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February 4, 2021 23 mins

How do the various COVID-19 vaccines work, and when should patients be vaccinated? We tackle these topics and more in this episode.

Our host David H. Henry, MD, is joined by Drew Weissman, MD, PhD, a professor at the University of Pennsylvania, Philadelphia. Dr. Weissman codeveloped the messenger RNA (mRNA) technology being used in the COVID-19 vaccines produced by Pfizer/BioNTech and Moderna.

History of mRNA vaccines

  • Testing of mRNA vaccines began in the 1990s.
  • An initial problem with these vaccines was that the RNA was highly inflammatory.
  • Dr. Weissman and his colleague, Katalin Karikó, PhD, discovered how to fix that problem in 2005.
  • The pair found that placing modified nucleosides into mRNA made it noninflammatory and allowed for increased production of protein from the RNA – up to a 1,000-fold increase in mice.
  • This technology is the basis of the Moderna and Pfizer/BioNTech COVID-19 vaccines.

Immunology and vaccines

  • To produce a good immune response, antigen must be present for a long time, though the optimal amount of time is unknown, Dr. Weissman said.
  • The mRNA lipid nanoparticles (LNPs) used in the COVID-19 vaccines make protein for 10-14 days, resulting in a “great” immune response, according to Dr. Weissman.
  • Most vaccines have an adjuvant, or something that stimulates the immune response by inducing TH1 or TH2 responses.
  • The LNP used in the COVID-19 vaccines is an adjuvant that makes a specialized CD4 helper cell that drives antibody production, increases antibody affinity, and matures antibodies to make long-lived plasma cells to allow for long-lived antibody responses.
  • This is the only adjuvant known that induces these type of helper T cells.

COVID-19 vaccine reactions

  • Adverse reactions to COVID-19 vaccination – flu-like symptoms, arm pain, etc. – are caused by the LNP, not the spike protein.
  • Once the LNP is gone, usually within the first 24 hours, symptoms dissipate.
  • The amount of spike protein produced decreases over 14 days.
  • It’s unclear if patients should take NSAIDs to manage symptoms after COVID-19 vaccination, as this hasn’t been tested.
  • However, with influenza vaccination, taking an NSAID will decrease the immune response.

Variants and their impact on vaccination

  • SARS-CoV-2 variants have been reported in Brazil, South Africa, California, and the United Kingdom.
  • Dr. Weissman explained that there are two kinds of variation: when a virus learns how to better infect people and when the virus learns to avoid immune responses.
  • Most SARS-CoV-2 variants are equally addressed by the vaccines, though we know vaccines have reduced efficacy against the South African variant, Dr. Weissman said.
  • The good news is that coronavirus mutates very slowly, and it’s easy with mRNA vaccines to “plug in” a mutant and make a more effective vaccine, Dr. Weissman said.

Vaccinating cancer patients: Treatment considerations

For patients receiving chemotherapy:

  • We don’t know the best time to administer COVID-19 vaccines to patients on chemotherapy, as this hasn’t been studied, Dr. Weissman said.
  • When other vaccines were given to subjects receiving chemotherapy, those vaccines did not work as well.
  • Chemotherapy knocks down myeloid cells around day 7, with recovery typically around day 28.
  • Dr. Weissman said he would probably vaccinate at day 14 in the chemotherapy cycle, as the germinal centers where B cells are produced form about 2-7 days after receipt of th
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