BACKGROUND: It has not yet been demonstrated whether 2 doses of inactivated quadrivalent influenza vaccine (IIV4) prime a booster response in infants. We evaluated the anamnestic immune response to an IIV4 in children 17-48 months of age. METHODS: Children were randomized to 2 doses of IIV4 or control in the primary phase III study (NCT01439360). One year later, in an open-label revaccination extension study (NCT01702454), a subset of children who received IIV4 in the primary study (primed group) received 1 IIV4 dose and children who received control in the primary study (unprimed) received 2 IIV4 doses 28 days apart. The primary objective was to evaluate hemagglutination inhibition (HI) antibody titers 7 days after first IIV4 vaccination in the per-protocol cohort (N = 224 primed; N = 209 unprimed). Neutralizing and antineuraminidase antibodies were also measured. Safety was analyzed in the total vaccinated cohort (N = 241 primed; N = 229 unprimed). RESULTS: An anamnestic response was observed in primed children relative to unprimed controls, measured by age-adjusted geometric mean HI titer ratios against strains homologous (A/H1N1: 9.0; B/Victoria: 3.9) and heterologous (A/H3N2: 2.7; B/Yamagata: 6.7) to those in the primary vaccination series. The anamnestic response in primed children included increases in neutralizing antibodies (mean geometric increase: 5.0-10.6) and antineuraminidase antibodies (4.9-8.8). No serious adverse events related to vaccination were reported. CONCLUSIONS: In this study, 2-dose priming with IIV4 induced immune memory that was recalled with 1-dose IIV4 the following year to boost HI, antineuraminidase and neutralizing antibodies, even though the IIV4 strain composition partially changed.

CAP Centelles Barcelona Spain

Faculty of Medicine University Hospital and Charles University Hradec Králové Czech Republic

From the GSK Wavre Belgium

Grupo de Investigación en Genética Vacunas Infecciones y Pediatría Galicia Spain

GSK Bangalore India

GSK King of Prussia Pennsylvania

GSK Rockville Maryland

Hospital de Antequera Málaga Spain

Hospital Materno Infantil La Paz Madrid Spain

Infectious Diseases Outpatient Clinic Debica Poland

Institut Pediàtric Marès Riera Girona Spain

Instituto Hispalense de Pediatría Sevilla Spain

National Institute of Health Research Wellcome Trust Clinical Research Facility University of Southampton and University Hospital Southampton NHS Foundation Trust Southampton United Kingdom

Pediatric Office Dr Renáta Růžková Prague Czech Republic

Translational Pediatrics and Infectious Diseases Department of Pediatrics Hospital Clínico Universitario de Santiago Santiago de Compostela Galicia Spain

University of Oxford and the NIHR Oxford Biomedical Research Centre Oxford United Kingdom

Vaccine Research Department FISABIO Public Health Valencia Spain

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Cromer D, van Hoek AJ, Jit M, et al. The burden of influenza in England by age and clinical risk group: a statistical analysis to inform vaccine policy. J Infect. 2014;68:363–371.. PubMed

Ruf BR, Knuf M. The burden of seasonal and pandemic influenza in infants and children. Eur J Pediatr. 2014;173:265–276.. PubMed PMC

Fowlkes A, Steffens A, Temte J, et al. ; Influenza Incidence Surveillance Project Working Group. Incidence of medically attended influenza during pandemic and post-pandemic seasons through the Influenza Incidence Surveillance Project, 2009-13. Lancet Respir Med. 2015;3:709–718.. PubMed PMC

World Health Organization. Vaccines against influenza WHO position paper – November 2012. Wkly Epidemiol Rec. 2012;87:461–476.. PubMed

Skowronski DM, Masaro C, Kwindt TL, et al. Estimating vaccine effectiveness against laboratory-confirmed influenza using a sentinel physician network: results from the 2005-2006 season of dual A and B vaccine mismatch in Canada. Vaccine. 2007;25:2842–2851.. PubMed

Skowronski DM, De Serres G, Dickinson J, et al. Component-specific effectiveness of trivalent influenza vaccine as monitored through a sentinel surveillance network in Canada, 2006-2007. J Infect Dis. 2009;199:168–179.. PubMed

Belongia EA, Kieke BA, Donahue JG, et al. ; Marshfield Influenza Study Group. Effectiveness of inactivated influenza vaccines varied substantially with antigenic match from the 2004-2005 season to the 2006-2007 season. J Infect Dis. 2009;199:159–167.. PubMed

Belshe RB, Coelingh K, Ambrose CS, et al. Efficacy of live attenuated influenza vaccine in children against influenza B viruses by lineage and antigenic similarity. Vaccine. 2010;28:2149–2156.. PubMed

Barr IG, Komadina N, Durrant C, et al. Circulation and antigenic drift in human influenza B viruses in SE Asia and Oceania since 2000. Commun Dis Intell Q Rep. 2006;30:350–357.. PubMed

