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

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

Congreso; 1st. French-Argentinean Congress of Immunology, November 2-5, 2010. Buenos Aires, Argentina.; 2010

<!-- /* Font Definitions */ @font-face {font-family:"Arial Narrow"; panose-1:2 11 5 6 2 2 2 3 2 4; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:647 0 0 0 159 0;} /* 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;} --> he use of outer membrane vesicles as antigen for vaccination against Bordetella pertussis seems an attractive option since these vesicles harbor an important number of different bacterial antigens, including all the vaccinal antigens used for acellular commercial vaccines in the membrane context, hence in their native state. 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 (177,40 ± 1,09 vs  193,39 ± 1,47fold increase) and IL1 (10,51±4,98 vs 17,70 ± 3,70 fold increase) 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.