Abstract
Over two decades ago acellular pertussis vaccines (aP) replaced whole cell pertussis vaccines (wP) in several countries. Since then, a resurgence in pertussis has been observed, which is hypothesized to be linked, in part, to waning immunity. To better understand why waning immunity occurs, we developed a long-term outbred CD1 mouse model to conduct the longest murine pertussis vaccine studies to date, spanning out to 532 days post primary immunization. Vaccine-induced memory results from follicular responses and germinal center formation; therefore, cell populations and cytokines involved with memory were measured alongside protection from challenge. Both aP and wP immunization elicit protection from intranasal challenge by decreasing bacterial burden in both the upper and lower airways, and by generation of pertussis specific antibody responses in mice. Responses to wP vaccination were characterized by a significant increase in T follicular helper cells in the draining lymph nodes and CXCL13 levels in sera compared to aP mice. In addition, a population of B. pertussis + memory B cells was found to be unique to wP vaccinated mice. This population peaked post-boost, and was measurable out to day 365 post-vaccination. Anti-B. pertussis and anti-pertussis toxoid antibody secreting cells increased one day after boost and remained high at day 532. The data suggest that follicular responses, and in particular CXCL13 levels in sera, could be monitored in pre-clinical and clinical studies for the development of the next-generation pertussis vaccines.
Highlights
Pertussis is a vaccine-preventable respiratory disease caused by the Gram-negative bacterium Bordetella pertussis [1]
We describe immunological memory markers that are significantly increased in whole cell pertussis vaccines (wP) and not acellular pertussis vaccines (aP) immunization, such as CXCL13 and antigen-specific memory B cell production
We set out to establish a long-term pertussis immunization and challenge model to evaluate the duration of immunity and identify additional factors that contribute to either wP protection or the inadequate responses of aPs
Summary
Pertussis (whooping cough) is a vaccine-preventable respiratory disease caused by the Gram-negative bacterium Bordetella pertussis [1]. Whole cell pertussis vaccines (DTP/wP) were first developed and implemented in 1914, but did not become widely available for distribution until the 1940s [1, 2] After their implementation in the United States, DTP vaccines dramatically reduced pertussis disease from ~200,000 cases a year in the 1930s to ~2,000 in the 1970s [1]. Fluctuation of pertussis incidence is hypothesized to be in part due to waning in immunity elicited by the current aP vaccines. This is illustrated by an increase in incidence rates and risk ratios for pertussis in between boosters during adolescence in aP vaccinated individuals [11,12,13]. The pertussis field has several hypotheses for the resurgence of pertussis including (in no particular order): 1) more sensitive PCR-based testing, 2) increased reporting, 3) bacterial evolution, 4) differences in the type of TH immune response induced by aP vaccination compared to wP or natural infection, and 5) lack of duration of the aP vaccine-induced immune response [3, 14,15,16,17,18]
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