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

Terry Nolan, Sumita Roy-Ghanta, May Montellano, Lily Weckx, Rolando Ulloa-Gutierrez, Eduardo Lazcano-Ponce, Angkool Kerdpanich, Marco Aurélio Palazzi Safadi, Aurelio Cruz-Valdez, Sandra Litao, Fong Seng Lim, Abiel Mascareñas de Los Santos, Miguel Angel Rodriguez Weber, Juan-Carlos Tinoco, Marcela Hernandez-de Mezerville, Idis Faingezicht, Pensri Kosuwon, Pio Lopez, Charissa Borja-Tabora, Ping Li, Serge Durviaux, Louis Fries, Gary Dubin, Thomas Breuer, Bruce L Innis, David W Vaughn, Terry Nolan, Sumita Roy-Ghanta, May Montellano, Lily Weckx, Rolando Ulloa-Gutierrez, Eduardo Lazcano-Ponce, Angkool Kerdpanich, Marco Aurélio Palazzi Safadi, Aurelio Cruz-Valdez, Sandra Litao, Fong Seng Lim, Abiel Mascareñas de Los Santos, Miguel Angel Rodriguez Weber, Juan-Carlos Tinoco, Marcela Hernandez-de Mezerville, Idis Faingezicht, Pensri Kosuwon, Pio Lopez, Charissa Borja-Tabora, Ping Li, Serge Durviaux, Louis Fries, Gary Dubin, Thomas Breuer, Bruce L Innis, David W Vaughn

Abstract

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. Clinical Trials Registration. NCT01051661.

Keywords: H1N1; children; efficacy; influenza virus; pandemic influenza vaccine.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Kaplan–Meier time-to-event curve for real-time polymerase chain reaction–confirmed 2009 pandemic influenza A(H1N1) infection reported from 14 days after vaccination through the end of influenza-like illness surveillance. aData are for the time-to-event analysis of the according-to-protocol cohort; bData for 1 subject were censored before the event and are thus not included. Abbreviations: Ad1, A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2; Ad2, 2 doses of A/California/7/2009(H1N1)-AS03 vaccine; NAd2, 2 doses of nonadjuvanted A/California/7/2009(H1N1) vaccine.
Figure 2.
Figure 2.
Reverse cumulative curves for hemagglutination-inhibiting (HI) antibody (Ab) titers at day 42, day 182, and day 385 in all children (ie, the according-to-protocol immunogenicity cohort). Abbreviations: Ad1, A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2; Ad2, 2 doses of A/California/7/2009(H1N1)-AS03 vaccine; HA, hemagglutinin; NAd2, 2 doses of nonadjuvanted A/California/7/2009(H1N1) vaccine.
Figure 3.
Figure 3.
Percentage of subjects reporting injection site reactions and general symptoms 0–6 days after each vaccine dose. Vertical lines indicate 95% confidence intervals. In children 100 mm in diameter, fever (ie, an oral or axillary temperature of ≥39.0°C), irritability (ie, crying that cannot be comforted or that prevents normal activity), drowsiness (ie, prevention of normal activity), and loss of appetite (not eating at all). In children 6 to 100 mm in diameter, fever (ie, an oral/axillary temperature of ≥39.0°C), and, for all other symptoms, prevention of normal activity.

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Source: PubMed

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