Proteomics, Bioinformatics and Structure-Function Antigen Mining For Gonorrhea Vaccines.

Benjamin I Baarda,Aleksandra E Sikora,Fabian G Martinez

doi:10.3389/fimmu.2018.02793

Abstract

Expanding efforts to develop preventive gonorrhea vaccines is critical because of the serious health consequences combined with the prevalence and the dire possibility of untreatable gonorrhea. Reverse vaccinology, which includes genome and proteome mining, has proven successful in the discovery of vaccine candidates against many pathogenic bacteria. Here, we describe proteomic applications including comprehensive, quantitative proteomic platforms and immunoproteomics coupled with broad-ranging bioinformatics that have been applied for antigen mining to develop gonorrhea vaccine(s). We further focus on outlining the vaccine candidate decision tree, describe the structure-function of novel proteome-derived antigens as well as ways to gain insights into their roles in the cell envelope, and underscore new lessons learned about the fascinating biology of Neisseria gonorrhoeae.

Highlights

Worldwide, over 78 million people are estimated to acquire the sexually transmitted infection gonorrhea every year [1]
It is possible that the antigens eventually formulated into a successful gonorrhea vaccine will not generate neutralizing antibodies, but evidence suggests antibodies that block protein function to some extent are elicited in the majority of immune responses effective at protecting against bacterial pathogens
Proteomics-driven antigen discovery should be paired with comprehensive bioinformatic analyses to enable more informed decisions for rational development of subunit vaccines and facilitate the inclusion of highly conserved surface-exposed proteins with important functions

Summary

INTRODUCTION

Over 78 million people are estimated to acquire the sexually transmitted infection gonorrhea every year [1]. 98% of isolates in the database possessed a single sliC allele [99], indicating that this protein is highly conserved and its inclusion in a vaccine could provide broad protection without the need for multiple antigenic variants Another analysis made possible by the information present in the PubMLST database is to map polymorphisms to available structural data (Figure 2). It is possible that the antigens eventually formulated into a successful gonorrhea vaccine will not generate neutralizing antibodies, but evidence suggests antibodies that block protein function to some extent are elicited in the majority of immune responses effective at protecting against bacterial pathogens. Evaluation of subunit vaccines beyond their ability to accelerate clearance and protect against subsequent infection will include quantification of antigen-specific IgG and IgA antibody titers in serum and vaginal mucosal secretions, evaluation of antibodies’ bactericidal and opsonophagocytic activities, and examination of the cellular immune response. The structural studies we have discussed here give context to the function of our proteome-derived vaccine candidates, and give insights into critical, surface-exposed portions of the proteins that can be targeted through structural vaccinology approaches

CONCLUDING REMARKS

Findings

Methods and Results