A majority of the Chlamydia trachomatis infections in women are symptomatic and thus, the only practical approach to prevent these disease is vaccinating the population at risk. In this proposal the investigators want to test the hypothesis that a vaccine consisting of the C. trachomatis major outer membrane protein (MOMP) will be able to induce protein in mice against a genital challenge with the C. trachomatis mouse pneumonitis (MoPn) biovar. To achieve this goal they want to utilize a MOMP preparation extracted from the native organisms that following purification has been """"""""folded"""""""". They will first test this vaccine candidate in BALB/c mice and subsequently will optimize the vaccine protocol in this strain of mice for the dose, route, and adjuvant formulation. The optimized vaccine preparation will then be tested for its ability to protect C3H and C57BL/6 mice and for inducing long term protection in BALB/c mice. In the immunized animals they will be assessing the parameters that are critical for protection using different approaches. They will first compare the immune responses in protected and control groups of mice, and will attempt to identify epitopes of the MOMP recognized by the B and T-cells. Another group of immunocompetent animals will be first immunized and will subsequently be treated with monoclonal antibodies to block CD4 and CD8 cells before they are challenged. In addition, knockout mice for the MHC class I (52m-/-) and MHC class II (B2m-/-) genes, and B (JHD), and T and B (rag-2), cell deficient animals will be immunized, challenged and mater to assess protection. Finally, they will use Stat4 and Stat6-deficient mice to characterize the role of Th1 and Th2 cells in protection. In conclusion, their goal is to establish an immunization protocol utilizing a purified and folded MOMP preparation that protects against a genital challenge, and to characterize the immune parameters that are critical for protection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI032248-10
Application #
6510640
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Quackenbush, Robert L
Project Start
1993-01-01
Project End
2003-09-29
Budget Start
2002-07-01
Budget End
2003-09-29
Support Year
10
Fiscal Year
2002
Total Cost
$363,558
Indirect Cost
Name
University of California Irvine
Department
Pathology
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Pal, Sukumar; Tatarenkova, Olga V; de la Maza, Luis M (2015) A vaccine formulated with the major outer membrane protein can protect C3H/HeN, a highly susceptible strain of mice, from a Chlamydia muridarum genital challenge. Immunology 146:432-43
Al-Kuhlani, Mufadhal; Rothschild, James; Rothchild, James et al. (2014) TRAIL-R1 is a negative regulator of pro-inflammatory responses and modulates long-term sequelae resulting from Chlamydia trachomatis infections in humans. PLoS One 9:e93939
Pal, Sukumar; de la Maza, Luis M (2013) Mechanism of T-cell mediated protection in newborn mice against a Chlamydia infection. Microbes Infect 15:607-14
Tifrea, Delia F; Sun, Guifeng; Pal, Sukumar et al. (2011) Amphipols stabilize the Chlamydia major outer membrane protein and enhance its protective ability as a vaccine. Vaccine 29:4623-31
Pal, Sukumar; Tatarenkova, Olga; de la Maza, Luis M (2010) Maternal immunity partially protects newborn mice against a Chlamydia trachomatis intranasal challenge. J Reprod Immunol 86:151-7
Pal, Sukumar; Sarcon, Annahita K; de la Maza, Luis M (2010) A new murine model for testing vaccines against genital Chlamydia trachomatis infections in males. Vaccine 28:7606-12
Kari, Laszlo; Whitmire, William M; Crane, Deborah D et al. (2009) Chlamydia trachomatis native major outer membrane protein induces partial protection in nonhuman primates: implication for a trachoma transmission-blocking vaccine. J Immunol 182:8063-70
Cai, Sumin; He, Feng; Samra, Hardeep S et al. (2009) Biophysical and stabilization studies of the Chlamydia trachomatis mouse pneumonitis major outer membrane protein. Mol Pharm 6:1553-61
Cheng, Chunmei; Bettahi, Ilham; Cruz-Fisher, Maria I et al. (2009) Induction of protective immunity by vaccination against Chlamydia trachomatis using the major outer membrane protein adjuvanted with CpG oligodeoxynucleotide coupled to the nontoxic B subunit of cholera toxin. Vaccine 27:6239-46
Sun, Guifeng; Pal, Sukumar; Weiland, Joseph et al. (2009) Protection against an intranasal challenge by vaccines formulated with native and recombinant preparations of the Chlamydia trachomatis major outer membrane protein. Vaccine 27:5020-5

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