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Ten Years of Experience with the Trivalent Split-Influenza Vaccine, Fluarix™

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Abstract

Background

The trivalent inactivated split-influenza vaccine, Fluarix™, has been available since 1992.

Aim

To assess the safety and immunogenicity of the vaccine from studies in healthy adults and the elderly performed from 1992 to 2001 to comply with European Union registration requirements, and from studies in children and populations at high risk of severe influenza illness or influenza-related complications.

Methods

Annual registration studies were performed in healthy adults aged 18–60 years and the elderly aged >60 years. Six studies in children aged 6 months-18 years, and five studies in adults with high-risk conditions, were done during the same period. The high-risk populations included immunosuppressed patients with solid tumours or systemic malignancies, renal or liver transplant recipients, and patients with chronic obstructive pulmonary disease or insulin-dependent diabetes mellitus. Adults and children aged >36 months received 0.5ml of the vaccine by intramuscular or deep subcutaneous injection. Children aged 6–35 months received 0.25ml; in some children not previously vaccinated or exposed to influenza, a second dose was given 4 weeks later. Immunogenicity was determined by measuring haemagglutination inhibiting antibodies just before and 21 ± 2 days after vaccination. Redness, swelling, induration and pain at the injection site were recorded, along with systemic symptoms such as fever.

Results

In all registration studies (n = 1 558), the vaccine consistently exceeded European Union immunogenicity criteria. Geometric mean titres in adults peaked 21 days after vaccination and remained above the protection level for all three strains for up to 12 months. In healthy adults and the elderly, seroprotection rates were 69–100% and consistently exceeded 82% from 1996. Immunogenicity in children (n = 364) and high-risk populations (n = 285) exceeded the targets for healthy adults. The vaccine was well tolerated in all age groups and populations. The most frequently reported symptoms in healthy adults and the elderly were local redness of >20mm (10–31%) and swelling of >20mm (11–16%). The incidence of fever >38.5°C was <-4% in healthy adults and high-risk groups; fever of >37°C was also rare (0–5%) in children over 6 years old, but was more frequent in younger children (11–27%). The reactogenicity of the vaccine was low in the high-risk populations.

Conclusions

Fluarix™ has a good safety profile and is highly immunogenic in all age groups as well as in high-risk populations. The all-year persistence of antibodies means that the vaccine gives protection for the entire influenza season.

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Notes

  1. 1Use of tradenames is for product identification only and does not imply endorsement.

References

  1. Patriarca PA, Strikas RA. Influenza vaccine for healthy adults? N Engl J Med 1995 Oct 5; 333(14): 933–4

    Article  PubMed  CAS  Google Scholar 

  2. Potter CW. Chronicle of influenza pandemics. In: Nicholson KG, Webster RG, Hay AJ, editors. Textbook of influenza. Oxford: Blackwell Science, 1998: 3–18

    Google Scholar 

  3. World Health Organization. Influenza. WHO Information, Fact Sheet No 211 1999

  4. Nicholson KG. Human influenza. In: Nicholson KG, Webster RG, Hay AJ, editors. Textbook of influenza. Oxford: Black-well Science, 1998: 219–264

    Google Scholar 

  5. Glezen WP, Decker M, Perrotta DM. Survey of underlying conditions of persons hospitalized with acute respiratory disease during influenza epidemics in Houston, 1978–1981. Am Rev Respir Dis 1987 Sep; 136(3): 550–5

    Article  PubMed  CAS  Google Scholar 

  6. Barker WH, Mullooly JP. Pneumonia and influenza deaths during epidemics: implications for prevention. Arch Intern Med 1982 Jan; 142(1): 85–9

    Article  PubMed  CAS  Google Scholar 

  7. Lui KJ, Kendal AP. Impact of influenza epidemics on mortality in the United States from October 1972 to May 1985. Am J Public Health 1987 Jun; 77(6): 712–6

    Article  PubMed  CAS  Google Scholar 

  8. Ashley J, Smith T, Dunell K. Deaths in Great Britain associated with the influenza epidemic of 1989/90. Pop Trends 1991; 65: 16–20

    Google Scholar 

  9. Centers for Disease Control and Prevention. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2002 Apr 12; 51(RR-3): 1–31

    Google Scholar 

  10. Commission of the European Communities. Ad hoc working party on biotechnology/pharmacy ‘Harmonisation of requirements for influenza vaccines’ III/3188/91-EN. 1991

