Oral immunization with recombinant Lactococcus lactis confers protection against respiratory pneumococcal infection

VILLENA JULIO; MARCELA MEDINA; RAYA RAÚL; ALVAREZ SUSANA

CANADIAN JOURNAL OF MICROBIOLOGY

NRC Reserach Press

Lugar: Saskatoon, Canada; Año: 2008 vol. 54 p. 845 - 853

0008-4166

In the present work we evaluated if the oral immunization with the pneumococcal protective protein A (PppA), expressed in the cell wall of L. lactis (L. lactis PppA+), was able to confer protective immunity against S. pneumoniae. Mice were immunized orally with L. lactis PppA+ for five consecutive days. Vaccination was performed one (non-boosted group) or two times with a two-week interval between each immunization (boosted group). Oral priming with L. lactis PppA+ induced the production of anti-PppA IgM, IgG and IgA antibodies in serum, bronchoalveolar (BAL) and intestinal (IF) lavage fluids. Boosting with L. lactis PppA+ increased the levels of mucosal and systemic immunoglobulins. Moreover, the avidity and the opsonophagocytic activity of anti-PppA antibodies were significantly improved in the boosted group. The presence of both IgG1 and IgG2a anti-PppA antibodies in serum and BAL and the production of both INF-g and IL-4 by spleen cells from immunized mice indicated that L. lactis PppA+ stimulated a mixture of Th1 and Th2 response. The ability L. lactis PppA+ to confer cross protective immunity was evaluated using challenge assays with serotypes 3, 6B, 14 and 23F. Lung bacterial cell counts and hemocultures showed that immunization with L. lactis PppA+ improved resistance against all the serotypes assessed, including serotype 3 which was highly virulent in our experimental animal model. This is, to our knowledge, the first demonstration of protection against respiratory pneumococcal infection induced by oral administration of a recombinant lactococcal vaccine.