XXXV Reunião Anual da SBBqResumoID:8913


Pulmonary surfactant as adjuvant in acellular pertussis vaccine


Prestes, A.F.R.O1; Horton, D.S.P.Q.1; Cainelli Gebara, V. C. B.1; Kubrusly, F. S.1; Iourtov, D.1; Esteves, M. I.1; Quintilio, W.2;  Leme, E.1; Furuyama, N.3; Sakauchi, M. A.3; Raw, I.1 and  Dias, W. O.1



1Centro de Biotecnologia; 2Seção de Controle de Qualidade; 3Seção de Vacinas Aeróbicas; Instituto Butantan


Pulmonary surfactant primary function is to reduce surface tension in the alveoli, but can also influence the immune function. In this work, the adjuvant effect of a pig lung surfactant (PLS) was evaluated in the immune response of mice to an acellular pertussis vaccine (APV), comparatively with alum (AL). Mice were immunized with: (I) APV mixed with 3 different concentrations of PLS (3.0mg/ml; 0.6mg/ml or 0.3mg/ml), by intraperitoneal (i.p) route; or (II) APV mixed with PLS (3.0mg/ml) or AL by i.p or intranasal (i.n) route. One group of animals was immunized i.p with APV and simultaneously with PLS by i.n route. The animals were boosted two weeks after the first dose, bled after 15 days and challenged by intracerebral test with a virulent Bordetella pertussis strain. The vaccine given i.p mixed with the adjuvant elicited a very high protective effect, showing a dose response curve of survival according to decreasing concentrations of PLS (100, 90 and 50% of survival, respectively). The immunization by intranasal route that is not the usual via for pertussis vaccines, elicited 60% of protection using APV mixed with PLS, but only 28.6% with alum. It was not detected serum IgG antibodies anti-pertussis toxin (PT) in the animals injected i.n. After i.p immunization, similar serum antibodies titers anti-PT were obtained, using AL or PLS as adjuvants, either when PLS was injected mixed with the vaccine or simultaneously, by i.n route. The animals immunized i.p with APV plus PLS showed levels of serum IFNγ significantly higher than the induced by the adjuvant alone, suggesting a Th1 tendency of response, what was confirmed by lower ratio of IgG1/IgG2a in this group, comparing with the injected with AL as adjuvant. Considering the side effects related to alum and its tendency to generate an antibody response Th2, without Th1, it would be interesting to consider other adjuvants  to be used with acellular pertussis vaccines, that preferentially also induce Th2 cells. The immunemodulation to Th1 response would simulate the protection elicited by native infection with B.pertussis.

 

Supported by FAPESP