Protective immunity against Chlamydia trachomatis genital infection induced by a vaccine based on the major outer membrane multi-epitope human papillomavirus major capsid protein L1

• DOI: 10.1016/j.vaccine.2010.12.132
• Publication Date: 2011-02-15T15:14:12Z
• Authors: Wen Xu; Jianxiao Liu; Wenci Gong; Jun Chen; Shanli Zhu; Lifang Zhang
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Vaccines, Synthetic; Recombinant Fusion Proteins; Porins; Oncogene Proteins, Viral; Th1 Cells; Antibodies, Bacterial; Injections, Intramuscular; 3. Good health; Epitopes; Mice; 03 medical and health sciences; Bacterial Vaccines; Lymphogranuloma Venereum; Vaccines, DNA; Animals; Capsid Proteins; Female; T-Lymphocytes, Cytotoxic

The administration of an efficacious vaccine is the most effective long-term measure to control the genital tract infection caused by Chlamydia trachomatis (Ct) in humans. The current challenge for Ct vaccine development is to develop an effective delivery vehicle for induction of a high level of mucosal T and complementary B cell responses. We evaluated the immunogenicity and efficacy of a candidate vaccine comprising the major outer membrane protein (MOMP) multiepitope of Ct delivered with the human papillomavirus (HPV) major capsid protein L1 as a vehicle with adjuvant properties, in a murine model of chlamydial genital infection. A recombinant plasmid pcDNA3.1(+) containing mammalian codon-optimization HPV6b L1 gene and Ct MOMP multiepitope was constructed. The Ct MOMP multiepitope containing T- and B-cell epitope-rich peptides was inserted into C-terminal of HPV6b L1-coding sequence. The constructed plasmid after verified by enzyme restriction assay and DNA sequencing was transfected into COS-7 cells. Expression of the chimeric gene in COS-7 cells was confirmed by RT-PCR, Western blot analysis and immunofluorescence assay. Results revealed successful expression of the chimeric HPV6b L1/Ct MOMP multiepitope gene both at the mRNA and protein levels in transfected COS-7 cells. Intramuscular (IM) administration in mice was able to elicit not only antibodies against Ct MOMP, but also Th1 and cytotoxic T lymphocyte activity against the Ct MOMP epitopes. In addition, recipients of IM immunization of HPV6b L1/Ct MOMP multiepitope were highly resistant to infection. Altogether, the results suggested that IM delivery of HPV6b L1-MOMP multiepitope may be a suitable vaccine regimen potentially capable of inducing protective mucosal immunity against Ct infection.