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

ABSTRACT: 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.

SUBMITTER: Beninati C

PROVIDER: S-EPMC2118089 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature

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

Beninati Concetta C Midiri Angelina A Mancuso Giuseppe G Biondo Carmelo C Arigò Milena M Gerace Elisabetta E Papasergi Salvatore S Gambuzza Maria M Boretti Mauro M Magliani Walter W Conti Stefania S Polonelli Luciano L Teti Giuseppe G

The Journal of experimental medicine 20060103 1

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 b ...[more]

PMID: 16390937

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Project description:Caesalpinia crista is a medicinal herb used to cure various ailments in subtropical and tropical regions of Southeast Asia.The objective of this evaluation of C. crista against free radical induced DNA and erythrocyte damage.The profiles of polyphenol and flavonoid were quantified through reversed-phase high-performance liquid chromatography. Free radical induced DNA and membrane damage were performed using H2O2 as oxidative agent.The total polyphenol content of C. crista leaf ethyl acetate extract (CcEA) was 94.5 ± 3.8 mg/gGAE, CcME (C. crista leaf methanol extract) was 52.7 ± 2.8 mg/gGAE, and CcWE (C. crista leaf Water extract) was 31.84 ± 1.8 mg/gGAE. Total flavonoid content of CcEA was 60.46 ± 2.3 mg/gQE, CcME was 46.26 ± 1.8 mg/gQE, and CcWE was 20.47 ± 1.1 mg/gQE. The extracts also exhibited good antioxidant activity as confirmed by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid), hydroxyl scavenging, reducing power, and total antioxidant assays. Among the three extracts, CcEA and CcME showed better protection against red blood cell (RBC) hemolysis and DNA damage as confirmed by electrophoretic study. Further, Scanning electron micrograph data showed that CcEA revealed the free radical induced structural alterations in RBC.These findings suggest that C. crista contains bioactive molecules and can inhibit oxidative stress and can be source of further study to use this in herbal medicine.ROS are generated under normal biological systems. These ROS generated can be scavenged by endogenous and exogenous cellular mechanisms. Environmental stress, radiation, smoke etc. elevates ROS dramatically. This leads to significant damage to cellular biomolecules like DNA and cell structures. Plants as a large reservoir of drugs for protecting DNA and cell structures from oxidative stress. Polyphenols present in the C. crista extracts acts through several mechanisms to quench free radicals. Extracts exhibited potent antioxidant properties and also protected DNA and cell membrane from oxidative damage. Hence this can be used in herbal medicine for treating oxidative stress mediated diseases. Abbreviations used: ABTS: 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid); CcEA: C. crista leaf ethyl acetate extract; CcME: C. crista leaf methanol extract; CcWE: C. crista leaf Water extract; DPPH: 2,2-diphenyl-1-picrylhydrazyl; GAE: Gallic acid Equivalent; H2O2: Hydrogen Peroxide; QE: Quercetin Equivalent; RNS: Reactive Nitrogen Spevcies; ROS: Reactive Oxygen Species; SEM: Scanning Electron Microscope.

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Dataset Information

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

Publications

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

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