Throughout the world Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen. In areas with poor sanitary conditions C. trachomatis causes trachoma, the most common cause of preventable blindness in the world. A majority of the genital C. trachomatis infections in women are asymptomatic. In addition, in symptomatic cases, unless therapy is implemented in a timely manner, long-term sequelae, including pelvic inflammatory disease, chronic abdominal pain, ectopic pregnancy and infertility, may develop. Thus, the only practical approach to prevent these diseases is vaccinating the population at risk. In this proposal we want to test the hypothesis that a vaccine formulated with the C. trachomatis major outer membrane protein (MOMP) can induce protection in female mice against a genital challenge. To achieve this goal we want to utilize a recombinant MOMP preparation of the mouse pneumonitis (MoPn) serovar expressed in Escherichia coli. We will first optimize the vaccination protocol in BALB/c mice for the route and adjuvant formulation so as to induce strong systemic and mucosal immune responses. Mice will be challenged in the genital tract at four weeks after the last immunization. Parameters of protection will include: histopathological changes in the genital tract, percentage of mice with positive vaginal cultures and severity and length of vaginal shedding. The optimized vaccine will then be tested for its ability to protect C3H/HeN and C57BL/6 mice. Protection against long-term sequelae will subsequently be evaluated by determining fertility rates and the number of embryos per pregnant animal. The vaccine will also be tested for its efficacy for inducing long-term protection. Specifically, vaccinated animals will be challenged in the genital tract at 60, 120 and 180 days after the last immunization. Finally, cross-protection will be established by vaccinating mice with recombinant MOMP preparations from MoPn and selected human serovars and determining their efficacy to protect against a challenge with the other human serovars. In conclusion, our goal is to establish a vaccination protocol utilizing a recombinant MOMP preparation to protect against a genital challenge with C. trachomatis. An efficacious vaccine against C. trachomatis will have a tremendous sanitary and economic impact throughout the world.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI067888-05
Application #
8028382
Study Section
Vaccines Against Microbial Diseases (VMD)
Program Officer
Hiltke, Thomas J
Project Start
2007-03-16
Project End
2013-02-28
Budget Start
2011-03-01
Budget End
2013-02-28
Support Year
5
Fiscal Year
2011
Total Cost
$366,564
Indirect Cost
Name
University of California Irvine
Department
Pathology
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Tifrea, Delia F; Barta, Michael L; Pal, Sukumar et al. (2016) Computational modeling of TC0583 as a putative component of the Chlamydia muridarum V-type ATP synthase complex and assessment of its protective capabilities as a vaccine antigen. Microbes Infect 18:245-53
Cheng, Chunmei; Jain, Pooja; Pal, Sukumar et al. (2014) Assessment of the role in protection and pathogenesis of the Chlamydia muridarum V-type ATP synthase subunit A (AtpA) (TC0582). Microbes Infect 16:123-33
Tifrea, Delia F; Pal, Sukumar; Popot, Jean-Luc et al. (2014) Increased immunoaccessibility of MOMP epitopes in a vaccine formulated with amphipols may account for the very robust protection elicited against a vaginal challenge with Chlamydia muridarum. J Immunol 192:5201-13
Patton, Dorothy L; Teng, Andy; Randall, Arlo et al. (2014) Whole genome identification of C. trachomatis immunodominant antigens after genital tract infections and effect of antibiotic treatment of pigtailed macaques. J Proteomics 108:99-109
Cheng, Chunmei; Pal, Sukumar; Tifrea, Delia et al. (2014) A vaccine formulated with a combination of TLR-2 and TLR-9 adjuvants and the recombinant major outer membrane protein elicits a robust immune response and significant protection against a Chlamydia muridarum challenge. Microbes Infect 16:244-52
Tifrea, Delia F; Ralli-Jain, Pooja; Pal, Sukumar et al. (2013) Vaccination with the recombinant major outer membrane protein elicits antibodies to the constant domains and induces cross-serovar protection against intranasal challenge with Chlamydia trachomatis. Infect Immun 81:1741-50
Feher, Victoria A; Randall, Arlo; Baldi, Pierre et al. (2013) A 3-dimensional trimeric *-barrel model for Chlamydia MOMP contains conserved and novel elements of Gram-negative bacterial porins. PLoS One 8:e68934
Carmichael, Jennifer R; Tifrea, Delia; Pal, Sukumar et al. (2013) Differences in infectivity and induction of infertility: a comparative study of Chlamydia trachomatis strains in the murine model. Microbes Infect 15:219-29
Massari, Paola; Toussi, Deana N; Tifrea, Delia F et al. (2013) Toll-like receptor 2-dependent activity of native major outer membrane protein proteosomes of Chlamydia trachomatis. Infect Immun 81:303-10
Tifrea, Delia F; Pal, Sukumar; Toussi, Deana N et al. (2013) Vaccination with major outer membrane protein proteosomes elicits protection in mice against a Chlamydia respiratory challenge. Microbes Infect 15:920-7

Showing the most recent 10 out of 22 publications