Protection against genital tract Chlamydia trachomatis infection following intranasal immunization with a novel recombinant MOMP VS2/4 antigenShow others and affiliations
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
2016-11-182016-11-182024-01-16Bibliographically approved
In thesis