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Infection and Immunity, January 2008, p. 334-338, Vol. 76, No. 1
0019-9567/08/$08.00+0     doi:10.1128/IAI.00943-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

Delin Zhu,^1, Jeannette N. Williams,² Jason Rice,¹ Freda K. Stevenson,¹ John E. Heckels,² and Myron Christodoulides^2*

Genetic Vaccine Group, Cancer Sciences Division, Somers Cancer Research Building,¹ Neisseria Research Group, Molecular Microbiology, Division of Infection, Inflammation and Repair, University of Southampton Medical School, Southampton General Hospital, Southampton SO16 6YD, United Kingdom²

Received 11 July 2007/ Returned for modification 15 August 2007/ Accepted 15 October 2007

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.

Published ahead of print on 29 October 2007.

Editor: F. C. Fang

Present address: National Engineering Centre of Cell Products and Amcellgene Co. Ltd., TEDA Science and Technology Park, Tianjin 300457, People's Republic of China.