Sex and Age Influence Flu Vaccine Response

NIAID Now | July 12, 2019

Women tend to have greater immune responses to influenza (flu) vaccines than men, and younger people tend to have stronger immune responses to vaccines than the elderly. Previous studies have linked levels of the sex steroid hormones estrogen and testosterone to altered immune function that occurs with age. 

To better understand age, sex, and gender-related differences in influenza vaccine response, NIAID-supported researchers studied samples from 50 adults of reproductive age (18 to 45 years old) and 95 older adults (65 years old and older) who had received the vaccine for the flu strain known as H1N1 and evaluated their immune responses. The immune response to the vaccine, including levels of the immune protein interleukin-6 and virus-fighting proteins called antibodies, was much stronger in younger women than in older women, and it was stronger in women of all ages than in men of comparable age. The enhanced development of virus-neutralizing antibodies in women correlated with higher levels of estrogen. By contrast, higher levels of testosterone in men were associated with reduced development of neutralizing antibodies.

To test how differences in age and sex influence vaccine-induced protection against disease, researchers vaccinated male and female mice against influenza and then compared their immune responses to influenza infection. Similar to humans, the greatest immune response to influenza vaccination occurred in younger female mice, and these younger females were better protected against influenza following vaccination compared with male mice of similar ages. Levels of estrogen positively correlated with improved levels of neutralizing antibodies, and furthermore, experimental manipulation of levels of estrogen in mice directly influenced the antibody response to vaccination.

Together, these findings suggest an enhancing effect of estrogen and an inhibitory effect of testosterone on the development of neutralizing antibody immune responses to vaccination in humans. It may therefore be advantageous for vaccine formulations and dosages to be tailored on the basis of both sex and age in order to optimize the immune response and the ability of vaccine to protect against infection. 

Reference: Potluri T et al. Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females. NPJ Vaccines. 2019 July 12; 4:29.

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