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
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
DOI:
10.1016/j.vaccine.2010.12.132
Publication Date:
2011-02-15T15:14:12Z
AUTHORS (6)
ABSTRACT
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.
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