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口腔对戈登氏链球菌的定植及免疫反应:作为诱导抗呼吸道病原体抗体载体的潜在用途。

Oral colonization and immune responses to Streptococcus gordonii: Potential use as a vector to induce antibodies against respiratory pathogens.

作者信息

Lee Song F

机构信息

Department of Applied Oral Sciences, Faculty of Dentistry, Dalhousie University, Halifax, Nova Scotia, Canada.

出版信息

Curr Opin Infect Dis. 2003 Jun;16(3):231-5. doi: 10.1097/00001432-200306000-00008.

Abstract

PURPOSE OF REVIEW

Mucosal immunization should be an excellent method of preventing respiratory infections because the local immunoglobulin A antibodies can neutralize the invading pathogens at the site of entry. Because Streptococcus gordonii, a normal inhabitant of the human oral cavity, can naturally elicit a mucosal immune response, it has been a prime candidate for investigations as a live oral vaccine vector for immunization against respiratory infections.

RECENT FINDINGS

Antigens from a number of respiratory bacteria, such as Bordetella pertussis, and one virus have been expressed extracellularly or on the cell surface of S. gordonii. The antigens expressed were single or multiple proteins from one or more pathogens. The recombinant S. gordonii expressing surface-localized heterologous antigens could colonize and persist in the oral cavity of mice and rats. Oral colonization induced a mucosal immunoglobulin A response and, in some instances, also a systemic immunoglobulin G response to the heterologous antigens. When given parenterally, the heterologous antigens generated a systemic immunoglobulin G response. These findings indicate that antigens expressed by S. gordonii are immunogenic. A new approach to the use of S. gordonii as a vaccine vector is to modulate immune responses by co-expressing cytokines with the antigen.

SUMMARY

The ability to express antigens from respiratory pathogens and induce immune responses during oral colonization suggests that S. gordonii may be developed into a live vector for oral immunization against respiratory infections. The major challenge ahead is to find ways to achieve a high level of immune response following oral colonization.

摘要

综述目的

黏膜免疫应是预防呼吸道感染的极佳方法,因为局部免疫球蛋白A抗体可在病原体入侵部位中和它们。由于戈登链球菌是人类口腔的正常寄居菌,能自然引发黏膜免疫反应,它一直是作为预防呼吸道感染的口服活疫苗载体进行研究的主要候选对象。

最新发现

来自多种呼吸道细菌(如百日咳博德特氏菌)和一种病毒的抗原已在戈登链球菌的细胞外或细胞表面表达。所表达的抗原是来自一种或多种病原体的单一或多种蛋白质。表达表面定位的异源抗原的重组戈登链球菌能够在小鼠和大鼠口腔中定殖并持续存在。口服定殖诱导了对异源抗原的黏膜免疫球蛋白A反应,在某些情况下还诱导了全身性免疫球蛋白G反应。当通过肠胃外途径给予时,异源抗原产生了全身性免疫球蛋白G反应。这些发现表明戈登链球菌表达的抗原具有免疫原性。将戈登链球菌用作疫苗载体的一种新方法是通过与抗原共表达细胞因子来调节免疫反应。

总结

在口腔定殖期间表达呼吸道病原体抗原并诱导免疫反应的能力表明,戈登链球菌可能被开发成一种用于口服免疫预防呼吸道感染的活载体。未来的主要挑战是找到在口腔定殖后实现高水平免疫反应的方法。

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