Immunogenicity and safety in adults of one dose of influenza A H1N1v 2009 vaccine formulated with and without AS03A-adjuvant: Preliminary report of an observer-blind, randomised trial
Introduction
The novel, swine origin, influenza A H1N1v virus was first identified in April 2009 as the cause of human outbreaks of respiratory disease in Mexico [1]. Subsequently the emergent virus spread world-wide. As a result, on June 11, 2009 the World Health Organization (WHO) declared an influenza pandemic [2]. Widespread transmission of the virus continues and a surge in cases is expected in the Northern Hemisphere during autumn and winter [3]. This virus has a unique combination of genes from avian, human and swine strains [4], [5] and is antigenically and genetically distinct from recently circulating human influenza A H1N1 virus strains [6]. Hence much of the population less than 60 years of age may be susceptible to infection; moreover the seasonal influenza vaccines for 2009–2010 are unlikely to provide protection [7]. Vaccination is the most effective intervention to reduce morbidity and mortality during an influenza pandemic provided that vaccines are rapidly available in sufficient quantities. Here we present the first results with two pandemic H1N1v vaccines formulated with or without AS03A, an oil-in-water emulsion based adjuvant system containing tocopherol.
Seasonal influenza vaccine is usually administered as a one dose schedule. Most individuals, except young children, have been primed either by natural infection or primary vaccination and consequently, respond to a single dose of seasonal influenza vaccine. In contrast, early experience with non-adjuvanted H5N1 vaccines indicated that in a population largely naive to a new virus strain, two doses of vaccine containing high haemagglutinin (HA) antigen doses (up to 90 μg HA) are required to elicit putatively protective antibody levels [8], [9]. As such a high antigen requirement would quickly exhaust the limited global influenza antigen supply, H5N1 vaccines were formulated with adjuvants to increase immunogenicity [10], [11], [12], [13], [14], [15], [16]. AS03A was shown to significantly enhance immunogenicity of H5N1 allowing a low HA antigen level (3.75 μg) to be used [10]. In addition to this antigen sparing potential, the AS03A adjuvant system also promoted cross-immunity against drifted H5N1 strains [10], [11] and induced protection against heterologous lethal H5N1 challenge in ferrets [17]. Large safety studies [18], [19] with AS03A-adjuvanted H5N1 vaccine have indicated a clinically acceptable safety profile.
In this present study both the AS03A-adjuvanted H1N1v vaccine containing a low dose of HA and a non-adjuvanted H1N1v vaccine formulation, containing a higher dose of HA were administered according to a two dose vaccination schedule 21 days apart. This is a preliminary report on the immunogenicity and safety results following the first vaccine dose.
Section snippets
Vaccines
The monovalent A/H1N1v inactivated, split-virion vaccine was manufactured by GlaxoSmithKline (GSK) Biologicals, Dresden, Germany. The vaccine seed virus was prepared from the reassortant virus NYMC X-179A (New York Medical College, New York) generated from the A/California/7/2009 strain as recommended by WHO [20]. The seed virus was propagated on embryonated eggs and the vaccine was produced using the licensed manufacturing process for the H1N1v monovalent split-virion influenza vaccine
Study population
130 subjects were enrolled and vaccinated with a first dose of either AS03A-adjuvanted H1N1v vaccine (N = 64) or non-adjuvanted H1N1v vaccine (N = 66). The demographic profiles of the two groups were comparable with respect to mean age (39.9 ± 11.72 years and 39.3 ± 13.16 years), gender (57.8% and 53.0% male) and ethnic distribution (100% Caucasian). The two groups were also comparable with respect to seasonal influenza vaccination history with 42.2% and 39.4% of participants having received a
Discussion
As governments and public health officials prepare for mass vaccination programmes against the 2009 H1N1v pandemic strain, clinical data characterizing responses to these new vaccines are becoming available. Data from two studies in healthy adults were recently published, one conducted in Australia with a non-adjuvanted H1N1v vaccine [26] and the other in the UK with an MF59-adjuvanted H1N1v vaccine [27]. In this report we present data for both non-adjuvanted and AS03A-adjuvanted H1N1v vaccine
Acknowledgements
We are grateful to the New York Medical College, New York for providing the vaccine virus strain and to the National Institute for Biological Standards and Control (NIBSC, UK) and Therapeutic Goods Administration (TGA) from Australian Government for providing the reference standards. The authors are indebted to the participating study volunteers, clinicians, nurses and laboratory technicians at the study site as well as to the sponsor's project staff for their support and contributions
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