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Structural and Immunological Characterization of Novel Recombinant MOMP-Based Chlamydial Antigens

Chlamydia is the most common cause of bacterial sexually transmitted infections worldwide. While infections resolve with antibiotic treatment, this is often neglected in women due to frequent asymptomatic infections, leading to disease progression and severe sequelae (pelvic inflammatory disease, ec...

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Detalles Bibliográficos
Autores principales: Madico, Guillermo, Gursky, Olga, Fairman, Jeff, Massari, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874643/
https://www.ncbi.nlm.nih.gov/pubmed/29295593
http://dx.doi.org/10.3390/vaccines6010002
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author Madico, Guillermo
Gursky, Olga
Fairman, Jeff
Massari, Paola
author_facet Madico, Guillermo
Gursky, Olga
Fairman, Jeff
Massari, Paola
author_sort Madico, Guillermo
collection PubMed
description Chlamydia is the most common cause of bacterial sexually transmitted infections worldwide. While infections resolve with antibiotic treatment, this is often neglected in women due to frequent asymptomatic infections, leading to disease progression and severe sequelae (pelvic inflammatory disease, ectopic pregnancy, infertility). Development of a vaccine against Chlamydia is crucial. Whole organism-based vaccines have short-lived activity, serovar/subgroup-specific immunity and can cause adverse reactions in vaccinated subjects. The Chlamydia major outer membrane protein (MOMP) is a prime candidate for a subunit vaccine. MOMP contains four regions of sequence variability (variable domains, VDs) with B-cell and T-cell epitopes that elicit protective immunity. However, barriers for developing a MOMP-based vaccine include solubility, yield and refolding. We have engineered novel recombinant antigens in which the VDs are expressed into a carrier protein structurally similar to MOMP and suitable for recombinant expression at a high yield in a correctly folded and detergent-free form. Using a carrier such as the PorB porin from the human commensal organism N. lactamica, we show that PorB/VD chimeric proteins are immunogenic, antigenic and cross-reactive with MOMP. VDs are unique for each serovar but if combined in a single vaccine, a broad coverage against the major Chlamydia serovars can be ensured.
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spelling pubmed-58746432018-04-02 Structural and Immunological Characterization of Novel Recombinant MOMP-Based Chlamydial Antigens Madico, Guillermo Gursky, Olga Fairman, Jeff Massari, Paola Vaccines (Basel) Article Chlamydia is the most common cause of bacterial sexually transmitted infections worldwide. While infections resolve with antibiotic treatment, this is often neglected in women due to frequent asymptomatic infections, leading to disease progression and severe sequelae (pelvic inflammatory disease, ectopic pregnancy, infertility). Development of a vaccine against Chlamydia is crucial. Whole organism-based vaccines have short-lived activity, serovar/subgroup-specific immunity and can cause adverse reactions in vaccinated subjects. The Chlamydia major outer membrane protein (MOMP) is a prime candidate for a subunit vaccine. MOMP contains four regions of sequence variability (variable domains, VDs) with B-cell and T-cell epitopes that elicit protective immunity. However, barriers for developing a MOMP-based vaccine include solubility, yield and refolding. We have engineered novel recombinant antigens in which the VDs are expressed into a carrier protein structurally similar to MOMP and suitable for recombinant expression at a high yield in a correctly folded and detergent-free form. Using a carrier such as the PorB porin from the human commensal organism N. lactamica, we show that PorB/VD chimeric proteins are immunogenic, antigenic and cross-reactive with MOMP. VDs are unique for each serovar but if combined in a single vaccine, a broad coverage against the major Chlamydia serovars can be ensured. MDPI 2017-12-25 /pmc/articles/PMC5874643/ /pubmed/29295593 http://dx.doi.org/10.3390/vaccines6010002 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Madico, Guillermo
Gursky, Olga
Fairman, Jeff
Massari, Paola
Structural and Immunological Characterization of Novel Recombinant MOMP-Based Chlamydial Antigens
title Structural and Immunological Characterization of Novel Recombinant MOMP-Based Chlamydial Antigens
title_full Structural and Immunological Characterization of Novel Recombinant MOMP-Based Chlamydial Antigens
title_fullStr Structural and Immunological Characterization of Novel Recombinant MOMP-Based Chlamydial Antigens
title_full_unstemmed Structural and Immunological Characterization of Novel Recombinant MOMP-Based Chlamydial Antigens
title_short Structural and Immunological Characterization of Novel Recombinant MOMP-Based Chlamydial Antigens
title_sort structural and immunological characterization of novel recombinant momp-based chlamydial antigens
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874643/
https://www.ncbi.nlm.nih.gov/pubmed/29295593
http://dx.doi.org/10.3390/vaccines6010002
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