title: Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial.
abstract: BACKGROUND
  Inactivated quadrivalent influenza vaccine (IIV4) containing two influenza A strains and one strain from each B lineage (Yamagata and Victoria) may offer broader protection against seasonal influenza than inactivated trivalent influenza vaccine (IIV3), containing a single B strain. This study examined the safety, immunogenicity, and lot consistency of an IIV4 candidate.
  
  
  METHODS
  This phase III, randomized, controlled, multicenter trial in children/adolescents (9 through 17 years) and adults (18 through 60 years) was conducted in Australia and in the Philippines in 2012. The study was double-blind for IIV4 lots and open-label for IIV4 vs IIV3. Children/adolescents were randomized 2:2:2:1 and adults 10:10:10:1 to receive one of three lots of IIV4 or licensed IIV3. Safety data were collected for up to 6 months post-vaccination. Hemagglutination inhibition and seroneutralization antibody titers were assessed pre-vaccination and 21 days post-vaccination.
  
  
  RESULTS
  1648 adults and 329 children/adolescents received IIV4, and 56 adults and 55 children/adolescents received IIV3. Solicited reactions, unsolicited adverse events, and serious adverse events were similar for IIV3 and IIV4 recipients in both age groups. Injection-site pain, headache, malaise, and myalgia were the most frequently reported solicited reactions, most of which were mild and resolved within 3 days. No vaccine-related serious adverse events or deaths were reported. Post-vaccination antibody responses, seroconversion rates, and seroprotection rates for the 3 strains common to both vaccines were comparable for IIV3 and IIV4 in both age groups. Antibody responses to IIV4 were equivalent among vaccine lots and comparable between age groups for each of the 4 strains. IIV4 met all European Medicines Agency immunogenicity criteria for adults for all 4 strains.
  
  
  CONCLUSIONS
  In both age groups, IIV4 was well tolerated and caused no safety concerns, induced robust antibody responses to all 4 influenza strains, and met all EMA immunogenicity criteria for adults.
  
  
  BACKGROUND
  NCT01481454.
authors.affiliation: University of the East Ramon Magsaysay Memorial Medical Center, 64 Aurora Boulevard, Barangay Doña Imelda, Quezon City, Philippines. Electronic address: jccarlosmd@yahoo.com.
authors.forename: Josefina B
authors.initials: JB
authors.lastname: Cadorna-Carlos
authors.affiliation: Melbourne School of Population and Global Health, University of Melbourne, 207 Bouverie Street, Melbourne, Victoria 3010, Australia. Electronic address: t.nolan@unimelb.edu.au.
authors.forename: Terry
authors.initials: T
authors.lastname: Nolan
authors.affiliation: Research Institute for Tropical Medicine, Corporate Ave, Muntinlupa City, Metro Manila, Philippines. Electronic address: cbtabora@yahoo.com.
authors.forename: Charissa Fay
authors.initials: CF
authors.lastname: Borja-Tabora
authors.affiliation: Philippine Children's Medical Center, Agham Road, Quezon City, Metro Manila, Philippines. Electronic address: jimson2@me.com.
authors.forename: Jaime
authors.initials: J
authors.lastname: Santos
authors.affiliation: Our Lady of Remedies Clinic, Manila, Philippines. Electronic address: csmontalban@yahoo.com.
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Montalban
authors.affiliation: AusTrials, 14 Primrose Street, Sherwood, Queensland 4075, Australia; School of Medicine, University of Queensland, Queensland 4072, Australia. Electronic address: freddelooze@austrials.com.au.
authors.forename: Ferdinandus J
authors.initials: FJ
authors.lastname: de Looze
authors.affiliation: Doctors of Ivanhoe, 131 Upper Heidelberg Rd, Ivanhoe, Victoria 3079, Australia. Electronic address: peter@dr131.com.au.
authors.forename: Peter
authors.initials: P
authors.lastname: Eizenberg
authors.affiliation: Emeritus Research, 291 Wattletree Rd, Malvern East, Victoria 3145, Australia. Electronic address: stephenhall@emeritusresearch.com.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hall
authors.affiliation: Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy-l'Étoile, France. Electronic address: Martin.Dupuy@sanofipasteur.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Dupuy
authors.affiliation: Sanofi Pasteur, 6 Raffles Quay, 048580, Singapore. Electronic address: buddy.bello@gmail.com.
authors.forename: Yanee
authors.initials: Y
authors.lastname: Hutagalung
authors.affiliation: Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy-l'Étoile, France. Electronic address: Stephanie.Pepin@sanofipasteur.com.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Pépin
authors.affiliation: Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy-l'Étoile, France. Electronic address: Melanie.Saville@sanofipasteur.com.
authors.forename: Melanie
authors.initials: M
authors.lastname: Saville
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001315:Australia; D002648:Child; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D010679:Philippines; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: Immunogenicity; Influenza; Quadrivalent; Safety; Trivalent; Vaccine