Immunogenicity of CTLA4 fusion anti-caries DNA vaccine in rabbits and monkeys

Jia, Rong; Guo, Jihua; Fan, M.W.; Bian, Zhuan; Chen, Zhi; Fan, Bing; Yu, Fei; Xu, Qing

doi:10.1016/j.vaccine.2006.03.090

Cited by 35 publications

(42 citation statements)

References 34 publications

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“…Thereafter, various cell-surface antigens of mutans streptococci and their recombinant fragments or even synthetic peptides have been studied as possible candidates for dental caries vaccines [28,29]. In the recent decade, attention has become focused on three protein antigens: the surface fibrillar adhesins, the glucosyltransferases (GTF) and the glucan-binding proteins, all of which have demonstrable associations with virulence and the process of tooth surface colonization [8,12,[30][31][32]. It is demonstrated that the streptococcal surface fibrillar adhesins control attachment to tooth surfaces, the glucosyltransferases produce adhesive glucans from sucrose, and the cell-wall-associated glucan-binding proteins have the ability to bind α-1,6-glucan and may provide the receptors for glucan-mediated aggregation [33].…”

Section: Effective Targets For Anti-caries Vaccinesmentioning

confidence: 99%

“…Many kinds of vaccine immunogens such as protein, recombinant or synthetic peptide, protein-carbohydrate conjugate, or DNA-based active vaccines and mucosal adjuvants such as heat-labile enterotoxins (HLT) from Vibrio cholera (LT-I) or Escherichia coli (LT-II), bupivacaine, chitosan have been successful in animal models [7][8][9][10][11][12]. However, no vaccines have been brought to market till now mainly due to the low ability to induce and maintain protective antibody in oral fluids.…”

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confidence: 99%

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Salivary IgA enhancement strategy for development of a nasal-spray anti-caries mucosal vaccine

Yan

2013

Sci. China Life Sci.

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Dental caries remains one of the most common global chronic diseases caused by Streptococcus mutans, which is prevalent all over the world. The caries prevalence of children aged between 5-6 years old in China is still in very high rate. A potent and effective anti-caries vaccine has long been expected for caries prevention but no vaccines have been brought to market till now mainly due to the low ability to induce and maintain protective antibody in oral fluids. This review will give a brief historical retrospect on study of dental caries and pathogenesis, effective targets for anti-caries vaccines, oral immune system and immunization against dental caries. Then, salivary IgA antibodies and the protective responses are discussed in the context of the ontogeny of mucosal immunity to indigenous oral streptococcal. The methods and advancement for induction of specific anticaries salivary sIgA antibodies and enhancement of specific anti-caries salivary sIgA antibodies by intranasal immunization with a safe effective mucosal adjuvant are described. The progress in the enhancement of salivary sIgA antibodies and anticaries protection by intranasal immunization with flagellin-PAc fusion protein will be highlighted. Finally, some of the main strategies that have been used for successful mucosal vaccination of caries vaccine are reviewed, followed by discussion of the mucosal adjuvant choice for achieving protective immunity at oral mucosal membranes for development of a nasal-spray or nasal-drop anti-caries vaccine for human. mutans streptococci, secretory IgA, PAc, mucosal immunization, caries vaccine Citation:Yan H M. Salivary IgA enhancement strategy for development of a nasal-spray anti-caries mucosal vaccine.

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Section: Effective Targets For Anti-caries Vaccinesmentioning

confidence: 99%

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confidence: 99%

Salivary IgA enhancement strategy for development of a nasal-spray anti-caries mucosal vaccine

Yan

2013

Sci. China Life Sci.

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“…The anti-caries DNA vaccine pGJA-P/VAX was constructed in our laboratory as described before [10] . Briefly, pGJA-P comprised four protein-coding sequences: the signal peptide and extracellular regions of the human CTLA4 gene, the hinge and Fc regions of the human Igγ 1 gene, the A-P region of pac gene from S mutans, and the GLU region of gtfB gene from S mutans.…”

Section: Plasmidsmentioning

confidence: 99%

“…In light of advances in DNA vaccines and a public health imperative to prevent prevalent dental caries [2] , we previously developed an anti-caries DNA vaccine pGJA-P/VAX [7] . The targeted fusion anti-caries DNA vaccine generates considerable specific immune responses in several experimental animals, such as mice [7] , hamsters [8] , rats [9] , and rabbits [10] . Protection against attacks of cariogenic microorganisms has also been reported [9] .…”

Section: Introductionmentioning

confidence: 99%

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Good Manufacturing Practices production and analysis of a DNA vaccine against dental caries

Yang

Zhang

et al. 2009

Acta Pharmacol Sin

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Aim: To prepare a clinical-grade anti-caries DNA vaccine pGJA-P/VAX and explore its immune effect and protective efficacy against a cariogenic bacterial challenge. Methods: A large-scale industrial production process was developed under Good Manufacturing Practices (GMP) by combining and optimizing common unit operations such as alkaline lysis, precipitation, endotoxin removal and column chromatography. Quality controls of the purified bulk and final lyophilized vaccine were conducted according to authoritative guidelines. Mice and gnotobiotic rats were intranasally immunized with clinical-grade pGJA-P/VAX with chitosan. Antibody levels of serum IgG and salivary SIgA were assessed by an enzyme-linked immunosorbent assay (ELISA), and caries activity was evaluated by the Keyes method. pGJA-P/VAX and pVAX1 prepared by a laboratory-scale commercial kit were used as controls. Results: The production process proved to be scalable and reproducible. Impurities including host protein, residual RNA, genomic DNA and endotoxin in the purified plasmid were all under the limits of set specifications. Intranasal vaccination with clinical-grade pGJA-P/ VAX induced higher serum IgG and salivary SIgA in both mice and gnotobiotic rats. While in the experimental caries model, the enamel (E), dentinal slight (Ds), and dentinal moderate (Dm) caries lesions were reduced by 21.1%, 33.0%, and 40.9%, respectively. Conclusion: The production process under GMP was efficient in preparing clinical-grade pGJA-P/VAX with high purity and intended effectiveness, thus facilitating future clinical trials for the anti-caries DNA vaccine.

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Biodistribution and expression of targeted fusion anti‐caries DNA vaccine pGJA‐P/VAX in mice

Liu

Fan

et al. 2008

The Journal of Gene Medicine

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Immunogenicity of CTLA4 fusion anti-caries DNA vaccine in rabbits and monkeys

Cited by 35 publications

References 34 publications

Salivary IgA enhancement strategy for development of a nasal-spray anti-caries mucosal vaccine

Salivary IgA enhancement strategy for development of a nasal-spray anti-caries mucosal vaccine

Good Manufacturing Practices production and analysis of a DNA vaccine against dental caries

Biodistribution and expression of targeted fusion anti‐caries DNA vaccine pGJA‐P/VAX in mice

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