Vaccine-Induced Cellular Immunity against Bordetella pertussis: Harnessing Lessons from Animal and Human Studies to Improve Design and Testing of Novel Pertussis Vaccines

Abstract

Pertussis ('whooping cough') is a severe respiratory tract infection that primarily affects young children and unimmunised infants. Despite widespread vaccine coverage, it remains one of the least well-controlled vaccine-preventable diseases, with a recent resurgence even in highly vaccinated populations. Although the exact underlying reasons are still not clear, emerging evidence suggests that a key factor is the replacement of the whole-cell (wP) by the acellular pertussis (aP) vaccine, which is less reactogenic but may induce suboptimal and waning immunity. Differences between vaccines are hypothesised to be cell-mediated, with polarisation of Th1/Th2/Th17 responses determined by the composition of the pertussis vaccine given in infancy. Moreover, aP vaccines elicit strong antibody responses but fail to protect against nasal colonisation and/or transmission, in animal models, thereby potentially leading to inadequate herd immunity. Our review summarises current knowledge on vaccine-induced cellular immune responses, based on mucosal and systemic data collected within experimental animal and human vaccine studies. In addition, we describe key factors that may influence cell-mediated immunity and how antigen-specific responses are measured quantitatively and qualitatively, at both cellular and molecular levels. Finally, we discuss how we can harness this emerging knowledge and novel tools to inform the design and testing of the next generation of improved infant pertussis vaccines.

Keywords: B-cells; Bordetella pertussis; T-cells; antigen-specific; colonisation; correlate-of-protection; epitope; immunity; vaccination; whooping cough.

Figure 1

Schematic summary of the hypothesised immunological differences between the two infant pertussis vaccines, including their impact on: (a) protection against pertussis infection and disease; (b) longevity of protection. Shown are systemic T-helper cell responses induced by the whole-cell pertussis infant vaccine and how they might compare to acellular pertussis immunisation (indicated by white arrows); proposed mechanisms are antibody/B-cell dependent and independent. Ig, immunoglobulin; Th, T-helper; Tfh, T-follicular helper; Treg, T-regulatory; TRM, tissue-resident memory cells.

Figure 1

Schematic summary of the hypothesised immunological differences between the two infant pertussis vaccines, including their impact on: (a) protection against pertussis infection and disease; (b) longevity of protection. Shown are systemic T-helper cell responses induced by the whole-cell pertussis infant vaccine and how they might compare to acellular pertussis immunisation (indicated by white arrows); proposed mechanisms are antibody/B-cell dependent and independent. Ig, immunoglobulin; Th, T-helper; Tfh, T-follicular helper; Treg, T-regulatory; TRM, tissue-resident memory cells.

Figure 2

Schematic summary of future research priorities to characterise the differences between acellular and whole-cell pertussis vaccines, ultimately aiming to improve the design and testing of longer-lasting and more effective next-generation pertussis immunisations. Key gaps in knowledge are outlined which shape our understanding of differences in either vaccine-mediated immunity or vaccine content, both of which are interdependent and interacting. aP, acellular pertussis; Bp, Bordetella pertussis; LLPC, long-lived plasma cell; LOS, lipooligosaccharide; Th, T-helper; TLR, Toll-like receptor; TRM, tissue-resident memory; wP, whole-cell pertussis.