A Systematic Review of Studies of the Effect of Influenza Vaccine Against Mismatched Strains
A Systematic Review of Studies of the Effect of Influenza Vaccine Against Mismatched Strains
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.