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Clinical Trial
. 2011 Jun 15;203(12):1729-38.
doi: 10.1093/infdis/jir172.

Dose-sparing H5N1 A/Indonesia/05/2005 pre-pandemic influenza vaccine in adults and elderly adults: a phase III, placebo-controlled, randomized study

Joanne M Langley  1 , George Risi, Michael Caldwell, Larry Gilderman, Bruce Berwald, Charles Fogarty, Terry Poling, Dennis Riff, Mira Baron, Louise Frenette, Eric Sheldon, Harry Collins, Marc Shepard, Marc Dionne, Daniel Brune, Linda Ferguson, David Vaughn, Ping Li, Louis Fries
Affiliations
Clinical Trial

Dose-sparing H5N1 A/Indonesia/05/2005 pre-pandemic influenza vaccine in adults and elderly adults: a phase III, placebo-controlled, randomized study

Joanne M Langley et al. J Infect Dis. .

Abstract

Background: Highly pathogenic avian influenza H5N1 viruses remain a threat to human health, with potential to become pandemic agents.

Methods: This phase III, placebo-controlled, observer-blinded study evaluated the immunogenicity, cross-reactivity, safety, and lot consistency of 2 doses of oil-in-water (AS03(A)) adjuvanted H5N1 A/Indonesia/05/2005 (3.75 μg hemagglutinin antigen) prepandemic candidate vaccine in 4561 adults aged 18-91 years.

Results: Humoral antibody responses in the H5N1 vaccine groups fulfilled US and European immunogenicity licensure criteria for pandemic vaccines in all age strata 21 days after the second dose. At 6 months after the administration of the primary dose, serum antibody seroconversion rates continued to fulfill licensure criteria. Neutralizing cross-clade immune responses were demonstrated against clade 1 A/Vietnam/1194/2004. Consistency was demonstrated for 3 consecutive H5N1 vaccine lots. Temporary injection-site pain was more frequent with H5N1 vaccine than placebo (89.3% and 70.7% in the 18-64 and ≥65 years strata vs 22.2% and 14.4% in the placebo groups). Unsolicited adverse event frequency, including medically attended and serious events, was similar between groups through day 364.

Conclusions: In adults and elderly adults, AS03(A)-adjuvanted H5N1 candidate vaccine was highly immunogenic for A/Indonesia/05/2005, with cross-reactivity against A/Vietnam/1194/2004. Temporary injection site reactions were more frequent with H5N1 vaccine than placebo, although the H5N1 vaccine was well tolerated overall. Clinical Trials Registration. NCT00616928.

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Figures

Figure 1.
Figure 1.
Study flow diagram.
Figure 2.
Figure 2.
Hemagglutination inhibition assay responses against the vaccine-homologous strain in the according-to-protocol immunogenicity cohort (day 42) and the day 182 immunogenicity cohort. The candidate vaccine was H5N1 A/Indonesia/05/2005 (IBCDC-RG2) adjuvanted with AS03A (tocopherol-based oil-in-water emulsion).
Figure 3.
Figure 3.
Neutralizing antibody geometric mean titers against vaccine-homologous and vaccine-heterologous strains in the neutralizing antibody set. The candidate vaccine was H5N1 A/Indonesia/05/2005 (IBCDC-RG2) adjuvanted with AS03A (tocopherol-based oil-in-water emulsion).
Figure 4.
Figure 4.
Solicited adverse events during the 7-day postvaccination period (doses 1 and 2 pooled) in the total vaccinated cohort.
See this image and copyright information in PMC

References

    1. World Health Organization. Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as pre-pandemic vaccines. http://www.who.int/csr/disease/avian_influenza/guidelines/200902_H5Vacci.... Published 2009. Accessed 15 September 2010. - PubMed
    1. Díez-Domingo J, Garcés-Sanchez M, Baldó J-M, et al. Immunogenicity and safety of H5N1 A/Vietnam/1194/2004 (clade 1) AS03-adjuvanted pre-pandemic candidate influenza vaccines in children aged 3 to 9 years: a phase II, randomized, open, controlled study. Pediatr Infect Dis J. 2010;29:e35–46. - PubMed
    1. Langley JM, Frenette L, Ferguson L, et al. Safety and cross-reactive immunogenicity of candidate AS03-adjuvanted prepandemic H5N1 influenza vaccines: a randomized controlled phase 1/2 trial in adults. J Infect Dis. 2010;201:1644–53. - PubMed
    1. Leroux-Roels I, Borkowski A, Vanwolleghem T, et al. Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial. Lancet. 2007;370:580–9. - PubMed
    1. Rumke HC, Bayas JM, de Juanes JR, et al. Safety and reactogenicity profile of an adjuvanted H5N1 pandemic candidate vaccine in adults within a phase III safety trial. Vaccine. 2008;26:2378–88. - PubMed

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