The Journal of Experimental Medicine
Torrey Pines Biolabs
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Published online 3 January 2006 doi:10.1084/jem.20051540
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 1, 111-118
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ARTICLE

 Antiidiotypic DNA vaccination induces serum bactericidal activity and protection against group B meningococci

Concetta Beninati1, Angelina Midiri1, Giuseppe Mancuso1, Carmelo Biondo1, Milena Arigò1, Elisabetta Gerace1, Salvatore Papasergi1, Maria Gambuzza1, Mauro Boretti1, Walter Magliani2, Stefania Conti2, Luciano Polonelli2, and Giuseppe Teti1

1 Dipartimento di Patologia e Microbiologia Sperimentale, Università degli Studi di Messina, I-98125 Messina, Italy
2 Dipartimento di Patologia e Medicina di Laboratorio, Sezione di Microbiologia, Università degli Studi di Parma, I-43100 Parma, Italy

CORRESPONDENCE Giuseppe Teti: teti{at}eniware.it

No vaccine is available for preventing infections by serogroup B Neisseria meningitidis (MenB), which accounts for a major portion of meningococcal cases in developed countries, because of the poor immunogenicity of the capsular polysaccharide (CP) even after protein conjugation. We have previously induced anticapsular antibodies by immunization with a single chain variable fragment (scFv), which mimics a protective CP epitope. This surrogate antigen, however, was ineffective at inducing serum bactericidal activity, an accepted marker of protection in humans. Serum bactericidal activity was consistently achieved by immunizing mice with the scFv-encoding gene. Immunization with vectors without a secretory signal sequence before the scFv resulted in markedly higher bactericidal activity relative to those with such a sequence. The induced antibodies were capsule specific, as shown by complete inhibition of bactericidal activity by purified MenB CP and by resistance to killing of MenA or MenC. Moreover, these antibodies were predominantly of the IgG2a isotype, reflecting a T helper type 1 response. Administration of sera from scFv gene–vaccinated animals protected infant rats against MenB bacteremia. These data illustrate the potential of vaccination with genes encoding capsular mimics in providing protection against MenB and other encapsulated bacteria.

Abbreviations used: ANOVA, analysis of variance; CEA, carcinoembryonic antigen; CP, capsular polysaccharide; MenB, serogroup B Neisseria meningitidis; N-Pr MenB, N-propionylated MenB CP; PSA, polysialic acid; scFv, single chain variable fragment; TT, tetanus toxoid.


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