1. System vaccinology analysis of predictors and mechanisms of antibody response durability to multiple vaccines in humans.
- Author
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Cortese M, Hagan T, Rouphael N, Wu SY, Xie X, Kazmin D, Wimmers F, Gupta S, van der Most R, Coccia M, Aranuchalam PS, Nakaya HI, Wang Y, Coyle E, Horiuchi S, Wu H, Bower M, Mehta A, Gunthel C, Bosinger SE, Kotliarov Y, Cheung F, Schwartzberg PL, Germain RN, Tsang J, Li S, Albrecht R, Ueno H, Subramaniam S, Mulligan MJ, Khurana S, Golding H, and Pulendran B more...
- Subjects
- Humans, Vaccinology methods, Megakaryocytes immunology, Blood Platelets immunology, Influenza, Human immunology, Influenza, Human prevention & control, Female, Plasma Cells immunology, Adult, Male, Adjuvants, Immunologic, Influenza Vaccines immunology, Antibody Formation immunology, Antibodies, Viral immunology, Antibodies, Viral blood
- Abstract
We performed a systems vaccinology analysis to investigate immune responses in humans to an H5N1 influenza vaccine, with and without the AS03 adjuvant, to identify factors influencing antibody response magnitude and durability. Our findings revealed a platelet and adhesion-related blood transcriptional signature on day 7 that predicted the longevity of the antibody response, suggesting a potential role for platelets in modulating antibody response durability. As platelets originate from megakaryocytes, we explored the effect of thrombopoietin (TPO)-mediated megakaryocyte activation on antibody response longevity. We found that TPO administration enhanced the durability of vaccine-induced antibody responses. TPO-activated megakaryocytes also promoted survival of human bone-marrow plasma cells through integrin β1/β2-mediated cell-cell interactions, along with survival factors APRIL and the MIF-CD74 axis. Using machine learning, we developed a classifier based on this platelet-associated signature, which predicted antibody response longevity across six vaccines from seven independent trials, highlighting a conserved mechanism for vaccine durability., Competing Interests: Competing interests: R.v.d.M., M. Cortese and M. Coccia are or were employees of GSK. B.P. serves or has served on the External Immunology Board of GSK and on the Scientific Advisory Board of Sanofi, Medicago, Boehringer Ingelheim, Pharmajet, Icosavax, Imu Biosciences and Ed-Jen, and holds shares at CircBio and Orbital Therapeutics. R.v.d.M. and T.H. hold shares in the GSK group of companies. The other authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature America, Inc.) more...
- Published
- 2025
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