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

Terry Nolan, Murdoch Children’s Research Institute
Sumita Roy-Ghanta, GlaxoSmithKline Vaccines
May Montellano, Department of Pediatrics, Mary Chiles General Hospital
Lily Weckx, Pediatric Infectious Diseases, Department of Pediatrics, Universidade Federal de São Paulo
Rolando Ulloa-Gutierrez, Instituto Costarricense de Investigaciones Clínicas
Eduardo Lazcano-Ponce, National Institute of Public Health of Mexico
Angkool Kerdpanich, Infectious Diseases Unit, Department of Pediatrics, Phramongkutklao Hospital
Marco Aurélio Palazzi Safadi, Department of Pediatrics, Faculdade de Ciências Médicas da Santa Casa de São Paulo
Aurelio Cruz-Valdez, National Institute of Public Health of Mexico
Sandra Litao, Department of Pediatrics, De La Salle Health Sciences Institute
Fong Seng Lim, National Healthcare Group Polyclinics
Abiel Mascareñas de Los Santos, Servicios Medicos Universidad Autonoma de Nuevo Leon
Miguel Angel Rodriguez Weber, Instituto Nacional de Pediatría de Mexico
Juan-Carlos Tinoco, Hospital General de Durango
Marcela Hernandez-de Mezerville, Instituto Costarricense de Investigaciones Clínicas
Idis Faingezicht, Instituto Costarricense de Investigaciones Clínicas
Pensri Kosuwon, Department of Pediatrics, Faculty of Medicine
Pio Lopez, Centro de Estudios en Infectologia Pediatrica
Charissa Borja-Tabora, Department of Health, Research Institute for Tropical Medicine
Ping Li, GlaxoSmithKline Vaccines
Serge Durviaux, GlaxoSmithKline Vaccines
Louis Fries, Novavax
Gary Dubin, GlaxoSmithKline Vaccines
Thomas Breuer, GlaxoSmithKline Vaccines
Bruce L. Innis, GlaxoSmithKline Vaccines
David W. Vaughn, GlaxoSmithKline Vaccines


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