For years, Sabra Klein has been trying to start a
conversation about sex. The Johns
Hopkins immunologist studies why women have stronger immune systems than men—a
phenomenon that underlies the fact that women are three times more
likely to develop autoimmune diseases—but are also better protected by vaccines.
The latter, however, has gotten very little attention from vaccine makers or
doctors.
A flu vaccine paper published today argues that it really should. Testosterone
suppresses the immune system, and that, of course, disproportionately concerns
men. The study in PNAS from Mark
Davis’s lab at Stanford also identifies a cluster of genes affected by
testosterone and somehow involved in immunity. Davis wasn’t looking for sex
differences in his initial flu vaccine study, but that’s what he found. And
that’s when he got in touch with Klein.
Davis’s study appears in a major journal, with a press
office that chose to send his paper out to journalists in advance. This may
just kick up enough fuss about sex differences in vaccine response to get
pharmaceutical companies to pay attention. Klein calls the new study, “amazingly
exciting.” “I hope this does continue to
generate greater discussions,” she says.
Why does it matter?
Clinical trials usually treat sex as a
confounding variable to be factored out, rather than a variable to be studied.
Vaccines that protect women but not men may not look effective when the two
sexes are lumped together, prematurely ending a promising vaccine for the half
the population. That’s on top of another problem: women are often underrepresented
in clinical trials in the first place.
Another issue is dosing: Men may need larger doses. The flip side is also that
vaccines have side effects—a virus, weakened or dead, is still being
injected into your body, after all—and a stronger immune system in women can mean stronger side
effects like fever, headache, and fatigue. The flu vaccine is a voluntary, and
one crummy experience can keep women from coming back. By the way, PSA: If you haven’t yet, you
should go get your flu
shot.
What does testosterone have to do with it?
At Stanford, Davis started out looking for reasons the flu
vaccine worked better in some people than others, as measured by the antibody response. A vaccine teaches your body to create antibodies, or molecules that identify and neutralize a specific pathogen. A big factor in antibody response, he found, was
sex.
But then he dug deeper, analyzing the testosterone levels to find that
even within men, those with high testosterone levels had a lower antibody
response to the flu vaccine. His lab also identified a new set of genes
involved in the synthesis of fats that are also correlated with testosterone
levels and antibody response to vaccines. The exact functions of those genes are fodder for future research.
“I think absolutely that
vaccine makers need to give a think about these are very real male-female
differences,” said Davis. “This
hasn’t really been on the front burner, but now I think it should.”
What now?
When I first spoke to Klein months ago, she said her
research had been gaining more mainstream attention. She was being invited to more talks.
The HPV vaccine, which primarily protects against cervical cancer, had paved
the way for thinking about gender with respect to vaccines. (Though the vaccine is now
approved for both young men and women.) She hopes the FDA will incorporate sex
into clinical trials and vaccine design.
A whole host of drugs from sleeping pills to blood pressure
medications have been found to be metabolized differently in men and women in recent years. Earlier this year, the FDA reduced the recommended dose of Ambien for women by half. It’ll take more research to figure out exactly how and why the immune systems of men and women are different, but at
this point, it’s clear they are.
Photo via Syda Productions/Shutterstock
