Publicação

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

Detalhes bibliográficos
Resumo:	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.
Autores principais:	Gillard, Joshua
Outros Autores:	Suffiotti, Madeleine; Brazda, Peter; Venkatasubramanian, Prashanna B.; Versteegen, Pauline; Jonge, Marien I. de; Kelly, Dominic; Bibi, Sagida; Pinto, Marta Valente; Simonetti, Elles; Babiceanu, Mihaela; Kettring, Andrew; Teodosio, Cristina; Groot, Ronald de; Berbers, Guy; Stunnenberg, Hendrik G.; Schanen, Brian; Fenwick, Craig; Huynen, Martijn A.; Diavatopoulos, Dimitri A.
Assunto:	vaccination persistent humoral immunity Bordetella pertussis
Ano:	2024
País:	Portugal
Tipo de documento:	contribuição para revista
Tipo de acesso:	acesso aberto
Instituição associada:	Egas Moniz - Cooperativa de Ensino Superior, CRL
Idioma:	inglês
Origem:	Egas Moniz - Cooperativa de Ensino Superior, CRL

Descrição
Resumo:	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.