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Increasing FIM2/3 antigen-content improves efficacy of Bordetella pertussis vaccines in mice in vivo without altering vaccine-induced human reactogenicity biomarkers in vitro

Queenan, Anne Marie, Dowling, David J., Cheng, Wing Ki, Faé, Kellen, Fernandez, Jeffrey, Flynn, Peter J., Joshi, Sweta, Brightman, Spencer E., Ramirez, Juan, Serroyen, Jan, Wiertsema, Selma, Fortanier, Alexandre, van den Dobbelsteen, Germie, Levy, Ofer, Poolman, Jan
Vaccine 2019 v.37 no.1 pp. 80-89
Bordetella pertussis, adults, biomarkers, blood, chemokines, dose response, fimbriae, humans, lungs, mice, models, neonates, prostaglandins, proteins, vaccines
Current acellular-pertussis (aP) vaccines appear inadequate for long-term pertussis control because of short-lived efficacy and the increasing prevalence of pertactin-negative isolates which may negatively impact vaccine efficacy. In this study, we added fimbriae (FIM)2 and FIM3 protein to licensed 2-, 3- or 5-component aP vaccines (Pentavac®, Boostrix®, Adacel®, respectively) to assess whether an aP vaccine with enhanced FIM content demonstrates enhanced efficacy. Vaccine-induced protection was assessed in an intranasal mouse challenge model. In addition, potential reactogenicity was measured by biomarkers in a human whole blood assay (WBA) in vitro and benchmarked the responses against licensed whole cell pertussis (wP) and aP vaccines including Easyfive®, Pentavac® and Pentacel®. The results show that commercial vaccines demonstrated reduced efficacy against pertactin-negative versus pertactin-positive strains. However, addition of higher amounts of FIM2/3 to aP vaccines reduced lung colonization and increased vaccine efficacy against a pertactin-negative strain in a dose-dependent manner. Improvements in efficacy were similar for FIM2 and FIM3-expressing strains. Increasing the amount of FIM2/3 proteins in aP formulations did not alter vaccine-induced biomarkers of potential reactogenicity including prostaglandin E2, cytokines and chemokines in human newborn cord and adult peripheral blood tested in vitro. These results suggest that increasing the quantity of FIM proteins in current pertussis vaccine formulations may further enhance vaccine efficacy against B. pertussis infection without increasing the reactogenicity of the vaccine.