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Antibody Response and Protection After Receipt of Inactivated Influenza Vaccine: A Systematic Review

We summarize evidence from RCTs and observational studies in which researchers compare immunogenicity and VE after 1 or 2 IIV doses in children. CONTEXT: Children are at increased risk of influenza-related complications. Public health agencies recommend 2 doses of influenza vaccine for children 6 months through 8 years of age receiving the vaccine for the first time. OBJECTIVE: To systematically review studies comparing vaccine effectiveness (VE) and immunogenicity after 1 or 2 doses of inactivated influenza vaccine (IIV) in children. DATA SOURCES: Data sources included Medline, Embase, and Cochrane Library databases. STUDY SELECTION: We included studies published in a peer reviewed journal up to April 2, 2019, with available abstracts, written in English, and with children aged 6 months through 8 years. DATA EXTRACTION: VE among fully and partially vaccinated children was compared with that of unvaccinated children. We extracted geometric mean titers of serum hemagglutination inhibition (HAI) antibodies against influenza A(H1N1), A(H3N2), and B-lineage vaccine antigens after 1 and 2 IIV doses. Outcomes were evaluated by age, timing of doses, vaccine composition, and prevaccination titers. RESULTS: A total of 10 VE and 16 immunogenicity studies were included. VE was higher for fully vaccinated groups than partially vaccinated groups, especially for children aged 6–23 months. Our findings show increased HAI titers after 2 doses, compared with 1. Older children and groups with prevaccination antibodies have robust HAI titers after 1 dose. Similar vaccine strains across doses, not the timing of doses, positively affects immune response. LIMITATIONS: Few studies focused on older children. Researchers typically administered one-half the standard dose of IIV. HAI antibodies are an imperfect correlate of protection. CONCLUSIONS: Findings support policies recommending 2 IIV doses in children to provide optimal protection against influenza.