation of the Commensal Neisseria lactamica Inhibits Carriage of Neisseria meningitidis by Young Adults: A Controlled Human Infection Study
journal, April 2015

  • Deasy, Alice M.; Guccione, Ed; Dale, Adam P.
  • Clinical Infectious Diseases, Vol. 60, Issue 10
  • DOI: 10.1093/cid/civ098

A Meningococcal Native Outer Membrane Vesicle Vaccine With Attenuated Endotoxin and Overexpressed Factor H Binding Protein Elicits Gonococcal Bactericidal Antibodies
journal, October 2018

  • Beernink, Peter T.; Ispasanie, Emma; Lewis, Lisa A.
  • The Journal of Infectious Diseases, Vol. 219, Issue 7
  • DOI: 10.1093/infdis/jiy609

Updates on the web-based VIOLIN vaccine database and analysis system
journal, November 2013

  • He, Yongqun; Racz, Rebecca; Sayers, Samantha
  • Nucleic Acids Research, Vol. 42, Issue D1
  • DOI: 10.1093/nar/gkt1133

UniProt: a worldwide hub of protein knowledge
November 2018


The Pfam protein families database in 2019
journal, October 2018

  • El-Gebali, Sara; Mistry, Jaina; Bateman, Alex
  • Nucleic Acids Research, Vol. 47, Issue D1
  • DOI: 10.1093/nar/gky995

Feature-based prediction of non-classical and leaderless protein secretion
journal, May 2004

  • Bendtsen, J. D.; Jensen, L. J.; Blom, N.
  • Protein Engineering Design and Selection, Vol. 17, Issue 4
  • DOI: 10.1093/protein/gzh037

A genetic screen reveals a periplasmic copper chaperone required for nitrite reductase activity in pathogenic Neisseria
journal, September 2015

  • Jen, Freda E. -C.; Djoko, Karrera Y.; Bent, Stephen J.
  • The FASEB Journal, Vol. 29, Issue 9
  • DOI: 10.1096/fj.15-270751

Future prospects for new vaccines against sexually transmitted infections
journal, January 2016


Prediction of lipoprotein signal peptides in Gram-negative bacteria
journal, August 2003

  • Juncker, Agnieszka S.; Willenbrock, Hanni; von Heijne, Gunnar
  • Protein Science, Vol. 12, Issue 8
  • DOI: 10.1110/ps.0303703

A genetic screen identifies genes and sites involved in pilin antigenic variation in Neisseria gonorrhoeae : Gonococcal mutants with impaired pilin variation
journal, June 2005


Both MisR (CpxR) and MisS (CpxA) Are Required for Neisseria gonorrhoeae Infection in a Murine Model of Lower Genital Tract Infection
journal, June 2017

  • Gangaiah, Dharanesh; Raterman, Erica L.; Wu, Hong
  • Infection and Immunity, Vol. 85, Issue 9
  • DOI: 10.1128/iai.00307-17

MetQ of Neisseria gonorrhoeae Is a Surface-Expressed Antigen That Elicits Bactericidal and Functional Blocking Antibodies
journal, November 2016

  • Semchenko, Evgeny A.; Day, Christopher J.; Seib, Kate L.
  • Infection and Immunity, Vol. 85, Issue 2
  • DOI: 10.1128/iai.00898-16

Heptose I Glycan Substitutions on Neisseria gonorrhoeae Lipooligosaccharide Influence C4b-Binding Protein Binding and Serum Resistance
journal, May 2007

  • Ram, S.; Ngampasutadol, J.; Cox, A. D.
  • Infection and Immunity, Vol. 75, Issue 8
  • DOI: 10.1128/iai.01109-06

Novel Protein Substrates of the Phospho-Form Modification System in Neisseria gonorrhoeae and Their Connection to O -Linked Protein Glycosylation
journal, November 2011

  • Anonsen, Jan Haug; Egge-Jacobsen, Wolfgang; Aas, Finn Erik
  • Infection and Immunity, Vol. 80, Issue 1
  • DOI: 10.1128/iai.05920-11

Phenotypic Characterization of a copA Mutant of Neisseria gonorrhoeae Identifies a Link between Copper and Nitrosative Stress
journal, December 2011

