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Systems Vaccinology & Human Immune Variation

29:42 recording · AUTO · 2 speakers

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Brief overview

Bali Palundren explains how systems vaccinology reads the human immune system, revealing microbiome effects and durability mechanisms.

  1. Mouse models mislead in the detailsVaccines and drugs that work beautifully well in mice often simply do not translate into humans, because small differences matter like missing spokes on a wheel.
  2. A vaccine is a controlled human experimentPalundren calls vaccination a beautifully synchronized perturbation of the immune system, safely administered, with 27 licensed vaccines engaging different innate pathways.
  3. Observation can lead, but hypothesis must followGalileo's four moons of Jupiter and Darwin's notes on beak curvature began without hypotheses, yet observation alone is only a starting point.
Executive Summary AI
  • Cindy Leifer records this special Immune booster on May 5th 2025 at the American Association of Immunologists annual conference in Honolulu, Hawaii, with Bali Palundren, the Violetta L. Horton Professor and Director of the Institute for Immunity, Transplantation, and Infection at Stanford Medicine.0:00
  • Palundren says a year off before Cambridge, spent at the International Center for Diarrheal Disease Research in Bangladesh where his father worked with the United Nations, ended his plan to become an astronomer and turned him to vaccine science.3:23
  • After a PhD with Sir Gustav Nossel at the Walter and Eliza Hall Institute, he took a non-traditional postdoc at the small Seattle biotech Immunex in the mid-90s, working on Flt3 ligand, the first growth factor for dendritic cells, then spent almost three years at the Baylor Institute for Immunology Research showing it expands dendritic cells in humans, before Rafi Ahmed recruited him to the Emory6:11
  • Systems vaccinology there first produced blood signatures that predicted T cell and antibody responses, then mechanism: the microbiome shapes vaccine antibody responses, tested in humans given vancomycin, neomycin and metronidazole that cut bacteria 10,000-fold, and a paper published a couple of months ago showed megakaryocytes in the bone marrow give plasma cells survival signals that extend dura15:24
  • He names human diversity as the next frontier, since this roughly 15-year-old revival has mostly studied healthy adults in high-income countries, and asks why the human immune system appears more resilient than that of mice, from which we diverged 100 million years ago.22:25
Key Quote
“Okay, exaggerate. Exactly. What is it? Mice exaggerate, monkeys lie or something like that.”
— Cindy Leifer1:32
Key Quote
“I'm always reminded of the Big Bang when the first antigen or first virus comes in. It is this Big Bang, just like how the universe began and how it evolves.”
— Bali Palundren4:28
Key Quote
“But also, what we discovered was that many, many vaccines and medicines and drugs that work beautifully well in mice simply do not translate into humans.”
— Bali Palundren12:17