Secretion ofPorphyromonas gingivalisFimbrillin Polypeptides by RecombinantStreptococcus gordonii

Sharma, Ashu; Sojar, Hakimuddin T.; Hruby, Dennis E.; Kuramitsu, Howard K.; Genco, Robert J.

doi:10.1006/bbrc.1997.7306

Cited by 16 publications

(7 citation statements)

References 17 publications

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“…Among these proteins include the C-repeat region of the S. pyogenes M6-protein (6,11,20), the human testicular tumor protein (NY-ESO-1, unpublished), and the Porphyromonas gingivalis FimA protein (17)(18)(19). To date, most of the proteins expressed using SPEX have been antigens of potential vaccine interest.…”

Section: Resultsmentioning

confidence: 99%

Expression of Active Monomeric and Dimeric Nuclease A from the Gram-Positive Streptococcus gordonii Surface Protein Expression System

Dutton

Ottum

Bolken

et al. 2000

Protein Expression and Purification

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Section: Resultsmentioning

confidence: 99%

Expression of Active Monomeric and Dimeric Nuclease A from the Gram-Positive Streptococcus gordonii Surface Protein Expression System

Dutton

Ottum

Bolken

et al. 2000

Protein Expression and Purification

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“…Further, the amount of alveolar bone loss caused by dual infection with P. gingivalis and the carrier S. gordonii strain was not significantly different from that in rats monoinfected with P. gingivalis alone. The prototype S. gordonii recombinants (SgFimA) that express biologically important epitopes of P. gingivalis fimbrillin have been described earlier (31)(32)(33). An oral coimmunization strategy involving simultaneous immunization with the SgFimN and SgFimC2 recombinants was utilized in the present study.…”

Section: Vol 69 2001mentioning

confidence: 99%

“…To develop live vectors for delivery of FimA antigen to a host mucosal immune system, we have genetically engineered Streptococcus gordonii strains that surface express biologically active N (residues 55 to 145)-and C (residues 226 to 337)-terminal polypeptide domains of P. gingivalis fimbrillin (31)(32)(33). S. gordonii is a human oral commensal that is currently being developed as a vector for delivery of vaccines against viral and bacterial pathogens (5, 9, 20-22, 27, 29).…”

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confidence: 99%

Oral Immunization with RecombinantStreptococcus gordoniiExpressingPorphyromonas gingivalisFimA Domains

et al. 2001

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Porphyromonas gingivalis, a gram-negative anaerobe, is implicated in the etiology of adult periodontitis. P. gingivalis fimbriae are one of several critical surface virulence factors involved in both bacterial adherence and inflammation. P. gingivalis fimbrillin (FimA), the major subunit protein of fimbriae, is considered an important antigen for vaccine development against P. gingivalis-associated periodontitis. We have previously shown that biologically active domains of P. gingivalis fimbrillin can be expressed on the surface of the human commensal bacterium Streptococcus gordonii. In this study, we examined the effects of oral coimmunization of germfree rats with two S. gordonii recombinants expressing N (residues 55 to 145)-and C (residues 226 to 337)-terminal epitopes of P. gingivalis FimA to elicit FimA-specific immune responses. The effectiveness of immunization in protecting against alveolar bone loss following P. gingivalis infection was also evaluated. The results of this study show that the oral delivery of P. gingivalis FimA epitopes via S. gordonii vectors resulted in the induction of FimA-specific serum (immunoglobulin G [IgG] and IgA) and salivary (IgA) antibody responses and that the immune responses were protective against subsequent P. gingivalis-induced alveolar bone loss. These results support the potential usefulness of the S. gordonii vectors expressing P. gingivalis fimbrillin as a mucosal vaccine against adult periodontitis.

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“…The organism is considered to be an attractive vector as a live-oral-vaccine vehicle (14,23). A number of heterologous antigens have been expressed in this organism as either secreted proteins (15,27) or cell wall-anchored proteins (16,17,19,20,25,26). In the murine oralcolonization model, the recombinant S. gordonii was able to establish long-term colonization (16,20).…”

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Expression of a Functional Single-Chain Variable-Fragment Antibody against Complement Receptor 1 inStreptococcus gordonii

Knight

Halperin

West

et al. 2008

Clin Vaccine Immunol

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Streptococcus gordonii, an oral commensal organism, is a candidate vector for oral-vaccine development. Previous studies have shown that recombinant S. gordonii expressing heterologous antigens was weakly immunogenic when delivered intranasally. In this study, antigen was specifically targeted to antigen-presenting cells (APC) in order to potentiate antigen-APC interactions and increase the humoral immune response to the antigen. To achieve this goal, a single-chain variable-fragment (scFv) antibody against complement receptor 1 (CR1) was constructed. Anti-CR1 scFv purified from Escherichia coli was able to bind to mouse mixed lymphocytes and bone marrow-derived dendritic cells. The in vivo function of the anti-CR1 scFv protein was assessed by immunizing mice intranasally with soluble scFv and determining the immune response against the hemagglutinin (HA) peptide located on the carboxy terminus of the scFv. The serum anti-HA immunoglobulin G (IgG) immune response was dose dependent; as little as 100 ng of anti-CR1 scFv induced a significant IgG immune response, while such a response was minimal when the animals were given an unrelated scFv. The anti-CR1 scFv was expressed in S. gordonii as a secreted protein, which was functional, as it bound to dendritic cells. Mice orally colonized by the anti-CR1-secreting S. gordonii produced an anti-HA IgG immune response, indicating that such an approach can be used to increase the immune response to antigens produced by this bacterium.Streptococcus gordonii is a commensal bacterium found in the oral cavities of humans. The organism is considered to be an attractive vector as a live-oral-vaccine vehicle (14,23). A number of heterologous antigens have been expressed in this organism as either secreted proteins (15, 27) or cell wall-anchored proteins (16,17,19,20,25,26). In the murine oralcolonization model, the recombinant S. gordonii was able to establish long-term colonization (16,20). However, there are difficulties in stimulating a strong protective immune response against recombinant antigens following oral colonization.Antigen targeting to immune cells has the potential to manipulate the immune system and elicit an immune response more efficiently. Monoclonal immunoglobulin G (IgG) antibodies have long been used as specific targeting vehicles. A number of reports have indicated success in achieving enhanced immune responses using antibodies to complement receptor 1 (CR1) and CR2 (3,8,30), Fc receptors (1, 2), and dendritic cell DEC205 receptor (5, 6). However, there are limitations in using intact IgG as a targeting vehicle; these limitations include a weak extravascular transport ability for IgG and difficulties with expressing whole IgG by bacteria. Single-chain variable-fragment (scFv) antibodies, however, offer a number of advantages, e.g., they can be readily produced by bacteria and can be easily engineered genetically as fusion proteins carrying polypeptide antigens. In the context of antigen targeting, scFvs against CR1 and -2 (21, 24), DEC205 (9), CD3 (31), a...

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Secretion ofPorphyromonas gingivalisFimbrillin Polypeptides by RecombinantStreptococcus gordonii

Cited by 16 publications

References 17 publications

Expression of Active Monomeric and Dimeric Nuclease A from the Gram-Positive Streptococcus gordonii Surface Protein Expression System

Expression of Active Monomeric and Dimeric Nuclease A from the Gram-Positive Streptococcus gordonii Surface Protein Expression System

Oral Immunization with RecombinantStreptococcus gordoniiExpressingPorphyromonas gingivalisFimA Domains

Expression of a Functional Single-Chain Variable-Fragment Antibody against Complement Receptor 1 inStreptococcus gordonii

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