Is there a difference in the immune response, efficacy, effectiveness and safety of seasonal influenza vaccine in males and females? - A systematic review.

Introduction: Seasonal influenza is an important cause of morbidity and mortality, despite being vaccine-preventable. Sex factors (genes and hormones) seem to impact individuals' susceptibility to infectious diseases and their response to vaccination. However, most vaccine studies do not explicitly assess sex differences in vaccine response, but rather adjust for sex.

Methods: We conducted a systematic review to analyze immunogenicity, efficacy, effectiveness and/or safety of seasonal influenza vaccine data stratified by sex. We searched PubMed, EMBASE, CINAHL, Web of Science and clinicaltrials.gov for observational studies and phase III/IV trials from January 1990 to June 2018, published in English or French. Two reviewers independently screened all references, then proceeded to data extraction and quality assessment using the Cochrane tools (RoB and ROBINS-I) on included studies.

Results: Of the 5,745 citations retrieved, 46 studies were included in the SR. Overall, 18 studies assessed immunogenicity, 1 estimated efficacy, 6 measured effectiveness and 25 evaluated safety of seasonal influenza vaccine in females and males (four studies reported on two sex-stratified outcomes concomitantly).

Conclusion: No clear conclusion could be drawn regarding the effect of sex on the immunogenicity and effectiveness of seasonal influenza vaccine, but higher rates of adverse events following immunization (AEFIs) were reported in females. The heterogeneity of data and studies' low quality prevented us from conducting a meta-analysis. There is a need to emphasize on the appropriate use of the terms sex and gender in biomedical research. Evidence of higher quality is needed to better understand sex differences in response to influenza vaccine.