Evaluation of the protective effect and the adjuvant activity of Lactococcus lactis in a model of pneumococcal infection, for its potential use as vaccine vector.

ELISA VINTIÑI; MARCELA MEDINA; JULIO VILLENA; SILVIA RACEDO; SUSANA ALVAREZ

S. M. de Tucumán, Tucumán, Argentina

Simposio; II International Symposium on Lactic acid bactéria- First Argentinian LAB Net Meeting; 2006

Centro de Referencia para Lactobacilos CERELA-CONICET

Streptococcus pneumoniae is an important cause of human diseases (pneumonia, septicemia and meningitis) and it is a pathogen with high incidence in our populations. In previous works we demonstrated that preventive administration of L. lactis NZ 9000 for 5 consecutive days (108 cell/d/mouse), by oral or nasal routes, was effective to improve protection against pneumococcal infection. These treatments reduced lung bacterial cell counts and avoid (nasal) or reduced (oral) the passage of the pathogen into the blood. Objetives: To evaluate in adult Swiss-Albino mice, the effect of orally (O) and nasally (N) administered L. lactis NZ9000 (LL) by studying: A) The adjuvant capacity on the systemic and mucosal immune system in a model of mucosal pneumococcal infection (106 UFC/ratón). Studies: histopathology of lungs using hamtoxilin-eosin stain, myeloperoxidase (MPO) activity in blood and lungs, anti-pneumococcal IgA and IgG in broncoalveolar lavages (BAL) and serum by ELISA; and number of mucosal IgA+ cells. B) The protective effect in a systemic pneumococcal infection model, evaluating survival rates after an intraperitoneal challenge with 108 CFU of S. pneumoniae. C) Immune response against L. lactis by evaluation of anti-L. lactis IgG and IgA in BAL and serum by ELISA. Results: A) Nasal administration of LL allowed the recovery of lung architecture that was altered by infection and a higher MPO activity in blood and lungs (Control: 5.5±0.1; O: 8.0±0.6, N: 10.3±0.5 U/mg protein).  In addition, in this group there was a significant increase (p<0.05) of BAL anti-pneumococcal IgA and IgG and serum IgG. Oral administration of LL improved only the levels of mucosal IgG and IgA. Both treatments increased the number of mucosal IgA+ cells, however nasal administration showed significantly (p<0.05) higher numbers when compared with the other groups (C: 105±2, O: 130±3 N: 162±2 cells/10 fields). B) Nasal administration of LL increased significatly (p<0.05) the survival of mice infected by intraperitoneal route with S. pneumoniae, when compared with the control group (C: 20% of survival, O: 50%, N: 70%) C) There was no immune response to L. lactis since serum and BAL anti-L. lactis IgA and IgG were no detected. Conclusions: The “per se” adjuvant effect of L. lactis and the absence of a response against itself, would allow its use as a live vaccine vector for the prevention of S. pneumoniae infection.