A system-view of Bordetella pertussis booster vaccine responses in adults primed with whole-cell versus acellular vaccine in infancy.

Ricardo Da Silva Antunes,Lisa A Purcell,Richard H Scheuermann,Natalie Khalil,Bali Pulendran,Bjoern Peters,Jason Bennett,Mikhail Pomaznoy,Adrienne P Gilkes,Ferran Soldevila,Christopher D Petro,Yu Qian,Aishwarya Mandava,Mario Cortese,Alessandro Sette,Mariana Babor,Yuan Tian

doi:10.1172/jci.insight.141023

Abstract

The increased incidence of whooping cough worldwide suggests that current vaccination against Bordetella pertussis infection has limitations in quality and duration of protection. The resurgence of infection has been linked to the introduction of acellular vaccines (aP), which have an improved safety profile compared with the previously used whole-cell (wP) vaccines. To determine immunological differences between aP and wP priming in infancy, we performed a systems approach of the immune response to booster vaccination. Transcriptomic, proteomic, cytometric, and serologic profiling revealed multiple shared immune responses with different kinetics across cohorts, including an increase of blood monocyte frequencies and strong antigen-specific IgG responses. Additionally, we found a prominent subset of aP-primed individuals (30%) with a strong differential signature, including higher levels of expression for CCL3, NFKBIA, and ICAM1. Contrary to the wP individuals, this subset displayed increased PT-specific IgE responses after boost and higher antigen-specific IgG4 and IgG3 antibodies against FHA and FIM2/3 at baseline and after boost. Overall, the results show that, while broad immune response patterns to Tdap boost overlap between aP- and wP-primed individuals, a subset of aP-primed individuals present a divergent response. These findings provide candidate targets to study the causes and correlates of waning immunity after aP vaccination.

Highlights

A Bordetella pertussis vaccine containing heat-killed, whole-cell bacteria was developed in the first 2 decades of the 20th century, following the isolation of the organism in 1906 [1]
The recruited individuals were eligible for booster vaccinations with Tdap, containing tetanus toxoid (T), diphtheria toxoid (d), and acellular Pertussis antigens
We aimed to utilize multisystem profiling of immunological response to Tdap booster vaccination in wP- and acellular Pertussis (aP)-primed individuals to uncover immune signatures of the booster immunization that are shared across individuals, as well as those that differ based on the type of the priming vaccine

Summary

Introduction

A Bordetella pertussis vaccine containing heat-killed, whole-cell bacteria was developed in the first 2 decades of the 20th century, following the isolation of the organism in 1906 [1]. After decades of research and improvements, the vaccine was put into routine use in the mid-20th century and has, since demonstrated its efficacy to confer immunity against the pathogen [1,2,3,4]. This vaccine was administered in a mix with toxoid antigens derived from the causative agents of diphtheria and tetanus called DTwP. T cell phenotype and polarization differed, and those differences persisted decades after the vaccine priming [25,26,27]; this difference has been suggested to be linked with dissimilar vaccine efficacy and immune imprinting [27,28,29,30]

Objectives

Methods

Results

Conclusion