Abstract
The pioneer human oral commensal bacterium Streptococcus mitis has unique biologic features that make it an attractive mucosal vaccine or therapeutic delivery vector. S. mitis is safe as a natural persistent colonizer of the mouth, throat and nasopharynx and the oral commensal bacterium is capable of inducing mucosal antibody responses. A recombinant S. mitis (rS. mitis) that stably expresses HIV envelope protein was generated and tested in the germ-free mouse model to evaluate the potential usefulness of this vector as a mucosal vaccine against HIV. Oral vaccination led to the efficient and persistent bacterial colonization of the mouth and the induction of both salivary and systemic antibody responses. Interestingly, persistently colonized animals developed antigen-specific systemic T cell tolerance. Based on these findings we propose the use of rS. mitis vaccine vector for the induction of mucosal antibodies that will prevent the penetration of the mucosa by pathogens such as HIV. Moreover, the first demonstration of rS. mitis having the ability to elicit T cell tolerance suggest the potential use of rS. mitis as an immunotherapeutic vector to treat inflammatory, allergic and autoimmune diseases.
Highlights
Streptococcus mitis is a commensal species of Gram-positive oral streptococci that inhabits the human mouth
Persistent colonization by rS. mitis induced T cell non-responsiveness to antigen stimulation, which is likely due to the induction of oral T cell tolerance. These findings suggest that an rS. mitis vector prototype is capable of colonizing oral mucosal surfaces and inducing mucosal and systemic antibody responses, which argue in favor of further development of rS. mitis vaccine strategy to elicit protective mucosal and systemic antibodies against HIV and other mucosal pathogens
S. mitis was transformed by electroporation with p5E3 to generate homologous recombinant S. mitis expressing HIV-1 Env or with pCR2.1 containing Ermr flanked by 250bp pulA 5’ and 3’ fragments to generate control S. mitis empty vector. rS. mitis clones were selected on Todd Hewitt Broth (THB) plates containing 50 μg/ml erythromycin (Fisher Scientific, Pittsburgh, PA)
Summary
Streptococcus mitis is a commensal species of Gram-positive oral streptococci that inhabits the human mouth. S. mitis and other oral commensal streptococci including S. salivarius and S. oralis are among the first colonizers of the human mouth; they are called pioneer oral bacteria. 21, 2012, Title: A Vaccine and Therapeutic Delivery System, Inventors: Antonio Campos-Neto, Margaret Duncan and Mark Cayabyab. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. An extensive microbiota study showed that during infancy and adult life, S. mitis can predominate, both in prevalence and proportion of oral streptococci recovered in the mouth [5] and S. mitis was the most predominant bacterial species colonizing all oral surfaces of adults [6]. Some strains of S. mitis and other oral streptococci express IgA1 protease that cleaves host neutralizing IgA antibodies [3, 4]
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