System vaccinology analysis of predictors and mechanisms of antibody response durability to multiple vaccines in humans.
Document Type
Article
Publication Date
1-1-2025
Original Citation
Cortese M,
Hagan T,
Rouphael N,
Wu S,
Xie X,
Kazmin D,
Wimmers F,
Gupta S,
van der Most R,
Coccia M,
Aranuchalam P,
Nakaya H,
Wang Y,
Coyle E,
Horiuchi S,
Wu H,
Bower M,
Mehta A,
Gunthel C,
Bosinger S,
Kotliarov Y,
Cheung F,
Schwartzberg P,
Germain R,
Tsang J,
Li S,
Albrecht R,
Ueno H,
Subramaniam S,
Mulligan M,
Khurana S,
Golding H,
Pulendran B.
System vaccinology analysis of predictors and mechanisms of antibody response durability to multiple vaccines in humans. Nat Immunol. 2025;26(1):116-30.
Keywords
JGM, Humans, Influenza Vaccines, Antibody Formation, Antibodies, Viral, Vaccinology, Megakaryocytes, Blood Platelets, Influenza, Human, Female, Plasma Cells, Adult, Male, Adjuvants, Immunologic
JAX Source
Nat Immunol. 2025;26(1):116-30.
ISSN
1529-2916
PMID
39747435
DOI
https://doi.org/10.1038/s41590-024-02036-z
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.