Share This Article:

A Peptide Containing T-Cell Epitopes of Chlamydia trachomatis Recombinant MOMP Induces Systemic and Mucosal Antibody Responses in Mice

Abstract Full-Text HTML XML Download Download as PDF (Size:1279KB) PP. 138-147
DOI: 10.4236/wjv.2011.14014    4,360 Downloads   8,629 Views   Citations

ABSTRACT

We reported that intranasal immunization of mice with recombinant major outer membrane protein (MOMP) of Chlamydia trachomatis genetically fused with modified cholera toxin elicited mucosal and systemic antibody responses, but with inefficient protective mechanisms for complete protection of mice against a homologous C. trachomtis challenged infection. To begin to identify specific immunogenic MOMP regions to pursue as vaccine candidates, herein we selected small gene fragments of the MOMP gene containing T-cell epitopes (278-370 aa) and generated a rMOMP peptide (rMOMP-278). rMOMP and rMOMP-278 proteins were cloned, expressed, and their purities and specificities confirmed by SDS-PAGE and Western blot, respectively. We tested the immunogenicity of rMOMP-278 as compared to the parent rMOMP in mice. Mice were immunized intramuscularly with purified rMOMP proteins; total- and isotype- (IgA, IgG1, IgG2a, and IgG2b) specific antibodies in sera and vaginal washes were measured by ELISA. Immunized mice developed antigen-specific total antibodies in a kinetic fashion, with responses being higher to rMOMP than rMOMP- 278. However, antigen-specific isotype antibodies were detected in the order of IgG2b > IgG2a > IgG1 for rMOMP- 278, indicating more of a mixed Th1/Th2 response. Contrastingly, antibody responses to rMOMP was more of a predominant Th2 response in the order of IgG1 > IgG2b > IgG2a. Our data are evidence to suggest that rMOMP-278 is immunogenic by its ability to evoke systemic and mucosal immune responses with a Th1 bias in mice, and therefore may be an attractive peptide alternative to full MOMP as a vaccine candidate against C. trachomatis genital tract infection.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

M. Taha, S. Singh, K. Hulett, S. Pillai, R. Agee and V. Dennis, "A Peptide Containing T-Cell Epitopes of Chlamydia trachomatis Recombinant MOMP Induces Systemic and Mucosal Antibody Responses in Mice," World Journal of Vaccines, Vol. 1 No. 4, 2011, pp. 138-147. doi: 10.4236/wjv.2011.14014.

