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Influenza virus infection is a major cause of morbidity and mortality in at risk populations. Children, especially under the age of two, are at an increased risk of complications associated with influenza virus infection. Evidence suggests that a single dose of influenza vaccine does not adequately protect children against circulating influenza virus. The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunizations Practices (ACIP) recommends two doses of influenza vaccine, spaced at least four weeks apart, before the beginning of the influenza season for children between the ages of 6 months through 8 years receiving influenza vaccine for the first time. The initial dose is thought to prime the immune system, and the second dose is thought to mount a protective antibody response. We conducted a systematic literature review to summarize current evidence from randomized controlled trials (RCTs) and observational studies that compared immunogenicity and vaccine effectiveness (VE) after one or two doses of influenza vaccine in children to evaluate the evidence basis for the CDC recommendations. The search identified 727 unique articles and 82 were screened in full text for eligibility. A total of 26 studies met inclusion criteria, 16 immunogenicity and 10 VE studies. Overall, the evidence demonstrates increased immunogenicity and VE after two doses of influenza

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