Flu Vaccine More Effective in Women, Study Finds


New research finds that the flu vaccine is more successful in women than in men, but the complexity of the issue makes it difficult to know exactly why that is.

Danuta Skowronski, MD, FRCPC

Sex appears to have a significant impact on the efficacy of the influenza vaccine, according to a new study. However, the authors conclude that more evidence is needed before scientists can determine whether influenza prevention strategies should vary by sex.

Investigators have long identified a number of ways sex can correlate with health when it comes to influenza. For instance, women tend to have greater exposure to influenza due to historic gender norms under which women serve as primary caregivers at higher rates than men. However, men have tended to have higher rates of mortality and morbidity when diagnosed with the flu. Women are also more likely to be vaccinated than men, and they tend to seek health care more quickly when they are sick.

Still, investigators wanted to find out the extent to which sex itself—not simply cultural norms around sex—might affect vaccine effectiveness. To study the question, the investigators looked at a database of Canadian patients over 7 flu seasons, from 2010-2011 to 2016-2017. Patients were included if they were at least 1-year-old and saw a doctor within 7 days of the onset of flu-like symptoms. Vaccination status was documented based on patient self-reports.

Only patients who had been vaccinated at least 2 weeks prior to the diagnosis of influenza were included in the study.

The data showed that women were slightly less likely than men (40% versus 43%) to have a positive flu test, and they were also more likely (29% versus 23%) to have been vaccinated against the flu.

However, overall vaccine effectiveness for women was considerably higher, at 49%, versus just 38% for men. The difference varied somewhat by strain, with the greatest gaps seen in the A (H3N2) and B (Victoria) strains. Meanwhile, among unvaccinated patients, there was no such sex-based difference in influenza rates.

“Together, these findings suggest that biological sex differences in the response to vaccine, rather than gender differences in health care seeking or vaccination status reporting, likely explains the observed differences in influenza VE between males and females,” wrote the authors.

The authors noted that previous research has suggested women have “stronger innate and adaptive immune responses, including more pronounced antibody response to influenza vaccine, in association with higher rates of local and systemic adverse events following immunization.”

Another potential biological cause for the disparity is that testosterone can be immunosuppressive at high levels, the authors said.

The sex-based vaccine effectiveness gap was most pronounced among older adults. A significant gender gap was also shown among prepubescent children.

Still, the investigators say that further study would be needed to confirm the role of sex, and to determine whether a sex-specific influenza prevention strategy is warranted.

“Others have previously suggested that influenza vaccine design should take into account the biological differences in males and females and may need to be tailored to an individual’s sex,” corresponding author Danuta Skowronski MD, FRCPC, of the British Columbia Centre for Disease Control, told Contagion ®. “Our study does not resolve that but underscores the need for further evaluation and more definitive investigation of these possible interactions.”

If the findings are confirmed, the investigators say one day physicians and vaccine developers might start taking sex into account when developing influenza prevention plans.

The study is titled, “Should sex be considered as an effect modifier in the evaluation of influenza vaccine effectiveness?” The open-access article was published this week in Open Forum Infectious Diseases.

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