Intranasal vaccination with probiotic Escherichia coli membrane vesicles displaying pneumococcal capsular polysaccharides elicits mucosal immunity

A novel vaccine modality is needed to generate both systemic and mucosal immunity in the respiratory tract, where pathogens are most likely to colonize and to initiate infection. Here, we demonstrated that intranasal immunization with probiotic Escherichia coli-derived membrane vesicles displaying serotype-14 pneumococcal capsule (CPS14⁺MVs) elicited potent IgG responses without adjuvant in mice, which were comparable and significantly superior to those of the injected CPS14⁺MVs and two licensed pneumococcal vaccines (conjugate and polysaccharide types), respectively. Notably, IgA class-switch recombination occurred only with intranasal CPS14⁺MVs immunization, resulting in robust secretory IgA (SIgA) production throughout a one-year-long-term study. Furthermore, the intranasal CPS14⁺MV vaccine induced both systemic and mucosal immunity regardless of mouse age at vaccination. Whereas opsonophagocytic activities were detected in sera of all immunization groups, only the intranasal CPS14⁺MV vaccine achieved dramatic pneumococcal clearance in the nasal cavity. Nevertheless, it failed to protect isogenic pIgR^-/- mice, which are genetically impaired for SIgA translocation, from colonization of the respiratory tract. In conclusion, the present study could offer a novel vaccination strategy using chimeric probiotic E. coli MVs to provide antibody-mediated protection against pneumococcal colonization and infection.