tetano
Editor, Senior Moderator
Front Immunol
. 2024 Feb 28:15:1329805.
doi: 10.3389/fimmu.2024.1329805. eCollection 2024. Gonadal androgens are associated with decreased type I interferon production by plasmacytoid dendritic cells and increased IgG titres to BNT162b2 following co-vaccination with live attenuated influenza vaccine in adolescents
Oliver L Sampson[SUP] 1 [/SUP], Cecilia Jay[SUP] 1 [/SUP], Emily Adland[SUP] 1 [/SUP], Anna Csala[SUP] 1 [/SUP], Nicholas Lim[SUP] 1 [/SUP], Stella M Ebbrecht[SUP] 2 [/SUP], Lorna C Gilligan[SUP] 3 [/SUP], Angela E Taylor[SUP] 3 [/SUP], Sherley Sherafin George[SUP] 4 [/SUP], Stephanie Longet[SUP] 5 [/SUP], Lucy C Jones[SUP] 6 [/SUP], Ellie Barnes[SUP] 1 [/SUP], John Frater[SUP] 1 [/SUP], Paul Klenerman[SUP] 1 [/SUP], Susie Dunachie[SUP] 1 [/SUP], Miles Carrol[SUP] 5 [/SUP], James Hawley[SUP] 4 [/SUP], Wiebke Arlt[SUP] 3 7 [/SUP], Andreas Groll[SUP] 2 [/SUP], Philip Goulder[SUP] 1 [/SUP]
Affiliations
mRNA vaccine technologies introduced following the SARS-CoV-2 pandemic have highlighted the need to better understand the interaction of adjuvants and the early innate immune response. Type I interferon (IFN-I) is an integral part of this early innate response that primes several components of the adaptive immune response. Women are widely reported to respond better than men to tri- and quadrivalent influenza vaccines. Plasmacytoid dendritic cells (pDCs) are the primary cell type responsible for IFN-I production, and female pDCs produce more IFN-I than male pDCs since the upstream pattern recognition receptor Toll-like receptor 7 (TLR7) is encoded by X chromosome and is biallelically expressed by up to 30% of female immune cells. Additionally, the TLR7 promoter contains several putative androgen response elements, and androgens have been reported to suppress pDC IFN-I in vitro. Unexpectedly, therefore, we recently observed that male adolescents mount stronger antibody responses to the Pfizer BNT162b2 mRNA vaccine than female adolescents after controlling for natural SARS-CoV-2 infection. We here examined pDC behaviour in this same cohort to determine the impact of IFN-I on anti-spike and anti-receptor-binding domain IgG titres to BNT162b2. Through flow cytometry and least absolute shrinkage and selection operator (LASSO) modelling, we determined that serum-free testosterone was associated with reduced pDC IFN-I, but contrary to the well-described immunosuppressive role for androgens, the most bioactive androgen dihydrotestosterone was associated with increased IgG titres to BNT162b2. Also unexpectedly, we observed that co-vaccination with live attenuated influenza vaccine boosted the magnitude of IgG responses to BNT162b2. Together, these data support a model where systemic IFN-I increases vaccine-mediated immune responses, yet for vaccines with intracellular stages, modulation of the local IFN-I response may alter antigen longevity and consequently improve vaccine-driven immunity.
Keywords: adolescent vaccination; androgen; immune sex difference; plasmacytoid dendritic cell; type I interferon.
. 2024 Feb 28:15:1329805.
doi: 10.3389/fimmu.2024.1329805. eCollection 2024. Gonadal androgens are associated with decreased type I interferon production by plasmacytoid dendritic cells and increased IgG titres to BNT162b2 following co-vaccination with live attenuated influenza vaccine in adolescents
Oliver L Sampson[SUP] 1 [/SUP], Cecilia Jay[SUP] 1 [/SUP], Emily Adland[SUP] 1 [/SUP], Anna Csala[SUP] 1 [/SUP], Nicholas Lim[SUP] 1 [/SUP], Stella M Ebbrecht[SUP] 2 [/SUP], Lorna C Gilligan[SUP] 3 [/SUP], Angela E Taylor[SUP] 3 [/SUP], Sherley Sherafin George[SUP] 4 [/SUP], Stephanie Longet[SUP] 5 [/SUP], Lucy C Jones[SUP] 6 [/SUP], Ellie Barnes[SUP] 1 [/SUP], John Frater[SUP] 1 [/SUP], Paul Klenerman[SUP] 1 [/SUP], Susie Dunachie[SUP] 1 [/SUP], Miles Carrol[SUP] 5 [/SUP], James Hawley[SUP] 4 [/SUP], Wiebke Arlt[SUP] 3 7 [/SUP], Andreas Groll[SUP] 2 [/SUP], Philip Goulder[SUP] 1 [/SUP]
Affiliations
- PMID: 38481993
- PMCID: PMC10933029
- DOI: 10.3389/fimmu.2024.1329805
mRNA vaccine technologies introduced following the SARS-CoV-2 pandemic have highlighted the need to better understand the interaction of adjuvants and the early innate immune response. Type I interferon (IFN-I) is an integral part of this early innate response that primes several components of the adaptive immune response. Women are widely reported to respond better than men to tri- and quadrivalent influenza vaccines. Plasmacytoid dendritic cells (pDCs) are the primary cell type responsible for IFN-I production, and female pDCs produce more IFN-I than male pDCs since the upstream pattern recognition receptor Toll-like receptor 7 (TLR7) is encoded by X chromosome and is biallelically expressed by up to 30% of female immune cells. Additionally, the TLR7 promoter contains several putative androgen response elements, and androgens have been reported to suppress pDC IFN-I in vitro. Unexpectedly, therefore, we recently observed that male adolescents mount stronger antibody responses to the Pfizer BNT162b2 mRNA vaccine than female adolescents after controlling for natural SARS-CoV-2 infection. We here examined pDC behaviour in this same cohort to determine the impact of IFN-I on anti-spike and anti-receptor-binding domain IgG titres to BNT162b2. Through flow cytometry and least absolute shrinkage and selection operator (LASSO) modelling, we determined that serum-free testosterone was associated with reduced pDC IFN-I, but contrary to the well-described immunosuppressive role for androgens, the most bioactive androgen dihydrotestosterone was associated with increased IgG titres to BNT162b2. Also unexpectedly, we observed that co-vaccination with live attenuated influenza vaccine boosted the magnitude of IgG responses to BNT162b2. Together, these data support a model where systemic IFN-I increases vaccine-mediated immune responses, yet for vaccines with intracellular stages, modulation of the local IFN-I response may alter antigen longevity and consequently improve vaccine-driven immunity.
Keywords: adolescent vaccination; androgen; immune sex difference; plasmacytoid dendritic cell; type I interferon.