A DNA fusion vaccine induces bactericidal antibodies to a peptide epitope from the PorA porin of Neisseria meningitidis
A DNA fusion vaccine induces bactericidal antibodies to a peptide epitope from the PorA porin of Neisseria meningitidis
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.
variable region, region, variant, malaria, synthetic peptides, repair, capsular polysaccharide, b meningococci, dna, genetic immunization, immune-response, fusion, immune response, peptide, vaccine, time, infection, outer-membrane protein, protein, protective antibodies, induction
334-338
Zhu, Delin
49eeb78f-f607-4079-80b3-45574dc41fa5
Williams, Jeannette N.
14e675d9-8b05-4650-b01a-c52e73e903f4
Rice, Jason
d58d4fcd-8dc0-4599-bf96-62323d579227
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Heckels, John E.
fcfcfafe-5ca8-4728-9c5e-cb67f9af7e31
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
January 2008
Zhu, Delin
49eeb78f-f607-4079-80b3-45574dc41fa5
Williams, Jeannette N.
14e675d9-8b05-4650-b01a-c52e73e903f4
Rice, Jason
d58d4fcd-8dc0-4599-bf96-62323d579227
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Heckels, John E.
fcfcfafe-5ca8-4728-9c5e-cb67f9af7e31
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Zhu, Delin, Williams, Jeannette N., Rice, Jason, Stevenson, Freda K., Heckels, John E. and Christodoulides, Myron
(2008)
A DNA fusion vaccine induces bactericidal antibodies to a peptide epitope from the PorA porin of Neisseria meningitidis.
Infection and Immunity, 76 (1), .
(doi:10.1128/IAI.00943-07).
(PMID:17967859)
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.
This record has no associated files available for download.
More information
e-pub ahead of print date: 29 October 2007
Published date: January 2008
Keywords:
variable region, region, variant, malaria, synthetic peptides, repair, capsular polysaccharide, b meningococci, dna, genetic immunization, immune-response, fusion, immune response, peptide, vaccine, time, infection, outer-membrane protein, protein, protective antibodies, induction
Organisations:
Cancer Sciences, Infection Inflammation & Immunity
Identifiers
Local EPrints ID: 62977
URI: http://eprints.soton.ac.uk/id/eprint/62977
ISSN: 0019-9567
PURE UUID: f8069f39-d6bb-4491-8872-8daace6c7963
Catalogue record
Date deposited: 12 Sep 2008
Last modified: 16 Mar 2024 02:54
Export record
Altmetrics
Contributors
Author:
Delin Zhu
Author:
Jeannette N. Williams
Author:
Jason Rice
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
