Outer-Membrane-Vesicle-Associated O Antigen, a Crucial Component for Protecting Against Bordetella parapertussis Infection.

Abstract

Bordetella parapertussis 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 B. parapertussis outer-membrane vesicles (OMVs) that proved to be safe and protective in a murine-infection model. Based on protection recently reported for the B. parapertussis O antigen in aqueous solution, we assessed here whether the B. parapertussis O-antigen-containing lipopolysaccharide (BppLPS-O+) embedded in the membranes, as present in B. parapertussis-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 B. parapertussis infections. Indeed, the B. parapertussis 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 B. parapertussis whole-cell lysates, which immunocomponents recognized, among others, the O antigen and accordingly conferred protection against B. parapertussis infection, as observed in in-vivo-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 B. parapertussis. 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 B. parapertussis infection. The protective capability of the B. parapertussis 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 B. parapertussis.

• Authors: Daniela Bottero, María Eugenia Zurita, María Emilia Gaillard, Francisco Carriquiriborde, Pablo Martin Aispuro, Maia Elizagaray, Erika Bartel, Celina Castuma, Daniela Hozbor
• Journal: Frontiers in immunology (Front Immunol) Vol. 9 Pg. 2501 ( 2018) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 30459769 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bacterial
• Bacterial Outer Membrane Proteins
• Bacterial Vaccines
• Interleukin-17
• O Antigens
• Interferon-gamma

Topics

• Animals
• Antibodies, Bacterial (blood)
• Bacterial Outer Membrane Proteins (metabolism)
• Bacterial Vaccines (immunology)
• Bordetella Infections (immunology)
• Bordetella parapertussis (physiology)
• Bordetella pertussis (physiology)
• Cell-Derived Microparticles (metabolism)
• Disease Resistance
• Female
• Humans
• Immunity, Heterologous
• Immunization, Passive
• Interferon-gamma (metabolism)
• Interleukin-17 (metabolism)
• Lymphocyte Activation
• Mice
• Mice, Inbred BALB C
• O Antigens (immunology, metabolism)
• Vaccination