Hepatitis B virus core antigen as a carrier for Chlamydia trachomatis MOMP multi-epitope peptide enhances protection against genital chlamydial infection

Abstract

Chlamydia trachomatis (Ct) is the leading cause of sexually transmitted diseases worldwide. There is no safe and effective vaccine to control the spread of Ct. In development of Ct vaccine, selection of appropriate candidate antigens and an effective delivery system may be the main challenges. Multi-epitope of major outer membrane protein (MOMPm) is the most suitable candidate for a Ct vaccine, while hepatitis B virus core antigen (HBcAg) has unique advantages as vaccine delivery system. Therefore, in this study, we evaluated the immunogenicity and protective immune response of a novel candidate vaccine in a murine model of chlamydial genital infection. This candidate vaccine comprises MOMPm peptide delivered with HBcAg. Our results of Ct-specific serum IgG and secretory IgA assay, cytokine assay, and cytotoxic T-lymphocyte assay revealed that immunogenicity of the candidate vaccine was much better than that of the corresponding synthetic MOMPm peptide. Furthermore, the protective effect of the candidate vaccine was also shown much better than that of the synthetic peptide by calculating the isolation of Chlamydia from vaginal swabs and histopathological analysis. Taken together, our results indicate that HBcAg carrying Ct MOMPm could be an effective immune prophylactic for chlamydial infection.

Targeted Protein-Specific Multi-Epitope-Based Vaccine Designing against Human Cytomegalovirus by Using Immunoinformatics Approaches

“…These adjuvants linked immune epitope-based vaccine constructs are capable of expressing the sequence of the most important pathogen protein antigens in DNA plasmids. Advanced strategies involving virus-like particles (VLPs) [ 61 , 62 ] and nanoparticles [ 63 , 64 ] have been used as vehicles for delivering multi-epitope vaccines. Upon host-delivery of the subunit peptide vaccines, a conformation-dependent way is followed by antibodies in targeting these antigens [ 65 ].…”

Seventy Years of Chlamydia Vaccine Research – Limitations of the Past and Directions for the Future

“…However, humoral immune responses in plasma anti-MOMP IgG were detected along with trace levels of mucosal anti-MOMP IgA. This disappointing result was repeated in six additional protein-based vaccine trials over the next 20 years, with the only improvement being that the increases in plasma IgG responses had Chlamydia neutralizing effects (Su and Caldwell, 1993; Knight et al, 1995; Igietseme and Murdin, 2000; Shaw et al, 2002; Zheng et al, 2006; Jiang et al, 2015). None of these seven trials used an adjuvant to stimulate immune responses during vaccination, generating a clear indication that an adjuvant-based vaccine would be required for a successful immunological response within a protein-based vaccine.…”

Multi-epitope vaccines: a promising strategy against tumors and viral infections

“…12,13 In our laboratory, we always use immunoinformatic tools to predict and screen the immunogenic T-and B-cell epitopes of the target antigens, then design peptides rich in epitopes or overlapping epitopes. 7,8,11,14,15 For the prediction of B-cell epitopes, multiple alignments of the target antigen are initially carried out using software from the European Bioinformatics Institute website (http://www.ebi.ac.uk/Tools/ clustalw2). Then, the structure, hydrophilicity and flexibility, and transmembrane domains of the target antigen are predicted and analyzed by methods including GOR, 16 Hoop and Woods 17 and artificial neural network (http:// strucbio.biologie.uni-konstanz.de).…”

“…The successful immunotherapy of a multi-epitope vaccine is also associated with an effective vaccine delivery system. At present, both virus-like particles (VLPs) 7,8,14 and nanoparticles 18,19 have been used as vehicles for delivering multi-epitope vaccines. We have used two types of VLPs: hepatitis B core antigen (HBcAg)-VLPs and hepatitis B surface antigen (HBsAg)-VLPs.…”

“…Our data have shown that either HBcAg or HBsAg-VLPs multi-epitope vaccines strongly elicit specifically humoral and cellular immune responses and generate vigorous immune responses of the individual epitopes carried by the multi-epitope vaccine. 7,8,14 In summary, multi-epitope vaccines can be considered as a promising strategy against tumors and viral infections. Immunoinformatics methods can help to predict and screen appropriate epitopes for designing an efficacious multi-epitope vaccine.…”