Antiviral responses induced by Tdap-IPV vaccination are associated with persistent humoral immunity to Bordetella pertussis

Joshua Gillard, Madeleine Suffiotti, Peter Brazda, Prashanna B. Venkatasubramanian, Pauline Versteegen, Marien I. de Jonge, Dominic Kelly, Sagida Bibi, Marta Valente Pinto, Elles Simonetti, Mihaela Babiceanu, Andrew Kettring, Cristina Teodosio, Ronald de Groot, Guy Berbers, Hendrik G. Stunnenberg, Brian Schanen, Craig Fenwick, Martijn A. Huynen, Dimitri A. Diavatopoulos*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Many countries continue to experience pertussis epidemics despite widespread vaccination. Waning protection after booster vaccination has highlighted the need for a better understanding of the immunological factors that promote durable protection. Here we apply systems vaccinology to investigate antibody responses in adolescents in the Netherlands (N = 14; NL) and the United Kingdom (N = 12; UK) receiving a tetanus-diphtheria-acellular pertussis-inactivated poliovirus (Tdap-IPV) vaccine. We report that early antiviral and interferon gene expression signatures in blood correlate to persistence of pertussis-specific antibody responses. Single-cell analyses of the innate response identified monocytes and myeloid dendritic cells (MoDC) as principal responders that upregulate antiviral gene expression and type-I interferon cytokine production. With public data, we show that Tdap vaccination stimulates significantly lower antiviral/type-I interferon responses than Tdap-IPV, suggesting that IPV may promote antiviral gene expression. Subsequent in vitro stimulation experiments demonstrate TLR-dependent, IPV-specific activation of the pro-inflammatory p38 MAP kinase pathway in MoDCs. Together, our data provide insights into the molecular host response to pertussis booster vaccination and demonstrate that IPV enhances innate immune activity associated with persistent, pertussis-specific antibody responses.

Original languageEnglish
Article number2133
Pages (from-to)1-17
Number of pages17
JournalNature Communications
Volume15
Issue number1
DOIs
Publication statusPublished - 8 Mar 2024

Fingerprint

Dive into the research topics of 'Antiviral responses induced by Tdap-IPV vaccination are associated with persistent humoral immunity to Bordetella pertussis'. Together they form a unique fingerprint.

Cite this