Elsevier

The Lancet

Volume 375, Issue 9708, 2–8 January 2010, Pages 49-55
The Lancet

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Safety and immunogenicity of a 2009 pandemic influenza A H1N1 vaccine when administered alone or simultaneously with the seasonal influenza vaccine for the 2009–10 influenza season: a multicentre, randomised controlled trial

https://doi.org/10.1016/S0140-6736(09)62039-0Get rights and content

Summary

Background

With the ongoing 2009 pandemic of influenza A H1N1, development of pandemic influenza vaccines has generated much interest. We investigated the safety and immunogenicity of a whole-virion, inactivated, adjuvanted pandemic H1N1 vaccine in adult and elderly volunteers, given without or simultaneously with the 2009–10 seasonal trivalent influenza vaccine.

Methods

This prospective, randomised study was undertaken in two centres in Hungary. 355 participants, including 203 adults (18–60 years) and 152 elderly people (>60 years), were assigned by stratified randomisation to either 0·5 mL of the pandemic vaccine (Fluval P, a monovalent vaccine with 6 μg haemagglutinin per 0·5 mL content and aluminium phosphate gel adjuvant; n=178) or 0·5 mL of the pandemic vaccine and 0·5 mL of the seasonal trivalent vaccine (Fluval AB, a trivalent inactivated whole-virion influenza vaccine; n=177). All vaccinations were done by specific study personnel, who did not take part in the assessment of safety or immunogenicity. Co-primary objectives were safety and immunogenicity by haemagglutinin inhibition testing. All analyses were done according to a pre-established analysis plan. This study is registered with ClinicalTrials.gov, number NCT01010893.

Findings

Two participants receiving the pandemic vaccine only (group 1) and one receiving pandemic and seasonal vaccines (group 2) were lost to follow-up. Participants in both groups developed antibody responses against the pandemic influenza A H1N1 virus (group 1: seroconversion for adults 74·3%, 95% CI 64–6–82·4 and for elderly people 61·3%, 49·1–72·4; group 2: 76·8%, 67·2–84·7 and 81·8%, 71·4–89·7, respectively). Single doses of 6 μg fulfilled European Union and US licensing criteria for interpandemic and pandemic influenza vaccines. Simultaneously, participants in group 2 developed the immune responses needed for licensing for all three seasonal strains in the seasonal vaccine for the 2009–10 season. All adverse events were rare, mild, and transient; the most frequent were pain at injection site (eight cases in group 1 vs 18 in group 2) and fatigue for 1–2 days after vaccination (three vs five cases).

Interpretation

The present pandemic vaccine is safe and immunogenic in healthy adult and elderly patients, and needs low doses and only one injection to trigger immune responses to comply with licensing criteria. It can be safely co-administered with the 2009–10 seasonal influenza vaccine.

Funding

Omninvest, Hungary.

Introduction

In April, 2009, a previously undescribed H1N1 influenza A virus was isolated from people in Mexico and the USA.1 The new strain continued to cause human infections and effectively spread between people in several countries. On June 11, 2009, a new influenza pandemic was officially declared by WHO.2 As of Sept 27, 2009, there have been more than 340 000 laboratory confirmed cases of 2009 pandemic influenza H1N1 worldwide and more than 4100 deaths reported to WHO.3 All 2009 pandemic H1N1 influenza viruses analysed so far have been antigenically and genetically similar to A/California/7/2009-like 2009 pandemic H1N1 virus.

Mass vaccination is the most effective approach to reduce illness and death from pandemic influenza. Therefore, vaccine producers are developing and assessing vaccines against pandemic H1N1 strains. Previously, we reported three clinical trials4, 5, 6 with a prepandemic influenza H5N1 vaccine and found that one dose containing only 6 μg haemagglutinin was sufficient to trigger immune responses that are needed for licensing in adult, elderly, and paediatric patients.

This study aimed to establish the safety and immunogenicity of an inactivated whole-virion vaccine against the A/California/07/2009 H1N1-like NYMC X-179A strain containing 6 μg haemagglutinin in adults and elderly people, and the safety and immunogenicity of the simultaneous administration of the seasonal influenza vaccine recommended for the 2009–10 season.

Section snippets

Participants

Between Aug 14, and Sept 15, 2009, we did a prospective, multicentre, randomised, investigator-masked trial in two centres in Hungary (State Primary Care Centres, Pilisvorosvar and Veszprem). Patients were recruited by their primary care physicians. Written informed consent was obtained from all potential participants. Negative pregnancy test on day 0 was needed for women of childbearing potential, and use of an acceptable contraception method was required for the duration of the study.

Results

The figure shows the trial profile. 368 healthy volunteers older than 18 years were screened, and 355 (203 adults aged 18–60 years and 152 elderly participants aged older than 60 years) were enrolled to receive vaccination. Every enrolled participant received vaccination as planned.

Table 1 shows demographic data of the participants. 352 patients attended the follow-up visit on day 21. Three participants did not attend the control visit: one travelled abroad during the scheduled time of the

Discussion

In this trial, one dose schedule of 6 μg of the studied pandemic H1N1 vaccine showed an encouraging immunogenic profile since it fulfilled all international licensing criteria13, 14, 15 in both the adult and elderly age-groups. Most of the global pandemic influenza strategies are based on previous work showing that at least two doses of a pandemic vaccine would be needed to elicit a protective immune response in populations who are immunologically naive to a new strain.16, 17, 18 Nonetheless,

References (25)

  • WHO

    Availability of a candidate reassortant vaccine virus for the novel influenza A (H1N1) vaccine development

  • European Directoriate for the Quality Medicines

    European Pharmacopia, 5.8 CD, 7/2007

    Strasbourg: European Directoriate for the Quality Medicines

    (2007)
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