Sex Can Make All The Difference
by Rachel Butch
What if I were to say that your annual flu shot might not be as effective as you think?
A 2010 study indicates that sex hormones may play a major role in the efficacy of common vaccines. “The Xs and Y of Immune Responses to Viral Vaccines,” published in The Lancet Infectious Diseases, showed that many factors associated with sex can affect how our immune systems respond to immunization. As it turns out, women tend to have a stronger response than men. While the underlying cause of this difference is poorly understood, early research suggests that sex hormones play a crucial role in the observed variation. Ultimately, researchers hope that the results from this study will shed light on how we might create more effective vaccination programs in the future.
Male and female sex hormones, androgens and estrogens respectively, are closely associated with immune responses. In fact, promoters of several innate immunity genes contain sites that recognize these hormones. As our innate immune system is our body’s first line of defense against infectious pathogens, this interaction allows hormones to directly influence the way our immune system responds to the antigens present in vaccines.
The data in the study suggest that the increased presence of female sex hormones stimulates activity in the innate immune system, making women more responsive to immunization with a heightened immune response for 10 weeks after vaccination. However, this robust response can become a double-edged sword for vaccines, such as the yellow fever vaccine, that incite an inflammatory outcome. The enhanced response in women may underlie a greater incidence of side effects associated with inflammation, in comparison to men. These unwanted manifestations could vary between different vaccines, but typically include swelling at the injection site, as well as joint and limb pain. Specifically for the Measles, Mumps and Rubella (MMR) vaccine, severe side effects such as fever and gland inflammation have been seen in significantly more females than males.
Another research study in 2013 gave further insight into how male hormones affect vaccination efficacy. In a paper titled “Systems Analysis of Sex Differences Reveals an Immunosuppressive Role for Testosterone in the Response to Influenza Vaccination,” a collaboration of researchers from Stanford University, the University of Bordeaux and the University of North Carolina at Chapel Hill explained how women not only have an increased response to the influenza vaccine, but men with the highest testosterone levels have the lowest antibody response to the vaccine of any population. These findings hold that, while estrogens increase activity, androgens actually suppress the activity of immune cells.
It is well known that women’s immune systems are heavily altered during pregnancy. Specifically, 17ß-oestradiol (a type of estrogen hormone) and progesterone are found in elevated concentrations during pregnancy. High concentrations of progesterone are correlated to increased helper T cell populations—immune cells sensitive to antibodies in your body. While these cells seem to elevate the immune tolerance of the fetus during pregnancy, they might also affect a woman’s response to vaccination. The hormonal differences between pregnant and non-pregnant females are so profound that the authors of the 2010 study suggest studying vaccinations in terms of three groups: males, pregnant females and non-pregnant females.
These scientific findings beg the question: Do women really need to have the same vaccine dose as men if their response is so amplified? Conversely, do men perhaps need higher doses? Vaccine trials that address these questions are extremely uncommon as vaccine efficacy studies aim to establish a dose that generates the strongest immune responses in the largest number of people, studying mainly antiviral antibody titers or total T-cell responses at late time points after vaccination, which do not capture the kinetics of sex-specific immune responses within the critical 10 day period. Essentially, instead of fine-tuning vaccine doses to these substantially different populations, we are vaccinating the average.
So how can we change the way that these kinds of studies are performed? Here again, the authors of the 2010 study recommend taking more frequent biological samples from vaccinated subjects in order to establish a database of information for further study. They suspect that hormone changes related to age, contraception use and pregnancy all affect vaccination efficacy. Through her research, Sabra Klein, PhD, co-author of the 2010 study, strives to make more people aware of this issue. “There are complex interactions with our biology on either how we behave or what we do and how this may influence the course, as well as the outcome of infectious diseases. I want to plant the seed of thinking about how our biological differences can also affect how we handle an infectious disease.”
With further study, modern science hopes to revolutionize how we look at vaccines across the general population by optimizing dose administrations to fit each patient’s individual biology. For now, we can only wait and see what the next several years hold for this novel field of study.