Abstract
The immune response elicited by the protective whole-cell pertussis (wP) versus the less-protective acellular pertussis (aP) vaccine has been well characterized; however, important clinical problems remain unsolved, as the inability of the currently administered aP vaccine is resulting in the reemergence of clinical disease (i.e., whooping cough). Strong evidence has shown that original, childhood aP and wP priming vaccines provide a long-lasting imprint on the CD4+ T cells that impacts protective immunity. However, aP vaccination might prevent disease but not infection, which might also affect the breadth of responses to Bordetella pertussis (BP) antigens. Thus, characterizing and defining novel targets associated with T cell reactivity are of considerable interest. Here, we compare the T cell reactivity of original aP and wP priming for different antigens contained or not contained in the aP vaccine and define the basis of a full-scale genomic map of memory T cell reactivity to BP antigens in humans. Our data show that the original priming after birth with aP vaccines has higher T cell reactivity than originally expected against a variety of BP antigens and that the genome-wide mapping of BP using an ex vivo screening methodology is feasible, unbiased, and reproducible. This could provide invaluable knowledge towards the direction of a new and improved pertussis vaccine design.
Highlights
Several studies and epidemiological evidence suggest that the immunity induced by Bordetella pertussis (BP) acellular vaccines wanes more rapidly as compared to the immunity elicited by vaccines based on whole BP cells [1,2,3,4,5,6,7,8]
These studies were enabled by the definition of the T cell epitopes contained in the BP antigens contained in the acellular pertussis (aP) vaccines, which was achieved following the systematic analysis of responses following the expansion of antigen-specific T cells in short-term in vitro culture [9], and the development of the activation-induced marker (AIM) assays, which allowed measurement of responses directly ex vivo without any further manipulation [11, 12]
We measured responses against a pool of BP epitopes from the adenylate cyclase toxin (ACT) antigen, a virulence factor that is not contained in the aP vaccine [39]
Summary
Several studies and epidemiological evidence suggest that the immunity induced by Bordetella pertussis (BP) acellular vaccines (aP) wanes more rapidly as compared to the immunity elicited by vaccines based on whole BP cells (wP) [1,2,3,4,5,6,7,8]. In previous studies [9, 10], we have investigated potential immune correlates of this waning immunity, by dissecting immune responses in young adults, originally primed with either aP or wP vaccines These studies were enabled by the definition of the T cell epitopes contained in the BP antigens contained in the aP vaccines (pertussis toxin, PtTox; two serotypes of fimbriae, Fim2/3; filamentous hemagglutinin, FHA; and pertactin, PRN), which was achieved following the systematic analysis of responses following the expansion of antigen-specific T cells in short-term in vitro culture [9], and the development of the activation-induced marker (AIM) assays, which allowed measurement of responses directly ex vivo without any further manipulation [11, 12]. These observations led to the hypothesis that lower proliferative capacity of aP might be linked to a regulatory cell population, since no difference between cohorts was noted when purified T cell subpopulations were assayed
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