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.

Immunogenicity of a Candidate DTacP-sIPV Combined Vaccine and Its Protection Efficacy against Pertussis in a Rhesus Macaque Model

“…These results suggest that though all the vaccination groups could effectively prevent the colonization of pertussis, the number of pertussis colonies in the wP group was significantly lower than that in the aP-related groups and that the clearance of pertussis infection was significantly earlier than that in the aP and negative control groups. Thus, wP was better at preventing pertussis infection than the aP vaccine [23,25].…”

Memory B Cell Activation Induced by Pertussis Booster Vaccination in Four Age Groups of Three Countries

“…Also stronger Th2 responses were reported in aP primed versus wP primed individuals ( 37 ). Stronger Th2 responses in aP primed individuals have been described often, in young children as well as in adolescents ( 38 ). Therefore, age difference does not seem to explain why aP primed young children have better B cell responses following an aP booster while in adolescence wP primed individuals have higher frequencies.…”

Modulation of Inflammatory Signaling Molecules in Bordetella pertussis Antigen-Challenged Human Monocytes in Presence of Adrenergic Agonists

“…Despite widespread vaccination with the current acellular pertussis (aP) vaccine Tdap, pertussis infection (whooping cough) is currently re-emerging as a major health risk among well-vaccinated populations [47][48][49], most likely due to the fading of vaccine-induced protective immunity [4]. This pertussis scenario asks for more fundamental research on vaccine immunology for a better understanding of the vaccine antigen-induced immune response, its long-term persistence, and its correlation with long-lasting protection against infection to design next-generation pertussis vaccines with a longer duration of protection.…”