CT043, a Protective Antigen That Induces a CD4+ Th1 Response during Chlamydia trachomatis Infection in Mice and Humans

ABSTRACT Despite several decades of intensive studies, no vaccines against Chlamydia trachomatis, an intracellular pathogen causing serious ocular and urogenital diseases, are available yet. Infection-induced immunity in both animal models and humans strongly supports the notion that for a vaccine to be effective a strong CD4+ Th1 immune response should be induced. In the course of our vaccine screening program based on the selection of chlamydial proteins eliciting cell-mediated immunity, we have found that CT043, a protein annotated as hypothetical, induces CD4+ Th1 cells both in chlamydia-infected mice and in human patients with diagnosed C. trachomatis genital infection. DNA priming/protein boost immunization with CT043 results in a 2.6-log inclusion-forming unit reduction in the murine lung infection model. Sequence analysis of CT043 from C. trachomatis human isolates belonging to the most representative genital serovars revealed a high degree of conservation, suggesting that this antigen could provide cross-serotype protection. Therefore, CT043 is a promising vaccine candidate against C. trachomatis infection.

[1]  C. Créminon,et al.  Generating antibodies against the native form of the human prion protein (hPrP) in wild-type animals: a comparison between DNA and protein immunizations. , 2009, Journal of immunological methods.

[2]  P. Andersen,et al.  Antigenic profiling of a Chlamydia trachomatis gene-expression library. , 2008, The Journal of infectious diseases.

[3]  L. Hafner,et al.  Vaccines for Chlamydia infections of the female genital tract. , 2008, Future microbiology.

[4]  P. Højrup,et al.  Identification of CT521 as a frequent target of Th1 cells in patients with urogenital Chlamydia trachomatis infection. , 2006, The Journal of infectious diseases.

[5]  J. Mascola,et al.  Immunization of rhesus macaques with a polyvalent DNA prime/protein boost human immunodeficiency virus type 1 vaccine elicits protective antibody response against simian human immunodeficiency virus of R5 phenotype. , 2006, Virology.

[6]  Shixia Wang,et al.  Preclinical evaluation of cellular immune responses elicited by a polyvalent DNA prime/protein boost HIV-1 vaccine. , 2006, Virology.

[7]  G. Bensi,et al.  Characterization and identification of vaccine candidate proteins through analysis of the group A Streptococcus surface proteome , 2006, Nature Biotechnology.

[8]  S. Morrison,et al.  A Predominant Role for Antibody in Acquired Immunity to Chlamydial Genital Tract Reinfection1 , 2005, The Journal of Immunology.

[9]  R. Brunham,et al.  Immunology of Chlamydia infection: implications for a Chlamydia trachomatis vaccine , 2005, Nature Reviews Immunology.

[10]  G. Grandi,et al.  Identification of new potential vaccine candidates against Chlamydia pneumoniae by multiple screenings. , 2005, Vaccine.

[11]  P. Wyrick,et al.  Pre-exposure of infected human endometrial epithelial cells to penicillin in vitro renders Chlamydia trachomatis refractory to azithromycin. , 2004, The Journal of antimicrobial chemotherapy.

[12]  J. Igietseme Towards a Chlamydia vaccine , 2004 .

[13]  E. Peterson,et al.  Vaccines for Chlamydia trachomatis infections. , 2002, Current opinion in investigational drugs.

[14]  F. Eko,et al.  Fc receptor regulation of protective immunity against Chlamydia trachomatis , 2002, Immunology.

[15]  R. Nogarotto,et al.  Genomic Approach for Analysis of Surface Proteins in Chlamydia pneumoniae , 2002, Infection and Immunity.

[16]  E. Peterson,et al.  Immunization with the Chlamydia trachomatis Mouse Pneumonitis Major Outer Membrane Protein Can Elicit a Protective Immune Response against a Genital Challenge , 2001, Infection and Immunity.

[17]  F. Portaels,et al.  Protective Efficacy of a DNA Vaccine Encoding Antigen 85A from Mycobacterium bovis BCG against Buruli Ulcer , 2001, Infection and Immunity.

[18]  S. K. Kim,et al.  Epitope clusters in the major outer membrane protein of Chlamydia trachomatis. , 2001, Current opinion in immunology.

[19]  E. Signori,et al.  Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase – increased expression with reduced muscle damage , 2001, Gene Therapy.

[20]  B. Polgár,et al.  Progesterone as an immunomodulatory molecule. , 2001, International immunopharmacology.

