PubMLST for Antigen Allele Mining to Inform Development of Gonorrhea Protein-Based Vaccines.

Benjamin I Baarda,Robert A Nicholas,Aleksandra E Sikora,Ryszard A Zielke

doi:10.3389/fmicb.2018.02971

Abstract

Neisseria gonorrhoeae (Ng) is a human-specific pathogen and the etiological agent of gonorrhea, a sexually transmitted infection with a significant global health burden. While often asymptomatic, untreated gonorrhea can lead to pelvic inflammatory disease, ectopic pregnancy, infertility, and increased transmission/acquisition of HIV. A protective gonorrhea vaccine may be the only way to control disease transmission in the future due to the inexorable development of antibiotic resistance. Subunit antigens are proven candidates for vaccine development due to their safety, cost-effectiveness, and rapid preparation. To inform protein-based gonorrhea vaccine design by including different antigen variants, herein we present bioinformatics mining of alleles and single nucleotide/amino acid polymorphisms using DNA/protein sequences of all Ng isolates deposited into the PubMLST database and MtrE and BamA as model antigens. We also present phylogenetic analyses that can be performed using sequence data to gain insights into the evolutionary relationships between the polymorphisms found among the population of isolates using a convenient tool: Molecular Evolutionary Genetics Analysis (MEGA) software. Finally, we perform antigen polymorphism mapping onto the MtrE and BamA structures. This methodology can be applied for rational vaccine design to increase vaccine coverage and cross-protection by heteroligand presentation achieved via inclusion of diverse antigen variants and is relevant to over 100 different species and genera deposited into the PubMLST family of databases.

Highlights

Gonorrhea is a sexually transmitted infection caused by Neisseria gonorrhoeae (Ng), a humanspecific pathogen that infects over 78 million people worldwide (Newman et al, 2015)
In support of this finding, immunization of mice with the similar 4CMenB vaccine significantly increased Ng clearance in the mouse model of gonorrhea (P < 0.0001), and sera from 4CMenB-vaccinated mice cross-reacted with several proteins of the Ng outer membrane, including MtrE, BamA, Opa, and PilQ, suggesting that these are the cross-protective proteins (Connolly et al, 2018)
To inform protein-based gonorrhea vaccine design by including the most prevalent alleles of the target antigens to provide broad protection, we present bioinformatics mining of all Ng isolates deposited into the PubMLST database1 to identify alleles and single nucleotide/amino acid polymorphisms of the model antigens MtrE and BamA

Summary

Introduction

Gonorrhea is a sexually transmitted infection caused by Neisseria gonorrhoeae (Ng), a humanspecific pathogen that infects over 78 million people worldwide (Newman et al, 2015). To inform protein-based gonorrhea vaccine design by including the most prevalent alleles of the target antigens to provide broad protection, we present bioinformatics mining of all Ng isolates deposited into the PubMLST database1 to identify alleles and single nucleotide/amino acid polymorphisms of the model antigens MtrE and BamA.

Results

Conclusion