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Protection against genital tract Chlamydia trachomatis infection following intranasal immunization with a novel recombinant MOMP VS2/4 antigen
Örebro Life Science Center, School of Science and Technology, Örebro University, Örebro, Sweden; Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Department of Medical Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
Örebro University, School of Science and Technology. (Örebro Life Science Center)ORCID iD: 0000-0003-0018-8333
Department of Medical Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
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2016 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, p. 1078-1086Article in journal (Refereed) Published
Abstract [en]

The asymptomatic nature of most Chlamydia trachomatis infections and the lack of appropriate effects by current prevention and management call for vaccine development. We evaluated a recombinant subunit vaccine candidate based on the major outer membrane protein variable segments 2 and 4 (MOMP VS2/4). To achieve maximal immunogenicity and ease of production and purification, MOMP VS2/4 was constructed by using highly immunogenic sequences of MOMP only, thereby minimizing the presence of hydrophobic regions, and spacing the immunogenic epitopes with a flexible amino acid sequence. A purification tag was also added. The MOMP VS2/4 was given intranasally, with or without intravaginal boost, with cholera toxin (CT) adjuvant to C57BL/6 mice, which were screened for immunogenicity and protection against a live challenge infection with C. trachomatis serovar D. Bacterial shedding, cell-mediated responses, and antibody responses were monitored. Immunized mice exhibited significantly less bacterial shedding and were better protected against infertility as compared to unimmunized control mice. Immunizations stimulated both systemic and local specific antibody (IgG1, IgG2c, and IgA) responses, and primed T cells that produced interferon-c and interleukins 13 and 17 upon challenge with recall antigen. Thus, MOMP VS2/4, in combination with CT adjuvant, stimulated Th1, Th2, and Th17 effector cells, and generated protective immunity associated with less pathology. We regard MOMP VS2/4 as a promising candidate for further development into a mucosal chlamydial vaccine.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell, 2016. Vol. 124, p. 1078-1086
Keywords [en]
Chlamydia trachomatis, vaccine, major outer membrane protein, mice, antibody response, T cells
National Category
Immunology in the medical area Microbiology in the medical area
Research subject
Biochemistry; Immunology; Microbiology; Infectious Diseases
Identifiers
URN: urn:nbn:se:oru:diva-53554DOI: 10.1111/apm.12605ISI: 000388265700008PubMedID: 27859689Scopus ID: 2-s2.0-84995753108OAI: oai:DiVA.org:oru-53554DiVA, id: diva2:1047722
Projects
Utveckling av vacciner mot sexuellt överförbara sjukdomarMolecular farming
Funder
Olle Engkvists stiftelse
Note

Funding Agencies:

Sparbanksstiftelsen Nya

Örebro University's Faculty for Business, Science, and Technology

Foundation for Medical Research at Örebro University Hospital

Available from: 2016-11-18 Created: 2016-11-18 Last updated: 2024-01-16Bibliographically approved
In thesis
1. Implementation of strategies for management and prevention of sexually transmitted infections with focus on Neisseria gonorrhoeae and Chlamydia trachomatis
Open this publication in new window or tab >>Implementation of strategies for management and prevention of sexually transmitted infections with focus on Neisseria gonorrhoeae and Chlamydia trachomatis
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Sexually transmitted infections (STIs) are a public health issue of great importance worldwide, with effects on fertility and reproduction. Chlamydia trachomatis and Neisseria gonorrhoeae, causative agents of chlamydia and gonorrhoea, respectively, are the most common bacterial STIs with an estimated 127 million new global cases of chlamydia and 87 million new gonorrhoea cases. The continued emergence of antimicrobial resistance (AMR) in N. gonorrhoeae may in the future lead to an untreatable infection. Prevention of these infections and controlling the development of AMR rely on several strategies developed by the World Health Organization (WHO). This thesis aimed to implement several of these strategies, including supporting vaccine development for C. trachomatis and N. gonorrhoeae, evaluating molecular methods for detecting N. gonorrhoeae, predicting AMR and supporting surveillance of the spread and prevalence of AMR in N. gonorrhoeae. The present studies on a C. trachomatis recombinant vaccine antigen and the investigation of similarities of N. gonorrhoeae antigen amino acid sequences to the antigens included in the meningococcal vaccine 4CMenB contributed to the field of vaccine development for STIs. The assay SpeeDx ResistancePlus® GC performed well in detecting N. gonorrhoeae and predicting ciprofloxacin resistance and could be used in AMR surveillance and individualised treatment. In 2016, the first national genomic surveillance of all N. gonorrhoeae isolates in Sweden was performed. This national surveillance study included whole-genome sequencing combined with phenotypic AMR and epidemiological data, which provides valuable information on circulating strains, epidemiology and phylogeny. Greater knowledge of gonorrhoea and gonococcal AMR epidemiology could inform decisions on guidelines and prevention. It is essential to continue to implement WHO strategies at the national and global levels to prevent and control chlamydia and gonorrhoea infections.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2022. p. 104
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 267
Keywords
Neisseria gonorrhoeae, epidemiology, whole-genome sequencing, antimicrobial resistance (AMR), Chlamydia trachomatis, vaccine, strategies, management and prevention
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:oru:diva-98526 (URN)9789175294407 (ISBN)
Public defence
2022-06-17, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2022-04-11 Created: 2022-04-11 Last updated: 2022-06-16Bibliographically approved

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Hadad, RonzaKalbina, IrinaUnemo, MagnusStrid, ÅkeAndersson, Sören

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