A DNA Fusion Vaccine Induces Bactericidal Antibodies to a Peptide Epitope from the PorA Porin of Neisseria meningitidis

Abstract

An experimental DNA plasmid vaccine was developed based on a well-characterized and protective peptide epitope derived from a bacterial porin protein. For this study, we used the P1.16b serosubtype epitope, located in variable region (VR)2 in loop 4 of the PorA outer membrane (OM) porin from Neisseria meningitidis serogroup B strain MC58. A plasmid that encoded the entire loop (pPorAloop4) was prepared, as well as a fusion plasmid that encoded the loop in tandem with the fragment C (FrC) immunostimulatory sequence from tetanus toxin (pPorAloop4-FrC). The constructs were used for intramuscular immunization without exogenous adjuvant. Murine antisera raised to the pPorAloop4-FrC DNA fusion plasmid reacted significantly with OMs in enzyme-linked immunosorbent assay and with whole bacteria by immunofluorescence, whereas antisera raised to the pPorAloop4 DNA plasmid and to control plasmid showed little or no reactivity. Significantly, only the pPorALoop4-FrC plasmid induced bactericidal antibodies, demonstrating that the intrinsic immunostimulatory sequence was essential for inducing a protective immune response. The antibodies raised to the P1.16b pPorALoop4-FrC plasmid were serosubtype specific, showing no significant immunofluorescence reactivity or bactericidal activity against other PorA variants. These data provide proof of principle for a DNA fusion plasmid strategy as a novel approach to preparing vaccines based on defined, protective epitopes.

Evaluation of a Novel Chimeric B Cell Epitope-Based Vaccine against Mastitis Induced by Either Streptococcus agalactiae or Staphylococcus aureus in Mice

“…Problems have been due to the high number of mastitis pathogens and their heterogeneity, high production costs, and poor availability or poor efficiency (25). Immune boosting with epitope-based vaccines has been shown to be successful for various infectious diseases, such as Salmonella enterica serovar Enteritidis infection (32), Neisseria meningitidis infection (35), and tuberculosis (7). Moreover, the epitope vaccine can be easily delivered and is capable of stimulating effective immune responses while avoiding potentially hazardous and undesirable side effects (34).…”

A Novel Recombinant Virus-Like Particles Displaying B and T Cell Epitopes of Japanese Encephalitis Virus Offers Protective Immunity in Mice and Guinea Pigs

“…Additionally, this stability reduces the cost of vaccines by allowing a longer shelf life and reduces energy costs associated with cold-storage [ 37 ]. This approach has been successfully used in various infectious diseases, such as human papillomavirus (HPV) [ 38 ], hepatitis B virus [ 39 ], and Neisseria meningitides infection [ 40 ]. Therefore, in this study, a novel VLP vaccine displaying B and T cell epitopes of JEV was proposed as a possible candidate vaccine with a significant capacity to induce protection against a JEV challenge in mice, with some protective immunity against PPV challenge in guinea pigs.…”

In silico experiment with an-antigen-toll like receptor-5 agonist fusion construct for immunogenic application to Helicobacter pylori

“…Recently, the focus of vaccine development has shifted to multi-epitope vaccines as a new strategy to control certain severe and chronic infectious diseases, such as AIDS,[42] meningitis,[43] malaria,[44] tuberculosis,[31] and hemorrhagic diarrhea. [45] Potential advantages of epitope-based vaccines could result in this type of vaccine being an effective strategy to control H. pylori .…”