Articulo
Outer-Membrane-Vesicle-Associated O Antigen, a Crucial Component for Protecting Against Bordetella parapertussis Infection
Autor
Bottero, Daniela
Zurita, María Eugenia
Gaillard, María Emilia
Carriquiriborde, Francisco Pablo
Aispuro, Pablo Martín
Elizagaray, Maia Lina
Bartel, Erika Belén
Castuma, Celina Elisabet
Hozbor, Daniela Flavia
Institución
Resumen
<i>Bordetella parapertussis</i> is a respiratory-disease pathogen producing symptomatology similar to that of pertussis but of underestimated incidence and with no specific vaccine existing. We recently designed a vaccine candidate from <i>B. parapertussis</i> outer-membrane vesicles (OMVs) that proved to be safe and protective in a murine-infection model. Based on protection recently reported for the <i>B. parapertussis</i> O antigen in aqueous solution, we assessed here whether the <i>B. parapertussis</i> O-antigen-containing lipopolysaccharide (BppLPS-O⁺) embedded in the membranes, as present in <i>B. parapertussis</i>-derived OMVs (OMVs(Bpp-LPS-O⁺)), was the component responsible for that previously observed protection by OMVs. By performing a comparative study with OMVs from a human strain with undetectable O antigen (OMVs(Bpp-LPS-O⁻)), we demonstrated that the OMVs(Bpp-LPS-O⁺), but not the OMVs(Bpp-LPS-O⁻), protected mice against sublethal <i>B. parapertussis</i> infections. Indeed, the <i>B. parapertussis</i> loads were significantly reduced in the lungs of OMVs(Bpp-LPS-O⁺) -vaccinated animals, with the CFUs recovered being decreased by 4 log units below those detected in the non-immunized animals or in the animals treated with the OMVs(Bpp-LPS-O⁻), (p < 0.001). We detected that the OMVs(Bpp-LPS-O⁺) induced IgG antibodies against <i>B. parapertussis</i> whole-cell lysates, which immunocomponents recognized, among others, the O antigen and accordingly conferred protection against <i>B. parapertussis</i> infection, as observed in <i>in-vivo</i>-passive-transfer experiments. Of interest was that the OMVs(Bpp-LPS-O⁺) -generated sera had opsonophagocytic and bactericidal capabilities that were not detected with the OMVs(Bpp-LPS-O⁻)-induced sera, suggesting that those activities were involved in the clearance of <i>B. parapertussis</i>. Though stimulation of cultured spleen cells from immunized mice with formulations containing the O antigen resulted in gamma interferon (IFN-γ) and interleukin-17 production, spleen cells from OMVs(Bpp-LPS-O⁺) -immunized mice did not significantly contribute to the observed protection against <i>B. parapertussis</i> infection. The protective capability of the <i>B. parapertussis</i> O antigen was also detected in formulations containing both the OMVs derived from B. pertussis and purified BppLPS-O⁺. This combined formulation protected mice against B. pertussis along with <i>B. parapertussis</i>. Facultad de Ciencias Exactas Instituto de Biotecnologia y Biologia Molecular Instituto de Estudios Inmunológicos y Fisiopatológicos