Oral vaccination with live Mycoplasma pneumoniae elicits a respiratory protective immunity in a murine model.

Vaccine development targeting Mycoplasma pneumoniae began in the 1960s, but achieving safe and effective immunization is still challenging. Careful consideration of the immunization pathway is one of the critical aspects of vaccine development. In this investigation, C57BL/6 J mice were intragastrically vaccinated with live M. pneumoniae, and the short-term safety and resultant immune effects were evaluated. Oral administration likely demonstrated intestinal clearance with restricted systemic dissemination and no tissue pathogenicity in both the intestinal and pulmonary tracts. Furthermore, the oral vaccination with live M. pneumoniae effectively reduced the pathogen burden in the lung, alleviated pulmonary inflammation, and reduced the pulmonary secretion of IL-1β and TNF-α after intranasal bacterial infection 3 or 15 weeks after the last dose. Moreover, Airway exposure to M. pneumoniae in live pathogen intragastric vaccinated mice triggered robust recall responses, marked by the elevation of systemic mycoplasma-specific IgG and IgM, alongside pulmonary mucosal IgA, paralleled by clonal expansion of Th1, Th2, and CTL. In conclusion, oral delivery presents a promising route for developing M. pneumoniae vaccines.