Intranasal Immunization with Acellular Pertussis Vaccines Results in Long-Term Immunity to Bordetella pertussis in Mice

Abstract

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.

Mucosal Immunization Against Pertussis: Lessons From the Past and Perspectives

“…Instead, it appeared to suppress IgA responses in the nasal secretions, which, however, did not impair protection against nasal colonization. Importantly, compared to non-vaccinated controls, a significant reduction in bacterial burden in lungs, trachea and nasal tissues could still be observed 6 months after two intranasal administrations of curdlan-formulated aPV ( 28 ). This reduction in bacterial burden was correlated with the persistence of B. pertussis -specific antibody levels in lung and serum.…”

Mucosal immunization with DTaP confers protection against Bordetella pertussis infection and cough in Sprague-Dawley rats

“…While no CoP has yet to be fully agreed upon against pertussis in humans, anti-PT IgG levels >5 IU/ml are associated with protection in humans (74). In mice, IN administration of DTaP induced anti-Bp, anti-FHA, and anti-PT IgG antibodies while wP vaccination induced serum anti-Bp IgG antibodies that correlated with protection against Bp (28,57). Here in our study, we generated correlograms between all vaccinated groups to identify correlations between variables in the coughing rat model of pertussis, which has yet to be established (Fig.…”

“…Mucosal immunization has been of particular interest in the pertussis field. We and others have recently evaluated intranasal immunization of DTaP in Bp challenged mice (27,28,(64)(65)(66).…”

“…Nonhuman primates previously infected with Bp generate both Th1 and Th17 memory cells that are still detected two years post infection (25). To induce a similar protective immune response that is observed during natural infection, mucosal vaccination has recently been investigated (26)(27)(28) Mucosal immunization has been scarcely used as a vaccination strategy to generate a protective immune response against pertussis in clinical and pre-clinical models. Oral vaccination with wP induced the production of Bp specific antibody titers in both the saliva and serum of newborns (29).…”

“…Nonhuman primates previously infected with Bp generate both Th1 and Th17 memory cells that are still detected two years post infection (25). To induce a similar protective immune response that is observed during natural infection, mucosal vaccination has recently been investigated (26–28)…”