Research must consider gender differences in vaccine responses
JTwo days after receiving my second dose of the Moderna mRNA vaccine in a clinical trial, my body was still mounting a robust immune response when, from the floor of my son’s bathroom, I frantically phoned the site. clinical research center at the University of Illinois. .
The region of my brain that controls thermoregulation, the hypothalamus, probably detected the flood of vaccine-induced viral protein copies in my bloodstream and raised my internal thermostat to 104.7 degrees F, a fever high enough to make me delirious. The trial’s principal investigator requested a prescription for anti-nausea medication and two bags of intravenous fluid, which a mobile service delivered to me at home to stabilize me.
As a volunteer in Moderna’s Covid-19 vaccine trial, I had received my second dose in early February 2021, before side effect information was well known. As I recovered over the next few days, I began to wonder if my grade 4 fever was typical or if there was something in my biology that was triggering such a dramatic immune response.
Vaccines save lives and the record time scientists have been developing Covid-19 vaccines is unprecedented. Although debilitating side effects from vaccines are rare, vaccine trials and dosage recommendations tend to ignore the growing evidence that immune responses differ significantly in men and women, both in response to viral infections and after infection. vaccination.
When I dug deeper into vaccine development, I discovered a familiar tussle in which new scientific recommendations that take biological gender disparities into account continue to clash with established practices and beliefs. .
A decade before the emergence of Covid-19, the world was facing the H1N1 pandemic. As researchers raced to create a vaccine, infectious disease researcher Sabra L. Klein posed a simple question in a New York Times opinion piece: Do women need such big flu shots? ? She defied vaccine conventions by suggesting that giving women a smaller dose of the H1N1 vaccine would be effective, while optimizing the limited supply of vaccines for the second wave of the pandemic. Klein’s recommendations did not prevail, but she is now joined by a chorus of voices within the scientific community working to reverse the gender blind spot in biomedical research and vaccine development.
Before vaccines and drugs are tested in humans, researchers study their effects in cells and in animals. The fight against gender bias begins in petri dishes and animal studies. In a February 2022 report, Irene Miguel-Aliega, professor of genetics and physiology at Imperial College London, slams the dangers of gender bias research design: is not a good reason to exclude either gender in future experiments.
A now well-known example of gender differences is the sleeping pill Ambien. It had been on the market for 20 years before the Food and Drug Administration halved the recommended dose for women in 2013. It wasn’t until women were “significantly more likely to have car accidents after one night of Ambien” that experts began to realize the gender differences, Klein told me, referring to the FDA notification that she had received about 700 reports linking Ambien and impaired driving ability. impaired and/or road accidents. It turns out that women’s livers metabolize the drug more slowly than men’s.
While the media blitz and outcry over the Ambien fallout targeted FDA regulators, federal scientists at the National Institutes of Health had previously worked to understand why new drugs failed in human trials after promising preclinical research. Some failures date back to the early stages of animal research and analysis that did not consider effects on males and females separately.
“When investigators consider sex, they often find sex differences,” Chyren Hunter, associate director of basic and translational research at the NIH Office of Women’s Health Research, told me. Hunter and his team are spreading the word about the preclinical treasure trove of data “hidden in plain sight” as early scientific research includes both genders.
Not all researchers seeking federal funding need to study sex differences, but according to a 6-year-old NIH policy, commonly referred to as SABV (sex as a biological variable), researchers must “consider how biological sex may impact the question they are studying.” The SABV is not a mandate, but a criterion, and Hunter tells the researchers that it is “not an obstacle is an opportunity”.
Sexism has deep and twisted roots that have long plagued science and medicine. Hysteria, which comes from the Greek word hystera, which means uterus, was a medical diagnosis until 1980 when it was removed from the main reference guide for mental health professionals. Three decades ago, it took an act of Congress to include people of color and women in federally funded clinical trials. A 2001 congressional survey of FDA-approved drugs found that eight of 10 that were taken off the market between 1997 and 2000 posed greater health risks to women than to men.
Men have been dying from Covid-19 at a higher rate than women since the early days of the pandemic. Klein, who studies immunological differences between the sexes, and her team are trying to identify a group of cells, or protein, in women that protects them from serious diseases. Simultaneous understanding of female protection and male pathology could lead to gender-specific interventions for both men and women.
It is widely recognized that sex is the next frontier in personalized medicine, and including it at all stages will improve scientific rigor. There are many signs of a paradigm shift, with researchers now studying, observing and measuring the influence of gender on research outcomes.
Toward this worldview, an international set of guidelines was established in 2016 for editors of scientific and medical journals to explicitly report effects by sex and gender; a growing list of peer-reviewed journals have adopted them. The world leader in biomedical funding, the NIH, is doubling down on the study of sex and sex differences as fundamental variables in research by stepping up training and creating hubs of innovation. In March, the UK’s national science and research funding body announced that later this year it “will require gender to be specified in the experimental design of grant applications involving animals and tissues. and human and animal cells”.
When I volunteered to participate in Moderna’s Phase 3 vaccine trial, the process wasn’t complicated, although it did take a leap of faith. Apart from the incident of fever, I am ready to participate in future clinical trials. But before I sign up for the next one, I’ll ask if preclinical research included sex as a biological variable. And if not, I will consider volunteering elsewhere.
Dawn Sinclair Shapiro, a journalist and filmmaker whose credits include “The Edge of Joy” (2011) and “The State of Eugenics” (2017), is currently a master’s candidate in science writing at Johns Hopkins University.