Dissecting Sex Differences in the Immune Response to Vaccines

Vaccines represent one of the most impactful public health interventions with the prevention of millions of infections and deaths annually worldwide. As illustrated by recent epidemic or pandemic outbreaks caused by emerging viruses such as Ebola Virus, MERS-CoV and more recently SARS-CoV-2, the need for rapid and strategic vaccine development remains paramount. Men and women differ in the immune response to vaccination with females typically developing higher antibody responses, but also experiencing more adverse reactions following vaccination than males. Yet the exact mechanisms and signaling pathways involved in the differential vaccine outcomes between the sexes remain incompletely understood. We hypothesize that: a) sex hormones regulate critical innate signaling pathways resulting in differential outcomes in vaccine reactogenicity and immunogenicity and b) gene-dosage effects resulting from escape from X-chromosome inactivation (XCI) contribute to sex-specific differences in vaccine responses. These hypotheses will be explored using data and biomaterial from two unique Phase 1 clinical trials investigating novel emergency vaccines. We propose to prospectively investigate and dissect sex-specificity in immunity to vaccines against two important emerging respiratory pathogens with pandemic potential and high global significance: MERS-CoV and SARS-CoV-2, two recently discovered novel coronaviruses. A detailed understanding of the molecular factors associated with sex-differences in vaccine-induced immune responses may ultimately allow for strategic modulation of vaccine immunity and foster individualized vaccine design.

Beisel C, Jordan-Paiz A, Köllmann S, Ahrenstorf AE, Padoan B, Barkhausen T, Addo MM, Altfeld M. (2023)
Sex differences in the percentage of IRF5 positive B cells are associated with higher production of TNF-α in women in response to TLR9 in humans
Biology of Sex Differences 14:11

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Anahita Fathi, Marylyn M Addo, Christine Dahlke. (2021)
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Front Immunol 11:601170

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Koch T, Dahlke C, Fathi A, Kupke A, Krähling V, Okba MA, Halwe S, Rohde C, Eickmann M, Volz A, Hesterkamp T, Jambrecina A, Borregaard S, Ly ML, Zinser ME, Bartels E, Poetsch J, Neumann R, Fux R, Schmiedel S, Lohse AW, Haagmans BL, Sutter G, Becker S, Addo MM. (2020)
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Lancet Infect Dis 20:827-838

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Heidepriem J, Krähling V, Dahlke C, Wolf T, Klein F, Addo MM*, Becker S*, Loeffler F*. (2020)
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Biotechnol J 15:e2000069

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Friedrich SK, Schmitz R, Bergerhausen M, Lang J, Cham LB, Duhan V, Häussinger D, Hardt C, Addo M, Prinz M, Asano K, Lang PA, Lang KS. (2020)
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Vaccines (Basel). 8(1):E142

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Ehrhardt S A, Zehner M, Krähling V, Cohen-Dvashi H, Kreer C, Elad N, Gruell H, Ercanoglu MS, Schommers P, Gieselmann L, Eggeling R, Dahlke C, Wolf T, Pfeifer N, Addo, MM, Diskin R, Becker S, & Klein F. (2019)
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Poetsch J.H., Dahlke C, Zinser ME, Kasonta R, Lunemann S, Rechtien A, My Linh Ly, Stubbe H.C., Krähling V, Biedenkopf N, Eickmann M, Fehling SK, Olearo F, Strecker T, Sharma P, Lang KS, Lohse AW, Schmiedel S, Becker S, VSV-Ebola Consortium (VEBCON), Addo MM. (2019)
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Rechtien A, Richert L, Lorenzo H, Martrus G, Hejblum B, Dahlke C, Kasonta R, Zinser M, Stubbe H, Matschl U, Lohse A, Krähling V, Eickmann M, Becker S; VEBCON Consortium, Thiébaut R, Altfeld M, Addo MM. (2017)
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Dahlke C, Kasonta R, Lunemann S, Krähling V, Zinser ME, Biedenkopf N, Fehling SK, Ly ML, Rechtien A, Stubbe HC, Olearo F, Borregaard S, Jambrecina A, Stahl F, Strecker T, Eickmann M, Lütgehetmann M, Spohn M, Schmiedel S, Lohse AW, Becker S, Addo MM, VEBCON Consortium. (2017)
Dose-dependent T-cell Dynamics and Cytokine Cascade Following rVSV-ZEBOV Immunization
EBioMedicine 19:107-11

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Agnandji ST, Huttner A, Zinser ME, Njuguna P, Dahlke C, Fernandes JF, Yerly S, Dayer JA, Kraehling V, Kasonta R, Adegnika AA, Altfeld M, Auderset F, Bache EB, Biedenkopf N, Borregaard S, Brosnahan JS, Burrow R, Combescure C, Desmeules J, Eickmann M, Fehling SK, Finckh A, Goncalves AR, Grobusch MP, Hooper J, Jambrecina A, Kabwende AL, Kaya G, Kimani D, Lell B, Lemaître B, Lohse AW, Massinga-Loembe M, Matthey A, Mordmüller B, Nolting A, Ogwang C, Ramharter M, Schmidt-Chanasit J, Schmiedel S, Silvera P, Stahl FR, Staines HM, Strecker T, Stubbe HC, Tsofa B, Zaki S, Fast P, Moorthy V, Kaiser L, Krishna S, Becker S, Kieny MP, Bejon P*, Kremsner PG*, Addo MM*, Siegrist CA*. (2016)
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N Engl J Med. 374:1647-60

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Addo MM, Altfeld M. (2014)
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* equal contribution