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

ASENSIO CHRISTIAN; EMILIA GAILLARD; GRISELDA MORENO; DANIELA BOTTERO; ZURITA EUGENIA; MARTIN RUMBO; PETER VAN DER LEE; ARNO VAN DER ARK; DANIELA HOZBOR

VACCINE

ELSEVIER SCI LTD

Año: 2011 p. 1649 - 1656

0264-410X

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> 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 OMVs PagL 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 OMVs PagL and wild type OMVs. All OMV preparations tested were non toxic according to WHO criteria, however, OMVs PagL 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 OMVs PagL 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.