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

Abstract

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. 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. 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.