Outer membrane vesicles obtained from Bordetella pertussisTohama expressing the lipid A deacylase PagL as a novel acellular vaccine candidate

GAILLARD ME.; ASENSIO,CRISTIANJ; GRISELDA MORENO; BOTTERO D; MARTÍN RUMBO; VANDERLEY,PETER; VANDERARK,2ARNO; HOZBOR D.

Buenos Aires - Argentina

Congreso; First French-Argentine Inmunology Congress; 2010

Outer membrane vesicles obtained from Bordetella pertussis Tohama expressing the lipid A deacylase PagL as a novel acellular vaccine candidate. Gaillard,1María Emilia; Asensio, Cristian J.; Moreno,3Griselda; Bottero, Daniela; Rumbo,3 Martin; van der Ley,2 Peter; van der Ark,2Arno; Hozbor, Daniela. 1 Instituto de Biotecnología y Biología Molecular (IBBM). Facultad de Ciencias Exactas. Universidad Nacional de La Plata. Centro Científico Tecnológico CONICET La Plata. Calles 47 y 115. 1900. La Plata. Argentina. 2 Netherlands Vaccine Institute, 3720 AL Bilthoven, The Netherlands 3 Laboratorio de Investigaciones del Sistema Inmune (LISIN). Facultad de Ciencias Exactas, UNLP 47 y 115 (1900) La Plata, Argentina   Affiliation megaillard@biol.unlp.edu.ar   In an effort to devise a safer and effective pertussis acelullar vaccine, outer membrane vesicles (OMVs) were engineered to decrease their endotoxicity. The pagL gene from Bordetella bronchiseptica, which encodes a lipid A 3-deacylase, was expressed in B. pertussis strain Tohama I. The resulting OMVs, designated OMVsPagL, contain tetra- instead of penta-acylated LPS, in addition to pertussis surface immunogens such as pertactin and pertussis toxin, as the wild type OMVs. The characterized pertussis OMVsPagL were used in murine B. pertussis intranasal (i.n.) challenge model to examine their protective capacity when delivered by i.n routes. Immunized BALB/c mice were challenged with sublethal doses of B. pertussis. Significant differences between immunized animals and the PBS treated group were observed (p < 0.001). Adequate elimination rates (p < 0.005) were observed in mice immunized either with OMVsPagL and wild type OMVs. All OMV preparations tested were non toxic according to WHO criteria; however, OMVsPagL displayed almost no weight loss at 3 days post administration, indicating less toxicity when compared with wild type OMVs. Induction of IL6- and IL1 expression in lung after i.n. delivery showed coincident results, with a lower induction of the proinflammatory cytokines in the case of OMVsPagL compared to wild type OMVs. In view to their lower endotoxic activity and retained protective capacity in the mouse model, OMVsPagL obtained from B pertussis are candidates for novel vaccines against pertussis.