  • Djoko, Karrera Y.; Franiek, Jessica A.; Edwards, Jennifer L.
  • Infection and Immunity, Vol. 80, Issue 3
  • DOI: 10.1128/iai.06163-11

Structural and Evolutionary Inference from Molecular Variation in Neisseria Porins
journal, May 1999


Analysis of the Regulated Transcriptome of Neisseria meningitidis in Human Blood Using a Tiling Array
journal, September 2012

  • Del Tordello, E.; Bottini, S.; Muzzi, A.
  • Journal of Bacteriology, Vol. 194, Issue 22
  • DOI: 10.1128/jb.01055-12

Identification of Regulatory Elements That Control Expression of the tbpBA Operon in Neisseria gonorrhoeae
journal, May 2014

  • Velez Acevedo, R. N.; Ronpirin, C.; Kandler, J. L.
  • Journal of Bacteriology, Vol. 196, Issue 15
  • DOI: 10.1128/jb.01693-14

Structure of the Recombinant Neisseria gonorrhoeae Adhesin Complex Protein (rNg-ACP) and Generation of Murine Antibodies with Bactericidal Activity against Gonococci
journal, October 2018

  • Almonacid-Mendoza, Hannia Liliana; Humbert, María Victoria; Dijokaite, Aiste
  • mSphere, Vol. 3, Issue 5
  • DOI: 10.1128/msphere.00331-18

Gonorrhoea reinfection in heterosexual STD clinic attendees: longitudinal analysis of risks for first reinfection
journal, April 2003


Neisseria gonorrhoeae : Drug Resistance, Mouse Models, and Vaccine Development
journal, September 2017


Epidemiologic evidence for the development of serovar-specific immunity after gonococcal infection.
journal, May 1989

  • Plummer, F. A.; Simonsen, J. N.; Chubb, H.
  • Journal of Clinical Investigation, Vol. 83, Issue 5
  • DOI: 10.1172/jci114040

Multiple gonococcal pilin antigenic variants are produced during experimental human infections.
journal, June 1994

  • Seifert, H. S.; Wright, C. J.; Jerse, A. E.
  • Journal of Clinical Investigation, Vol. 93, Issue 6
  • DOI: 10.1172/jci117290

BIGSdb: Scalable analysis of bacterial genome variation at the population level
journal, December 2010


VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines
journal, January 2007

  • Doytchinova, Irini A.; Flower, Darren R.
  • BMC Bioinformatics, Vol. 8, Issue 1
  • DOI: 10.1186/1471-2105-8-4

Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer
journal, January 2014


Topological analysis of protein co-abundance networks identifies novel host targets important for HCV infection and pathogenesis
journal, January 2012

  • McDermott, Jason E.; Diamond, Deborah L.; Corley, Courtney
  • BMC Systems Biology, Vol. 6, Issue 1
  • DOI: 10.1186/1752-0509-6-28

Regulation of IL-10 and IL-12 production and function in macrophages and dendritic cells
journal, January 2015


The Gonococcal Transcriptome during Infection of the Lower Genital Tract in Women
journal, August 2015


The novel interaction between Neisseria gonorrhoeae TdfJ and human S100A7 allows gonococci to subvert host zinc restriction
journal, August 2019


Recombinant protein meningococcal serogroup B vaccine combined with outer membrane vesicles
journal, May 2011


Recombinant bacterial lipoproteins as vaccine candidates
journal, September 2015


Identification of novel immunogenic proteins of Neisseria gonorrhoeae by phage display
text, January 2019


Pathogenesis of Neisseria gonorrhoeae and the Host Defense in Ascending Infections of Human Fallopian Tube
journal, November 2018


Utility of Hybrid Transferrin Binding Protein Antigens for Protection Against Pathogenic Neisseria Species
journal, February 2019


Targeting Lipooligosaccharide (LOS) for a Gonococcal Vaccine
journal, February 2019


Estradiol-Treated Female Mice as Surrogate Hosts for Neisseria gonorrhoeae Genital Tract Infections
journal, January 2011


Experimental Gonococcal Infection in Male Volunteers: Cumulative Experience with Neisseria gonorrhoeae Strains FA1090 and MS11mkC
journal, January 2011

  • Hobbs, Marcia M.; Sparling, P. Frederick; Cohen, Myron S.
  • Frontiers in Microbiology, Vol. 2
  • DOI: 10.3389/fmicb.2011.00123