Relative Efficacy of AS03-Adjuvanted Pandemic Influenza A(H1N1) Vaccine in Children: Results of a Controlled, Randomized Efficacy Trial

Background. the vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010-2011.Methods. A total of 6145 children were randomly assigned at a ratio of 1: 1: 1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009 (H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed.Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. the VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%-93.4%). the benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group.Conclusion. the 4-8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics.GlaxoSmithKline BiologicalsUniv Melbourne, Murdoch Childrens Res Inst, Carlton, Vic 3010, AustraliaUniv Melbourne, Melbourne Sch Populat & Global Hlth, Carlton, Vic 3010, AustraliaGlaxoSmithKline Vaccines, King of Prussia, PA USANovavax, Rockville, MD USAMary Chiles Gen Hosp, Dept Pediat, Manila, PhilippinesDe La Salle Hlth Sci Inst, Dept Pediat, Dasmarinas City, PhilippinesRes Inst Trop Med, Dept Hlth, Muntinlupa, PhilippinesUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilFac Ciencias Med Santa Casa São Paulo, Dept Pediat, São Paulo, BrazilAssoc Fundo Incent Pesquisa, São Paulo, BrazilInst Costarricense Invest Clin, San Jose, Costa RicaNatl Inst Publ Hlth Mexico, Cuernavaca, Morelos, MexicoUniv Autonoma Nuevo Leon, Serv Med, Monterrey, MexicoInst Nacl Pediat Mexico, Mexico City, DF, MexicoHosp Gen Durango, Durango, MexicoPhramongkutklao Hosp, Infect Dis Unit, Dept Pediat, Bangkok, ThailandKhon Kaen Univ, Dept Pediat, Fac Med, Khon Kaen, ThailandNatl Healthcare Grp Polyclin, Singapore, SingaporeCtr Estudios Infect Pediat, Cali, ColombiaGlaxoSmithKline Vaccines, Wavre, BelgiumGlaxoSmithKline Vaccines, Rixensart, BelgiumUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilWeb of Scienc

Respiratory viruses and influenza-like illness: Epidemiology and outcomes in children aged 6 months to 10 years in a multi-country population sample

Background: Better population data on respiratory viruses in children in tropical and southern hemisphere countries is needed. Methods: The epidemiology of respiratory viruses among healthy children (6 months to < 10 years) with influenza-like illness (ILI) was determined in a population sample derived from an influenza vaccine trial (NCT01051661) in 17 centers in eight countries (Australia, South East Asia and Latin America). Active surveillance for ILI was conducted for approximately 1 year (between February 2010 and August 2011), with PCR analysis of nasal and throat swabs. Results: 6266 children were included, of whom 2421 experienced 3717 ILI episodes. Rhinovirus/enterovirus had the highest prevalence (41.5%), followed by influenza (15.8%), adenovirus (9.8%), parainfluenza and respiratory syncytial virus (RSV) (both 9.7%), coronavirus (5.6%), human metapneumovirus (5.5%) and human bocavirus (HBov) (2.0%). Corresponding incidence per 100 person-years was 29.78, 11.34, 7.03, 6.96, 6.94, 4.00, 3.98 and 1.41. Except for influenza, respiratory virus prevalence declined with age. The incidence of medicallyattended ILI associated with viral infection ranged from 1.03 (HBov) to 23.69 (rhinovirus/ enterovirus). The percentage of children missing school or daycare ranged from 21.4% (HBov) to 52.1% (influenza). Conclusions: Active surveillance of healthy children provided evidence of respiratory illness burden associated with several viruses, with a substantial burden in older children. (C) 2016 Published by Elsevier Ltd on behalf of The British Infection Association.GlaxoSmithKline Biologicals S.AGSK Vaccines, 20 Ave Fleming, B-1330 Wavre, BelgiumCtr Estudios Infectol Pediat, Cali, ColombiaUniv Fed Sao Paulo, Dept Pediat, Pediat Infect Dis, Sao Paulo, BrazilRes Inst Trop Med, Dept Hlth, Muntinlupa, PhilippinesInst Costarricense Invest Clin, San Jose, Costa RicaNatl Inst Publ Hlth Mexico, Cuernavaca, Morelos, MexicoPhramongkutklao Hosp, Dept Pediat, Infect Dis Unit, Bangkok, ThailandInst Nacl Pediat Mexico, Mexico City, DF, MexicoUniv Autonoma Nuevo Leon, Med Serv, Monterrey, MexicoHosp Gen Durango, Durango, MexicoFac Ciencias Med Santa Casa Sao Paulo, Sao Paulo, BrazilAssoc Fundo Incent Pesquisa, Dept Pediat, Sao Paulo, BrazilNatl Univ Singapore, Natl Healthcare Grp Polyclin, Singapore, SingaporeGSK Vaccines, King Of Prussia, PA USAUniv Melbourne, Murdoch Childrens Res Inst, Carlton, Vic, AustraliaUniv Melbourne, Melbourne Sch Populat & Global Hlth, Carlton, Vic, AustraliaPediatric Infectious Diseases, Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

Relative efficacy of AS03-adjuvanted pandemic influenza A(H1N1) vaccine in children: Results of a controlled, randomized efficacy trial

Background. The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to /California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed. Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%-93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group. Conclusion. The 4-8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661. © 2014 The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America