References

[1] J. U. Igietseme, C. M. Black and H. D. Caldwell, “Chlamydia Vaccines: Strategies and Status,” Biology Drugs, Vol. 16, No. 1, 2002, pp. 19-35. doi:10.2165/00063030-200216010-00003
[2] F. O. Eko, Q. He, T. Brown, L. McMillan, G. O. Ifere, G. A. Ananaba, D. Lyn, W. Lubitz, K. L. Kellar, C. M. Black and J. U. Igietseme, “A Novel Recombinant Multisubunit Vaccine against Chlamydia,” Journal of Immunology, Vol. 173, 2004, pp. 3375-3382.
[3] R. C. Brunham and J. Rey-Ladino, “Immunology of Chlamydia Infection: Implications for a Chlamydia trachomatis Vaccine,” Nature Reviews Immunology, Vol. 5, No. 2, 2005, pp. 149-161. doi:10.1038/nri1551
[4] M. Tuffrey, I. Alexander, W. Conlan, C. Woods and M. Ward, “Hetrotypic Protection of Mice against Chlamydial Salpingitis and Colonization of the Lower Genital Tract with a Human Serovar F Isolate of C. trachomatis by Prior Immunization with Recombinant Serovar L1 Major Outer Membrane Protein,” Journal of General Microbiology, Vol. 138, 1992, pp. 1707-1715.
[5] B. E. Batteiger, R. G. Rank, P. M. Bavoil and L. S. F. Soderberg, “Partial Protection against Genital Reinfection by Immunization of Guinea-Pigs with Isolated Outer- Membrane Proteins of the Chlamydial Agent of Guinea- Pig Inclusion Conjunctivitis,” Journal of General Microbiology, Vol. 139, 1993, pp. 2965-2972.
[6] S. C. Knight, S. Iqball, C. Woods, A. Stagg, M. E. Ward and M. Tuffrey, “A Peptide of Chlamydia trachomatis Shown to be a Primary T-Cell Epitope in Vitro Induces Cell-Mediated Immunity in Vivo,” Immunology, Vol. 85, 1995, pp. 8-15.
[7] H. Su, M. Parnell and H. D. Caldwell, “Protective Efficacy of a Parenterally Administered MOMP-Derived Synthetic Oligopeptide Vaccine in a Murine Model of Chlamydia trachomatis Genital Tract Infection: Serum Neutralizing IgG Antibodies Do Not Protect against Genital Tract Infection,” Vaccine, Vol. 13, No. 11, 1995, pp. 1023-1032. doi:10.1016/0264-410X(95)00017-U
[8] S. R. Singh, K. Hulett, S. R. Pillai, V. A. Dennis, M. K. Oh and K. S. Gunn, “Mucosal Immunization with Recombinant MOMP Genetically Linked with Modified Cholera Toxin Confers Protection against Chlamydia trachomatis Infection,” Vaccine, Vol. 24, No. 8, 2006, pp. 1213-1224. doi:10.1016/j.vaccine.2005.08.097
[9] J. Hansen, K. T. Jensen, F. Follmann, E. M. Agger, M. Theisen and P. Andersen, “Liposome Delivery of Chlamydia muridarum Major Outer Membrane Protein Primes a Th1 Response That Protects against Genital Chlamydial Infection in a Mouse Model,” Journal of Infectious Diseases, Vol. 198, No. 5, 2008, pp. 758-767. doi:10.1086/590670
[10] C. Cheng, I. Bettahi, M. I. Cruz-Fisher, S. Pal, P. Jain, Z. Jia, J. Holmgren, A. M. Harandi and L. M. de la Mazaa, “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, Vol. 27, No. 44, 2009, pp. 6239-6246. doi:10.1016/j.vaccine.2009.07.108
[11] D. K. Hickey, F. E. Aldwell and K. W. Beagley, “Transcutaneous Immunization with a Novel Lipid-Based Adjuvant Protects against Chlamydia Genital and Respiratory Infections,” Vaccine, Vol. 27, No. 44, 2009, pp. 6217-6225. doi:10.1016/j.vaccine.2009.08.001
[12] K. Laszlo, W. M. Whitmire, D. D. Crane, N. Reveneau, J. H. Carlson, M. M. Goheen, E. M. Peterson, S. Pal, L. M. de la Maza and H. D. Caldwell, “Chlamydia trachomatis Native Major Outer Membrane Protein Induces Partial Protection in Non-Human Primates: Implication for a Trachoma Transmission Blocking Vaccine,” Journal of Immunology, Vol. 182, No. 12, 2009, pp. 8063-8070. doi:10.4049/jimmunol.0804375
[13] S. Guifeng, S. Pal, J. Weiland, E. M. Peterson and L. M. de la Maza, “Protection against an Intranasal Challenge by Vaccines Formulated with Native and Recombinant Preparations of the Chlamydia trachomatis Major Outer Membrane Protein,” Vaccine, Vol. 27, No. 36, 2009, pp. 5020-5025. doi:10.1016/j.vaccine.2009.05.008
[14] H. Lü, H. Wang, H. M. Zhao, L. Zhao, Q. Chen, M. Qi, J. Liu, H. Yu, X. P. Yu, X. Yang and W. M. Zhao, “Dendritic Cells (DCs) Transfected with a Recombinant Adenovirus Carrying Chlamydial Major Outer Membrane Protein Antigen Elicit Protective Immune Responses against Genital Tract Challenge Infection,” Biochemistry and Cell Biology, Vol. 88, No. 4, 2010, pp. 757-765. doi:10.1139/O10-011
[15] K. W. Beagley and P. Timms, “Chlamydia trachomatis Infection: Incidence, Health Costs and Prospects for Vaccine Development,” Journal of Reproductive Immunology, Vol. 48, No. 1, 2000, pp. 47-68. doi:10.1016/S0165-0378(00)00069-3