  11. Committee for Proprietary Medicinal Products (CPMP). Note for guidance on harmonisation of requirements for influenza vaccines CPMP/BWP/214/96. London: The European Agency for the Evaluation of Medicinal Products, 1997

  12. US Department of Health and Human Services. Influenza virus reagents for the hemagglutination test. Atlanta (USA): Centers for Disease Control and Prevention. Technical Service Branch, 1991

    Google Scholar 

  13. Hobson D, Baker FA, Curry RL. Effect of influenza vaccines in stimulating antibody in volunteers with prior immunity. Lancet 1973 Jul 21; II(7821): 155–6

    Article  Google Scholar 

  14. Künzel W, Glathe H, Engelmann H, et al. Kinetics of humoral antibody response to trivalent inactivated split influenza vaccine in subjects previously vaccinated or vaccinated for the first time. Vaccine 1996 Aug; 14(12): 1108–10

    Article  PubMed  Google Scholar 

  15. Van Hoecke C, Prikazsky V, Ütö I, et al. Immunogenicity of an inactivated split influenza vaccine in institutionalized elderly patients. Gerontology 1996; 42(4): 190–8

    Article  PubMed  Google Scholar 

  16. Künzel W, Engelmann H, D’Hondt E. Immune response to influenza vaccination [letter]. Lancet 1994 Jan 15; 343(8890): 173

    Article  PubMed  Google Scholar 

  17. Groothuis JR, Levin MJ, Rabalais GP, et al. Immunization of high-risk infants younger than 18 months of age with split-product influenza vaccine. Pediatrics 1991 Jun; 87(6): 823–8

    PubMed  CAS  Google Scholar 

  18. Iorio AM, Zei T, Neri M, et al. Immunization of elderly volunteers with the 1988–89 inactivated whole influenza vaccine: assessment of antibody responses by haemagglutination inhibition and single radial haemolysis tests. Eur J Epidemiol 1992 Jul; 8(4): 491–7

    Article  PubMed  CAS  Google Scholar 

  19. Glathe H, Bigl S, Grosche A. Comparison of humoral immune responses to trivalent influenza split vaccine in young, middle-aged and elderly people. Vaccine 1993; 11(7): 702–5

    Article  PubMed  CAS  Google Scholar 

  20. Van Hoecke C, Raue W, Künzel W, et al. Immunogenicity and safety of influenza vaccination in 3- to 6-year-old children with a two dose immunisation schedule. Eur J Pediatr 1996 Apr; 155(4): 346–7

    Article  PubMed  Google Scholar 

  21. Brydak LB, Machala M. Humoral immune response to influenza vaccination in patients from high risk groups. Drugs 2000 Jul; 60(1): 35–53

    Article  PubMed  CAS  Google Scholar 

  22. Kanakoudi-Tsakalidou F, Trachana M, Pratsidou-Gertsi P, et al. Influenza vaccination in children with chronic rheumatic diseases and long-term immunosuppressive therapy. Clin Exp Rheumatol 2001 Sep–Oct; 19(5): 589–94

    PubMed  CAS  Google Scholar 

  23. Brydak LB, Calbecka M. Immunogenicity of influenza vaccine in patients with hemato-oncological disorders. Leuk Lymphoma 1999 Jan; 32(3–4): 369–74

    PubMed  CAS  Google Scholar 

  24. el-Madhun AS, Cox RJ, Seime A, et al. Systemic and local immune responses after parenteral influenza vaccination in juvenile diabetic patients and healthy controls: results from a pilot study. Vaccine 1998 Jan–Feb; 16(2–3): 156–60

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

All the clinical studies reported were funded by SmithKline Beecham Biologicals (now known as GlaxoSmithKline Biologicals), Rixensart, Belgium.

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Authors and Affiliations

  1. GlaxoSmithKline Biologicals, Dresden, Germany

    Norbert W. Hehme, Walter Künzel, Frank Petschke, Gisela Türk, Carmen Raderecht &  Roland Sänger

  2. GlaxoSmithKline Biologicals, Rixensart, Belgium

    Christian van Hoecke

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  1. Norbert W. Hehme
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  2. Walter Künzel
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  3. Frank Petschke
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  4. Gisela Türk
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  6. Christian van Hoecke
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  7. Roland Sänger
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Correspondence to Roland Sänger.

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Hehme, N.W., Künzel, W., Petschke, F. et al. Ten Years of Experience with the Trivalent Split-Influenza Vaccine, Fluarix™. Clin. Drug Investig. 22, 751–769 (2002). https://doi.org/10.2165/00044011-200222110-00004

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