The purpose of this study is to consolidate the cross-protection offered by influenza vaccines against circulating influenza A or B viruses that are not antigenically well-matched to vaccine strains and to determine the degree of cross-protection separately for influenza A and influenza B, through a systematic review of the literature.

The research question of this project is: "what is the cross-protection afforded by vaccination (using an LAIV, TIV, or other type of vaccine) against influenza A or B and their subtypes and lineages?" The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Statement will be used to guide the reporting of this review. Studies reporting cross-protection data after vaccination with approved formulations of influenza vaccines with influenza A or B will be included. Inclusion will not be limited by publication status, or year of dissemination but will be limited to randomized clinical trials (RCTs) and quasi-RCTs comparing influenza vaccine(s) with placebo. Only RCTs written in English will be included. A meta-analysis will be conducted if there is sufficient data.

Inclusion Criteria:

• Healthy children, adults or the elderly will be included that participated in randomized clinical trials (RCTs) and quasi-RCTs comparing influenza vaccine(s) with placebo.
• Placebo-controlled randomized clinical trials (RCTs) reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of influenza strains that differed from those circulating.
• All influenza vaccines will be included, and will be categorized as TIV, LAIV, and others (that is, non-TIV or non-LAIV).
• Only RCTs written in English will be included.

Exclusion Criteria:

• RCTs which are not providing any data will be excluded.
• Studies using rapid influenza diagnostic tests will not be included, as their sensitivity is low (especially during flu season) and false positives are common during low activity seasons.
• Laboratory-confirmed influenza through antibody assay as part of the primary outcome will not be included, as this is a less sensitive test than PCR and viral culture.

Healthy subjects vaccinated with an influenza vaccine.