[21]  T. Hatch,et al.  Characterization of Outer Membrane Proteins in Chlamydia trachomatis LGV Serovar L2 , 2001, Journal of bacteriology.

[22]  J. Reimann,et al.  Revealing the Potential of DNA-Based Vaccination: Lessons Learned from the Hepatitis B Virus Surface Antigen , 2001, Biological chemistry.

[23]  A. Hudson,et al.  Persistence of Chlamydia trachomatis Is Induced by Ciprofloxacin and Ofloxacin In Vitro , 2000, Antimicrobial Agents and Chemotherapy.

[24]  R. Rappuoli,et al.  Modulation of Innate and Acquired Immune Responses by Escherichia coli Heat-Labile Toxin: Distinct Pro- and Anti-Inflammatory Effects of the Nontoxic AB Complex and the Enzyme Activity1 , 2000, The Journal of Immunology.

[25]  A. Hill,et al.  Vaccines against intracellular infections requiring cellular immunity , 2000, Nature.

[26]  R. Brunham,et al.  Priming with Chlamydia trachomatis Major Outer Membrane Protein (MOMP) DNA followed by MOMP ISCOM Boosting Enhances Protection and Is Associated with Increased Immunoglobulin A and Th1 Cellular Immune Responses , 2000, Infection and Immunity.

[27]  J. Ulmer,et al.  Increased DNA Vaccine Delivery and Immunogenicity by Electroporation In Vivo , 2000, The Journal of Immunology.

[28]  K. Workowski,et al.  Multiple drug-resistant Chlamydia trachomatis associated with clinical treatment failure. , 2000, The Journal of infectious diseases.

[29]  T. Bjørge,et al.  Chlamydia trachomatis infection as a risk factor for invasive cervical cancer , 2000, International journal of cancer.

[30]  W Chiu,et al.  EMAN: semiautomated software for high-resolution single-particle reconstructions. , 1999, Journal of structural biology.

[31]  B. Finlay,et al.  Enteropathogenic Escherichia coli: a pathogen that inserts its own receptor into host cells , 1999, Cellular and Molecular Life Sciences CMLS.

[32]  R. Stephens Chlamydia: Intracellular Biology, Pathogenesis, And Immunity , 1999 .

[33]  H. Davis,et al.  CpG DNA is a potent enhancer of systemic and mucosal immune responses against hepatitis B surface antigen with intranasal administration to mice. , 1998, Journal of immunology.

[34]  A. Thomas,et al.  Multi‐plasmid DNA vaccination avoids antigenic competition and enhances immunogenicity of a poorly immunogenic plasmid , 1998, European journal of immunology.

[35]  W. V. Van Voorhis,et al.  Repeated Chlamydia trachomatis infection of Macaca nemestrina fallopian tubes produces a Th1-like cytokine response associated with fibrosis and scarring , 1997, Infection and immunity.

[36]  W. V. Van Voorhis,et al.  Analysis of lymphocyte phenotype and cytokine activity in the inflammatory infiltrates of the upper genital tract of female macaques infected with Chlamydia trachomatis. , 1996, The Journal of infectious diseases.

[37]  H. Caldwell,et al.  CD4+ T cells play a significant role in adoptive immunity to Chlamydia trachomatis infection of the mouse genital tract , 1995, Infection and immunity.

[38]  M. Ward The immunobiology and immunopathology of chlamydial infections , 1995, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[39]  J. Walboomers,et al.  Direct detection and genotyping of Chlamydia trachomatis in cervical scrapes by using polymerase chain reaction and restriction fragment length polymorphism analysis , 1993, Journal of clinical microbiology.

[40]  D. Tang,et al.  Genetic immunization is a simple method for eliciting an immune response , 1992, Nature.

[41]  P. Piot,et al.  Cofactors in male-female sexual transmission of human immunodeficiency virus type 1. , 1991, The Journal of infectious diseases.

[42]  E. Coligan Current protocols in immunology , 1991 .

[43]  D. Taylor-Robinson,et al.  Salpingitis in mice induced by human strains of Chlamydia trachomatis. , 1986, British journal of experimental pathology.

[44]  R. Rank,et al.  Chronic chlamydial genital infection in congenitally athymic nude mice , 1985, Infection and immunity.

[45]  H. Caldwell,et al.  Purification and partial characterization of the major outer membrane protein of Chlamydia trachomatis , 1981, Infection and immunity.