Englund JA, Walter EB, Gbadebo A, et al. Immunization with trivalent inactivated influenza vaccine in partially immunized toddlers. Pediatrics. 2006;118:e579–e585.. PubMed

Levandowski RA, Regnery HL, Staton E, et al. Antibody responses to influenza B viruses in immunologically unprimed children. Pediatrics. 1991;88:1031–1036.. PubMed

Claeys C, Zaman K, Dbaibo G, et al. ; Flu4VEC Study Group. Prevention of vaccine-matched and mismatched influenza in children aged 6-35 months: a multinational randomised trial across five influenza seasons. Lancet Child Adolesc Health. 2018;2:338–349.. PubMed

Hannoun C, Megas F, Piercy J. Immunogenicity and protective efficacy of influenza vaccination. Virus Res. 2004;103:133–138.. PubMed

Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 1934;26:404–413..

Newcombe RG. Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med. 1998;17:857–872.. PubMed

Greenberg DP, Robertson CA, Landolfi VA, et al. Safety and immunogenicity of an inactivated quadrivalent influenza vaccine in children 6 months through 8 years of age. Pediatr Infect Dis J. 2014;33:630–636.. PubMed

Langley JM, Carmona Martinez A, Chatterjee A, et al. Immunogenicity and safety of an inactivated quadrivalent influenza vaccine candidate: a phase III randomized controlled trial in children. J Infect Dis. 2013;208:544–553.. PubMed PMC

Langley JM, Wang L, Aggarwal N, et al. Immunogenicity and reactogenicity of an inactivated quadrivalent influenza vaccine administered intramuscularly to children 6 to 35 months of age in 2012-2013: a randomized, double-blind, controlled, multicenter, multicountry, clinical trial. J Pediatric Infect Dis Soc. 2015;4:242–251.. PubMed PMC

Domachowske JB, Pankow-Culot H, Bautista M, et al. A randomized trial of candidate inactivated quadrivalent influenza vaccine versus trivalent influenza vaccines in children aged 3-17 years. J Infect Dis. 2013;207:1878–1887.. PubMed PMC

Wang L, Chandrasekaran V, Domachowske JB, et al. Immunogenicity and safety of an inactivated quadrivalent influenza vaccine in US children 6-35 months of age during 2013-2014: results from a phase II randomized trial. J Pediatric Infect Dis Soc. 2016;5:170–179.. PubMed PMC

Jain VK, Domachowske JB, Wang L, et al. Time to change dosing of inactivated quadrivalent influenza vaccine in young children: evidence from a phase III, randomized, controlled trial. J Pediatric Infect Dis Soc. 2017;6:9–19.. PubMed PMC

Jain VK, Rivera L, Zaman K, et al. Vaccine for prevention of mild and moderate-to-severe influenza in children. N Engl J Med. 2013;369:2481–2491.. PubMed

World Health Organization. Recommended composition of influenza virus vaccines for use in the 2012–2013 northern hemisphere influenza season. 2012. Available at: http://www.who.int/influenza/vaccines/virus/recommendations/201202_recommendation.pdf?ua=1.http://www.who.int/influenza/vaccines/virus/recommendations/201202_recommendation.pdf?ua=1. Accessed October 14, 2015.

Walter EB, Neuzil KM, Zhu Y, et al. Influenza vaccine immunogenicity in 6- to 23-month-old children: are identical antigens necessary for priming? Pediatrics. 2006;118:e570–e578.. PubMed

Couch RB, Atmar RL, Franco LM, et al. Antibody correlates and predictors of immunity to naturally occurring influenza in humans and the importance of antibody to the neuraminidase. J Infect Dis. 2013;207:974–981.. PubMed PMC

Hardelid P, Andrews NJ, Hoschler K, et al. Assessment of baseline age-specific antibody prevalence and incidence of infection to novel influenza A/H1N1 2009. Health Technol Assess. 2010;14:115–192.. PubMed

Wright PF, Thompson J, Vaughn WK, et al. Trials of influenza A/New Jersey/76 virus vaccine in normal children: an overview of age-related antigenicity and reactogenicity. J Infect Dis. 1977;136(suppl):S731–S741.. PubMed

Bernstein DI, Zahradnik JM, DeAngelis CJ, et al. Clinical reactions and serologic responses after vaccination with whole-virus or split-virus influenza vaccines in children aged 6 to 36 months. Pediatrics. 1982;69:404–408.. PubMed

Quadrivalent Influenza Vaccine Prevents Illness and Reduces Healthcare Utilization Across Diverse Geographic Regions During Five Influenza Seasons: A Randomized Clinical Trial

Zobrazit více v PubMed

ClinicalTrials.gov
NCT01702454, NCT01439360