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

ASENSIO, CRISTIAN; GAILLARD, M. EMILIA; MORENO, GRISELDA; BOTTERO, DANIELA; ZURITA, MARIA EUGENIA; RUMBO, MARTIN; VAN DER LEY, PETER; VAN DER ARK, ARNO; HOZBOR, DANIELA

VACCINE

ELSEVIER SCI LTD

Año: 2011 vol. 29 p. 1649 - 1656

0264-410X

In an effort to devise a safer and effective pertussis acelullar vaccine, outer membrane vesicles (OMVs) were engineered to decrease their endotoxicity. ThepagL gene fromBordetella bronchiseptica, which encodes a lipid A 3-deacylase, was expressed inBordetella pertussisstrain Tohama I. The resulting OMVs, designated OMVsBpPagL, contain tetra- instead of penta-acylated LOS, in addition to pertussis surface immunogens such as pertactin and pertussis toxin, as the wild type OMVs. The characterized pertussis OMVsBpPagLwere used in murineB. pertussisintranasal (i.n.) challenge model to examine their protec-tive capacity when delivered by i.n. routes. Immunized BALB/c mice were challenged with sublethal doses ofB. 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 OMVsBpPagLand wild type OMVs. All OMV preparations tested were non toxic according to WHO criteria; however, OMVsBpPagLdisplayed 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 as well as neutrophil recruitment to airways showed coincident results, with a lower induction of the proinflammatory cytokines and lower recruitment in the case of OMVsBpPagLcompared to wild type OMVs. Given their lower endotoxic activity and retained protective capacity in the mouse model, OMVsBpPagL obtained fromB. pertussisseem as interesting candidates to be considered for the development of novel multi-antigen vaccine.