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Intranasal immunization with acellular pertussis vaccines results in long-term immunity to Bordetella pertussis in mice

Wolf, MA;Boehm, DT;DeJong, MA;Wong, TY;Sen-Kilic, E;Hall, JM;Blackwood, CB;Weaver, KL;Kelly, CO;Kisamore, CA;Bitzer, GJ;Bevere, JR;Barbier, M;Damron, FH;

Bordetella pertussis colonizes the respiratory mucosa of humans, inducing an immune response seeded in the respiratory tract. An individual, once convalescent, exhibits long-term immunity to the pathogen. Current acellular pertussis (aP) vaccines do not induce the long-term immune response observed after natural infection in humans. In this study, we evaluated the durability of protection from intranasal (IN) pertussis vaccines in mice. Mice that convalesced from B. pertussis infection served as a control group. Mice were immunized with a mock vaccine (PBS), aP only, or an aP base vaccine combined with one of the following adjuvants: alum, curdlan, or purified whole glucan particle (IRI-1501). We utilized two study designs: short-term (challenged 35 days post-priming vaccination) and long-term (challenged six months post-boost). The short-term study demonstrated that immunization with IN vaccine candidates decreased bacterial burden in the respiratory tract, reduced markers of inflammation, and induced significant serum and lung antibody titers. In the long-term study, protection from bacterial challenge mirrored the results observed in the short-term challenge study. Immunization with pertussis antigens alone was surprisingly protective in both models; however, the alum and IRI-1501 adjuvants induced significant B. pertussis specific IgG antibodies in both the serum and lung, and increased numbers of anti-B. pertussis IgG secreting plasma cells in the bone marrow. Our data indicate that humoral responses induced by the IN vaccines correlated with protection, suggesting that long-term antibody responses can be protective.