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<p>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.</p>

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System vaccinology analysis of predictors and mechanisms of antibody response durability to multiple vaccines in humans

  • 期刊论文

  • 发表日期：

    2025年1月2日

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  • Mario Cortese,
  • Thomas Hagan,
  • Nadine Rouphael,
  • Sheng-Yang Wu,
  • Xia Xie,
  • Dmitri Kazmin,
  • Florian Wimmers,
  • Shakti Gupta,
  • Robbert van der Most,
  • Margherita Coccia,
  • Prabhu S. Aranuchalam,
  • Helder I. Nakaya,
  • Yating Wang,
  • Elizabeth Coyle,
  • Shu Horiuchi,
  • Hanchih Wu,
  • Mary Bower,
  • Aneesh Mehta,
  • Clifford Gunthel,
  • Steve E. Bosinger,
  • Yuri Kotliarov,
  • Foo Cheung,
  • Pamela L. Schwartzberg,
  • Ronald N. Germain,
  • John Tsang,
  • Shuzhao Li,
  • Randy Albrecht,
  • Hideki Ueno,
  • Shankar Subramaniam,
  • Mark J. Mulligan,
  • Surender Khurana,
  • Hana Golding,
  • Bali Pulendran

摘要

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.