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seX & whY


Aug 3, 2021

Show Notes for Episode Nineteen of seX & whY: About Vaccine Research

Host: Jeannette Wolfe
Guests:

  • Christine Dahlke, Biologist and vaccine researcher at University Medical Center Hamburg-Eppendor and The German Center for Infection Research
  • Marylyn M Addo, Physician, Professor, Infectious disease specialist and vaccine researcher from University Medical Center Hamburg-Eppendor and The German Center for Infection Research

Link to their paper: Sex Differences in Immunity: Implications for the Development of Novel Vaccines Against Emerging Pathogens

Take-home points

  • Vaccine development has evolved over the years from having each vaccine be independently developed “one drug for one bug” to “plug and play” platform technology in which a vector that predictably and effectively triggers the immune system is attached to a new pathogen’s antigen (or mRNA or DNA that codes for that antigen), allowing for a much more accelerated development of new vaccines because researchers are not starting from scratch every time.
  • Researchers often test antibody levels to determine vaccine efficacy but, immunization changes other aspects of the immune system such as t cell response and some innate immunity too. These changes may be more difficult to test but may also be important for long term protection even if antibody levels fall.
  • Traditionally, drug companies have not been all that excited about developing vaccines due to the lack of a profit margin compared to a drug someone needs to take every day. The Coalition for Epidemic Preparedness Innovation (CEPI) helped jump start vaccine development in 2017 (apparently this was sparked by the realization that Ebola could have become a global pandemic and that we needed more tools to develop rapid turn- around vaccines.)
  • Sex differences - due to sex hormones and chromosomes - influence how a body’s innate and adaptative immune system works. Women generally having an advantage in fighting off infection by having a more robust innate and adaptative immune system. This may come at a cost of increased risk for autoimmune disease and in Covid, women are also much more likely to have long haul Covid symptoms. Age can act as an additional confounder with males having more impaired antibody response and increased innate inflammatory responses with age
  • Most immune cells have sex steroid receptors on them
  • Many genes that influence the immune system are housed on the X chromosome and some of them like Toll-like receptor 7 - aka the Paul Revere of the early immune response, may not undergo X-inactivation leading to it’s over expression in females and possibly giving them an advantage in decreasing their viral load compared to males after similar exposures.

Other references:

Paper referred in podcast about Dr Klein: Bishof E, Wolfe J, Klein S - Clinical trials for COVID-19 should include sex as a variable.

Podcast from last summer with my interview with Evelyn Bishof and Sabra Klein about Sex Differences in Immunology and Drug Therapy

Herpes vaccine trial showing efficacy in females and not in males.

Here are some videos on the immune system: