title: Immunogenicity and safety of inactivated quadrivalent influenza vaccine in adults: A systematic review and meta-analysis of randomised controlled trials.
abstract: A quadrivalent influenza vaccine (QIV) includes two A strains (A/H1N1, A/H3N2) and two B lineages (B/Victoria, B/Yamagata). The presence of both B lineages eliminate potential B lineage mismatch of trivalent influenza vaccine (TIV) with the circulating strain.
  
  
  
  Electronic database searches of Medline, Embase, Cochrane Central Register of Controlled Trials (CCRCT), Scopus and Web of Science were conducted for articles published until June 30, 2015 inclusive. Articles were limited to randomised controlled trials (RCTs) in adults using inactivated intramuscular vaccine and published in English language only. Summary estimates of immunogenicity (by seroprotection and seroconversion rates) and adverse events outcomes were compared between QIV and TIV, using a risk ratio (RR). Studies were pooled using inverse variance weights with a random effect model and the I(2) statistic was used to estimate heterogeneity.
  
  
  
  A total of five RCTs were included in the meta-analysis. For immunogenicity outcomes, QIV had similar efficacy for the three common strains; A/H1N1, A/H3N2 and the B lineage included in the TIV. QIV also showed superior efficacy for the B lineage not included in the TIV; pooled seroprotection RR of 1.14 (95%CI: 1.03-1.25, p=0.008) and seroconversion RR of 1.78 (95%CI: 1.24-2.55, p=0.002) for B/Victoria, and pooled seroprotection RR of 1.12 (95%CI: 1.02-1.22, p=0.01) and seroconversion RR of 2.11 (95%CI: 1.51-2.95, p<0.001) for B/Yamagata, respectively. No significant differences were found between QIV and TIV for aggregated local and systemic adverse events within 7days post-vaccination. There were no vaccine-related serious adverse events reported for either QIV or TIV. Compared to TIV, injection-site pain was more common for QIV, with a pooled RR of 1.18 (95%CI: 1.03-1.35, p=0.02).
  
  
  
  In adults, inactivated QIV was as immunogenic as seasonal TIV, with equivalent efficacy against the shared three strains included in TIV, and a superior immunogenicity against the non-TIV B lineage.
authors.affiliation: School of Public Health and Community Medicine, University of New South Wales, NSW, Sydney, Australia. Electronic address: a.moa@unsw.edu.au.
authors.forename: Aye M
authors.initials: AM
authors.lastname: Moa
authors.affiliation: School of Public Health and Community Medicine, University of New South Wales, NSW, Sydney, Australia.
authors.forename: Abrar A
authors.initials: AA
authors.lastname: Chughtai
authors.affiliation: School of Public Health and Community Medicine, University of New South Wales, NSW, Sydney, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Muscatello
authors.affiliation: School of Public Health and Community Medicine, University of New South Wales, NSW, Sydney, Australia.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Turner
authors.affiliation: School of Public Health and Community Medicine, University of New South Wales, NSW, Sydney, Australia; College of Public Service & Community Solutions, Arizona State University, Phoenix, AZ, United States.
authors.forename: C Raina
authors.initials: CR
authors.lastname: MacIntyre
mesh_terms: D000328:Adult; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D000071497:Immunogenicity, Vaccine; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D000069078:Seroconversion; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000276:immunology*
chemical_list: D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: Immunogenicity; Influenza vaccine; Intramuscular; QIV; Quadrivalent