Vaccine Immunity in Women Decreases After Menopause, Researchers Say

Declining levels of estrogen in postmenopausal women diminish their immune response to a flu vaccination, a study published in July by the journal NPJ Vaccines says

Researchers at the Johns Hopkins Bloomberg School of Public Health sought to discover the effects that differing sexes and age have on immune responsiveness. Aging has been shown to cause a progressive decline and remodeling of the immune system in older individuals, but whether this occurs similarly in men and women as they age has not been studied.

Of the few studies conducted on sex-related differences in vaccine antibody responsiveness, it has been shown that “aged females reportedly have greater hemagglutinin inhibition (HAI) antibody responses to both seasonal and pandemic influenza vaccines than males, whereas aged males appear to have greater antibody responses to the pneumococcal and tetanus, diphtheria, and pertussis vaccines than females,” said the authors. The heightened HAI antibody titers in adult women between the ages of 18-49 have been shown to be twice than that of adult males in the same age group. While age has been studied extensively, and sex differentiation intermittently, age-related sex differences on immune responsiveness has remained overlooked.

The Johns Hopkins study evaluated serum samples of a monovalent 2009 H1N1 vaccine for influenza vaccine-induced sex/gender differences in 50 people who were of reproductive age (18-45) and 95 who were non-reproductive age (65 years or older). Only IFN, IL-6, I1-8, IL-10, and TNF were detected in the serum, with higher concentrations of IL-6 post-vaccination found in reproductive-age females as opposed to postmenopausal adult females and all men. As IL-6 is crucial for germinal center formation, antibody production, and class switching, heightened concentrations immediately after vaccination can suggest that women still in their reproductive years should have stronger immune response than postmenopausal women. Concentration levels of the sex steroid hormone estradiol, a form of estrogen, was found to be significantly lower in postmenopausal than reproductive-age women. The correlation between estradiol and a higher neutralizing antibody seroconversion provides further evidence of the diminished vaccine immunity to flu vaccines for older women.

Lead study author Sabra Klein, PhD, from Johns Hopkins Bloomberg School of Public Health and an associate professor in the Department of Molecular Microbiology and Immunology, highlighted the importance of “tailoring vaccine formulations and dosages based on the sex of the vaccine recipient as well as their age.” The stark difference in anti-flu antibody responsiveness between younger and older women in the study points to the immediate need to customize vaccine dosages, she said.

Similar experiments on mice revealed comparable results to that of humans. Researchers found the evidence of the association between vaccine responsiveness and sex hormone levels as “causal.” Young female mice had higher bloodstream levels of estradiol compared to older, postmenopausal female mice similar to that found in humans. Researchers removed the ovaries of female mice to cut down estradiol production and accentuate its importance among tested subjects. The implementation of artificially resupplied estradiol in these low-hormone female mice then accounted toward a stronger vaccine antibody responsiveness.

“What we show here is that the decline in estrogen that occurs with menopause impacts women’s immunity,” said Klein. Age has always been correlated to a lower vaccine responsiveness, but the significant difference between younger and older women showcases a vital alteration for vaccine dosage. Postmenopausal women need a tailored vaccine dose to combat their heightened susceptibility to infectious diseases once their estrogen levels decline.

Reference

Klein SL, Potluri T, Fink AL, et al. Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females. [published online July 12, 2019]. NPJ Vaccines. doi: 10.1038/s41541-019-0124-6