O antigen allows <i>B. parapertussis</i> to evade <i>B. pertussis</i> vaccine-induced immunity by blocking binding and functions of cross-reactive antibodies

Abstract

Although the prevalence of <i>Bordetella parapertussis</i> varies dramatically among studies in different populations with different vaccination regimens, there is broad agreement that whooping cough vaccines, composed only of <i>B. pertussis</i> antigens, provide little if any protection against <i>B. parapertussis</i>. In C57BL/6 mice, a <i>B. pertussis</i> whole-cell vaccine (wP) provided modest protection against <i>B. parapertussis</i>, which was dependent on IFN-γ. The wP was much more protective against an isogenic <i>B. parapertussis</i> strain lacking O-antigen than its wild-type counterpart. O-antigen inhibited binding of wP-induced antibodies to <i>B. parapertussis</i>, as well as antibody-mediated opsonophagocytosis <i>in vitro</i> and clearance <i>in vivo</i>. aP-induced antibodies also bound better <i>in vitro</i> to the O-antigen mutant than to wild-type <i>B. parapertussis</i>, but aP failed to confer protection against wild-type or O antigen-deficient <i>B. parapertussis</i> in mice. Interestingly, <i>B. parapertussis</i>-specific antibodies provided in addition to either wP or aP were sufficient to very rapidly reduce <i>B. parapertussis</i> numbers in mouse lungs. This study identifies a mechanism by which one pathogen escapes immunity induced by vaccination against a closely related pathogen and may explain why <i>B. parapertussis</i> prevalence varies substantially between populations with different vaccination strategies.