Resistance of Young Mice to Pneumococcal Infection can be Improved by Oral Vaccination with Recombinant Lactococcus lactis

Abstract

Background/Purpose: Oral immunization with Lactococcus lactis PppA (LPA+), a recombinant strain that is able to express the pneumococcal protective protein A, can improve the resistance to respiratory challenge with Streptococcus pneumoniae in adult mice. In this study, we investigated whether oral immunization protocols using LPA+ are able to protect young mice against pneumococcal respiratory infection. Methods: Young mice (aged, 3 weeks) were immunized orally with LPA+ for 5 consecutive days. Vaccination was performed once (non-boosted group), or twice with a 2-week interval between each immunization (boosted group). At the end of treatment, the specific immune responses and the resistance to pneumococcal infection were studied. Results: We found that the oral immunization with LPA+ was able to induce the production of specific antibodies in the respiratory and intestinal tracts as well as systemically. Analysis of IgG subtypes showed that LPA+ immunization stimulated a mixed Th1 and Th2 response. To assess whether the production of mucosal and systemic antibodies was able to afford protection against respiratory pneumococcal infection, challenge experiments with the pathogenic serotypes 3, 6B, 14, and 23F were carried out. Vaccination with LPA+ was able to increase resistance to infection with the four serotypes of S. pneumoniae, although the protective capacity of the experimental vaccine was different for each of them. Immunization decreased colonization in the lung, prevented bacteremia of serotypes 6B, 14, and 23F, and decreased colony counts of serotype 3. Conclusion: We have shown that the oral immunization of young mice with LPA+ effectively induces the production of specific antibodies against the antigen PppA, both in mucosae and at the systemic level. The antibodies produced may play an important role in the protection against pneumococcal disease, since the young mice immunized with the experimental vaccine showed an increased resistance to infection with different serotypes of the pathogen.