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This Week in Virology Episode 1309

1:46:24 recording · AUTO · 4 speakers

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Brief overview

Two papers: HPV vaccines uniquely block infection, while severe viral pneumonia primes neutrophils that accelerate lung cancer.

  1. HPV vaccine may be the only one preventing infectionVincent says that after reading the literature he concluded it is the only vaccine that prevents infection, not just disease.
  2. Slow HPV entry gives antibodies an unusual windowBinding, furin cleavage and conformational changes take hours, so neutralization still works 18 hours after the virus has attached.
  3. Severe viral pneumonia leaves a pro-tumor lungPrior severe COVID or influenza reprograms lung-resident neutrophils to Siglec-F-high, and vaccination prevents that in mice.
Executive Summary AI
  • Vincent Racaniello takes up a paper in NPJ Vaccines, "Post-Attachment Neutralization of HPV-16 by Antibodies Derived from Gardasil Vaccinated Women", first author Patricia Day and senior author John Schiller, from the National Cancer Institute at NIH with Emory and the Fred Hutchinson Cancer Center, because listeners kept asking why the HPV vaccine is called sterilizing.10:12
  • The panel explains that HPV has to reach the basal keratinocytes through a break in the mucosa, attach to heparin sulfate proteoglycans on the basement membrane, expose L2, be cleaved by furin and change conformation again before entry — a process that takes hours and leaves a long window for antibodies.18:11
  • Using HACAT keratinocytes, sera from Gardasil-vaccinated women and 13 monoclonals from memory B cells, the team still saw inhibition of infectivity 18 hours after attachment, by three mechanisms — retention at the cell surface, antibody-induced shedding, and degradation inside the cell that is not TRIM21-mediated — and the same mechanisms showed up in polyclonal serum.23:54
  • The second paper, published in Cell, "Respiratory viral infections prime accelerated lung cancer growth", has co-first authors Wei Qian and Zhao-Qin Wei and senior author Ji Sun, with teams from the University of Virginia, the University of Pittsburgh, the Mayo Clinic in Jacksonville and Cedars-Sinai.43:40
  • In Epic Cosmos records starting from 75.9 million adults, prior severe COVID-19 carried a 1.24-fold higher lung cancer hazard, and mouse work traced it to Siglec-F-high lung-resident neutrophils driven by G-CSF and TGF-beta — with vaccination, neutrophil blockade and anti-PD-L1 all reducing tumor burden.52:55
Key Quote
“it is, it is the only vaccine that prevents infection.”
— Vincent Racaniello12:02
Key Quote
“So this is, I think we've mentioned this before, This is vaccinologists fooling Mother Nature.”
— Rich Condit41:19
Key Quote
“So neutrophils are innate immune cells that basically largely work by phagocytosis.”
— Breanne Barker49:06