[16] F. O. Eko, W. Lubitz, L. McMillan, K. Ramey, T. Moore, G. A. Ananaba, D. Lyn, C. M. Black and J. U. Igietseme, “Recombinant Vibrio cholerae Ghosts as a Delivery Vehicle for Vaccinating against Chlamydia trachomatis,” Vaccine, Vol. 21, No. 15, 2003, pp. 1694-1703. doi:10.1016/S0264-410X(02)00677-1
[17] J. U. Igietseme and A. Murudin, “Induction of Protective Immunity against Chlamydia trachomatis Genital Infection by a Vaccine Based on Major Outer Membrane Protein-Lipophilic Imune Response-Stimulating Complexes,” Infection and Immunity, Vol. 66, 2000, pp. 4030-4035.
[18] S. Kim and R. Demars, “Epitope Clusters in the Major Outer Membrane Protein of Chlamydia trachomatis,” Current Opinion in Immunology, Vol. 13, No. 4, 2001, pp. 429-436. doi:10.1016/S0952-7915(00)00237-5
[19] L. Ortiz, M. Angevine, K. Suon-Kyeong, D. Watkins and R. Demars, “T-Cell Epitopes in Variable Segments of Chlamydia trachomatis Outer Membrane Protein Elicit Serovar-Specific Immune Responses in Infected Humans,” Infection and Immunity, Vol. 68, No. 3, 2000, pp. 1719- 1723. doi:10.1128/IAI.68.3.1719-1723.2000
[20] B. Toye, G. Zhong, R. Peeling and R. C. Brunham, “Immunologic Characterization of a Cloned Fragment Containing the Species-Specific Epitope from the Major Outer Membrane Protein of Chlamydia trachomatis,” Infection and Immunity, Vol. 58, 1990, pp. 3909-3913.
[21] G. Zhong and R. C. Brunham, “Immunoaccessible Peptide Sequences of the Major Outer Membrane Protein from Chlamydia trachomatis Serovar C,” Infection and Immunity, Vol. 58, 1990, pp. 3438-3441.
[22] W. P. Loomis and M. N. Starnbach, “T Cell Responses to Chlamydia trachomatis,” Current Opinion in Microbiology, Vol. 5, No. 1, 2002, pp. 87-91. doi:10.1016/S1369-5274(02)00291-6
[23] C. M. Farris, S. G. Morrison and R. P. Morrison, “CD4+ T Cells and Antibody Are Required for Optimal MOMP Vaccine Induced Immunity to Chlamydia muridarum Genital Infection,” Infection and Immunity, Vol. 78, No. 10, 2010, pp. 4374-4383. doi:10.1128/IAI.00622-10
[24] S. Pal, I. Theodor, E. Peterson and L. M. de la Maza, “Immunization with the Chlamydia trachomatis Mouse Pneumonitis Major Outer Membrane Protein Can Elicit a Protective Immune Response against a Genital Challenge,” Infection and Immunity, Vol. 69, No. 10, 2001, pp. 6240-6247. doi:10.1128/IAI.69.10.6240-6247.2001
[25] R. A. Hawkins, R. G. Rank and K. A. Kelly, “A Chlamydia trachomatis-Specific Th2 Clone Does Not Provide Protection against a Genital Infection and Displays Reduced Trafficking to the Infected Genital Mucosa,” Infection and Immunity, Vol. 70, No. 9, 2002, pp. 5132-5139. doi:10.1128/IAI.70.9.5132-5139.2002
[26] L. J. Berry, D. K. Hickey, K. A. Skelding, S. Bao, A. M. Rendina, P. M. Hansbro, C. M. Gockel, K. W. Beagley, “Transcutaneous Immunization with Combined Cholera Toxin and CpG Adjuvant Protects against Chlamydia muridarum Genital Tract Infection,” Infection and Immunity, Vol. 72, No. 2, 2004, pp. 1019-1028. doi:10.1128/IAI.72.2.1019-1028.2004
[27] D. K. Hickey, R. C. Jones, S. Bao, A. E. Blake, K. A. Skelding. L. J. Berry and K. W. Beagley, “Intranasal Immunization with C. muridarum Major Outer Membrane Protein (MOMP) and Cholera Toxin Elicits Local Production of Neutralising IgA in the Prostate,” Vaccine, Vol. 22, No. 31-32, 2004, pp. 4306-4315. doi:10.1016/j.vaccine.2004.04.021
[28] R. C. Brunham, C. C. Kuo, L. Cles and K. K. Holmes, “Correlation of Host Immune Response with Quantitative Recovery of Chlamydia trachomatis from the Human Endocervix,” Infection and Immunity, Vol. 39, 1983, pp. 1491-1494.
[29] K. A. Cunningham, A. J. Carey, L. Hafner, P. Timms and K. W. Beagley, “Chlamydia muridarum Major Outer Membrane Protein-Specific Antibodies Inhibit in Vitro Infection but Enhance Pathology in Vivo,” American Journal of Reproductive Immunology, Vol. 65, No. 2, 2010, pp. 118-126. doi:10.1111/j.1600-0897.2010.00894.x
[30] A. K. Murthy, P. J. Chambers, P. A. Meier, G. Zhong and B. P. Arulanandam, “Intranasal Vaccination with a Secreted Chlamydial Protein Enhances Resolution of Genital Chlamydia muridarum Infection, Protects against Oviduct Pathology, and Is Highly Dependent upon Endogenous Gamma Interferon Production,” Infection and Immunity, Vol. 75, No. 1, 2007, pp. 666-676. doi:10.1128/IAI.01280-06

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.