UMMS Affiliation

Division of Infectious Diseases and Immunology, Department of Medicine

Publication Date

2019-02-27

Document Type

Article

Disciplines

Bacteria | Bacterial Infections and Mycoses | Bacteriology | Hemic and Immune Systems | Immunity | Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Therapeutics

Abstract

The increasing incidence of gonorrhea worldwide and the global spread of multidrug-resistant strains of Neisseria gonorrhoeae, constitute a public health emergency. With dwindling antibiotic treatment options, there is an urgent need to develop safe and effective vaccines. Gonococcal lipooligosaccharides (LOSs) are potential vaccine candidates because they are densely represented on the bacterial surface and are readily accessible as targets of adaptive immunity. Less well-understood is whether LOSs evoke protective immune responses. Although gonococcal LOS-derived oligosaccharides (OSs) are major immune targets, often they undergo phase variation, a feature that seemingly makes LOS less desirable as a vaccine candidate. However, the identification of a gonococcal LOS-derived OS epitope, called 2C7, that is: (i) a broadly expressed gonococcal antigenic target in human infection; (ii) a virulence determinant, that is maintained by the gonococcus and (iii) a critical requirement for gonococcal colonization in the experimental setting, circumvents its limitation as a potential vaccine candidate imposed by phase variation. Difficulties in purifying structurally intact OSs from LOSs led to "conversion" of the 2C7 epitope into a peptide mimic that elicited cross-reactive IgG anti-OS antibodies that also possess complement-dependent bactericidal activity against gonococci. Mice immunized with the 2C7 peptide mimic clear vaginal colonization more rapidly and reduce gonococcal burdens. 2C7 vaccine satisfies criteria that are desirable in a gonococcal vaccine candidate: broad representation of the antigenic target, service as a virulence determinant that is also critical for organism survival in vivo and elicitation of broadly cross-reactive IgG bactericidal antibodies when used as an immunogen.

Keywords

Lipooligosaccharide, N. gonorrhoeae, complement, peptide mimic, vaccine

Rights and Permissions

Copyright © 2019 Gulati, Shaughnessy, Ram and Rice. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

DOI of Published Version

10.3389/fimmu.2019.00321

Source

Front Immunol. 2019 Feb 27;10:321. doi: 10.3389/fimmu.2019.00321. eCollection 2019. Link to article on publisher's site

Journal/Book/Conference Title

Frontiers in immunology

Related Resources

Link to Article in PubMed

PubMed ID

30873172

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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