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.

Pertussis Vaccines Scarcely Provide Protection against Bordetella parapertussis Infection in Children—A Systematic Review and Meta-Analysis

“…The lipopolysaccharide (LPS)-O antigen was identified as a critical protective antigen of B. parapertussis in a mouse model [ 54 ]. Studies have shown that outer membrane vesicles (OMVs) from B. pertussis , which incorporate the LPS-O antigen from B. parapertussis , effectively protect mice against infections caused by both pathogens [ 55 ]. This approach can significantly expand the effectiveness of pertussis vaccination programs, ensuring comprehensive protection against both pathogens.…”

No innocent bystanders: pertussis vaccination epitomizes evolutionary parallelisms betweenBordetella parapertussisandB. pertussis

“…This evolution leaves only FHA as an aVP vaccine antigen expressed by Bpp , against which the bactericidal activity of antibodies is weak [49]. Future improved whooping cough vaccines could benefit from comprising Bp-Bpp cross-reacting antigens explicitly, such as the adenylate cyclase [58] or conserved antigens identified through immune-informatics [59], or could incorporate Bpp -specific antigens, such as the O-antigen [60].…”

Bacterial Outer Membrane Vesicles (OMVs)-Based Dual Vaccine for Influenza A H1N1 Virus and MERS-CoV

“…This emphasize the synergistic effect of humoral and cellular immunities secreted upon vaccination with the chimeric OMVs-H1/RBD formulation. Serum transfer experiments would be able to further elucidate the role of humoral immunity independent of cellular immunity [49].…”