Acellular Pertussis Vaccines Induce Anti-pertactin Bactericidal Antibodies Which Drives the Emergence of Pertactin-Negative Strains.

Elodie Lesne,Frances Alexander,Stephen Taylor,Breeze E Cavell,Cécile A C M Van Els,Andrew Gorringe,Mary Matheson,Ruby Persaud,Irene Freire-Martin

doi:10.3389/fmicb.2020.02108

Abstract

Despite high vaccination coverage, Bordetella pertussis the causative agent of whooping cough is still a health concern worldwide. A resurgence of pertussis cases has been reported, particularly in countries using acellular vaccines with waning immunity and pathogen adaptation thought to be responsible. A better understanding of protective immune responses is needed for the development of improved vaccines. In our study, B. pertussis strain B1917 variants presenting a single gene deletion were generated to analyze the role of vaccine components or candidate vaccine antigens as targets for bactericidal antibodies generated after acellular vaccination or natural infection. Our results show that acellular vaccination generates bactericidal antibodies that are only directed against pertactin. Serum bactericidal assay performed with convalescent samples show that disease induces bactericidal antibodies against Prn but against other antigen(s) as well. Four candidate vaccine antigens (CyaA, Vag8, BrkA, and TcfA) have been studied but were not targets for complement-mediated bactericidal antibodies after natural infection. We confirm that Vag8 and BrkA are involved in complement resistance and would be targeted by blocking antibodies. Our study suggests that the emergence and the widespread circulation of Prn-deficient strains is driven by acellular vaccination and the generation of bactericidal antibodies targeting Prn.

Highlights

Bordetella pertussis, the causative agent of whooping cough, is a gram-negative bacterium that colonizes the human respiratory tract
To determine the importance of B. pertussis aP vaccine antigens for antibody and complement-dependent killing of B. pertussis, single deletions of the entire gene of fhaB, ptxABDEC, fim3, and prn were performed in the B1917 background by homologous recombination
The low fluorescence intensity values obtained with the anti-FHA and anti-PTX monoclonal antibodies (Figure 1A, middle panels) can be explained by the low amount of FHA and PTX expressed at the surface of washed bacteria as these antigens are mainly secreted

Summary

Introduction

Bordetella pertussis, the causative agent of whooping cough, is a gram-negative bacterium that colonizes the human respiratory tract. In the last two decades, the incidence of pertussis has been increasing in several countries which have high aP vaccine coverage (Nieves and Heininger, 2016; Pinto and Merkel, 2017; Esposito et al, 2019). This is likely to be caused by a number of factors including a shorter duration of protection provided by aP than wP vaccines (Witt et al, 2013; Klein et al, 2016), a greater circulation of B. pertussis in aP-vaccinated populations (Althouse and Scarpino, 2015) and evolution of strains with greater fitness (Belcher and Preston, 2015). Pertactin-deficient strains are by far the most commonly reported and in some countries using aP vaccination, the prevalence has reached around 80% (Lam et al, 2014; Martin et al, 2015)

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Conclusion