J Korean Med Sci.  2011 Nov;26(11):1421-1427. 10.3346/jkms.2011.26.11.1421.

Safety and Immunogenicity of a New Trivalent Inactivated Split-virus Influenza Vaccine in Healthy Korean Children: A Randomized, Double-blinded, Active-controlled, Phase III Study

• Kang JH
• Oh CE
• Lee J
• Lee SY
• Cha SH
• Kim DS
• Kim HH
• Lee JH
• Kim JT
• Ma SH
• Hong YJ
• Cheong HJ
• Lee HJ

• KMID: 1123441
• DOI: http://doi.org/10.3346/jkms.2011.26.11.1421

Abstract

We report results of a randomized, double-blinded, active-controlled, phase III study conducted to evaluate the immunogenicity and safety of a new trivalent inactivated split-virus influenza vaccine (GC501) manufactured by the Green Cross Corporation in Korea. A total of 283 healthy children aged 6 months to < 18 yr were randomized to receive either GC501 or control. Of the GC501 recipients, seroconversion occurred in 48.5% for A/H1N1, 67.7% for A/H3N2 and 52% for influenza B. The proportion of subjects who had post-vaccination hemagglutination-inhibition titers of 1:40 or greater was 90.7% for A/H1N1, 86.8% for A/H3N2 and 82.4% for influenza B in the GC501 recipients. No serious adverse events related to vaccination, or withdrawals because of adverse events were reported. The majority of solicited adverse events were mild in intensity. GC501 vaccine has good tolerability and favorable immunogenicity in children aged 6 months to < 18 yr. The addition of one more brand of influenza vaccine may allow for better global accessibility of vaccine for epidemics or future pandemics.

Keyword

Influenza Vaccines; Child; Immunogenicity; Safety

MeSH Terms

Adolescent
Antibodies, Viral/*blood
Child
Child, Preschool
Double-Blind Method
Female
Humans
Infant
Influenza A Virus, H1N1 Subtype/*immunology
Influenza A Virus, H3N2 Subtype/*immunology
Influenza B virus/*immunology
Influenza Vaccines/*adverse effects/*immunology
Male
Republic of Korea
Vaccination
Vaccines, Inactivated/adverse effects/immunology

Figure

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  Fig. 1 Enrollment and follow-up of the study subjects.

Reference

1. Miller E, Hoschler K, Hardelid P, Stanford E, Andrews N, Zambon M. Incidence of 2009 pandemic influenza A H1N1 infection in England: a cross-sectional serological study. Lancet. 2010. 375:1100–1108.

2. Monto AS, Kioumehr F. The Tecumseh Study of Respiratory Illness. IX. Occurence of influenza in the community, 1966-1971. Am J Epidemiol. 1975. 102:553–563.

3. Basta NE, Chao DL, Halloran ME, Matrajt L, Longini IM Jr. Strategies for pandemic and seasonal influenza vaccination of schoolchildren in the United States. Am J Epidemiol. 2009. 170:679–686.

4. Macroepidemiology of Influenza Vaccination (MIV) Study Group. The macro-epidemiology of influenza vaccination in 56 countries, 1997-2003. Vaccine. 2005. 23:5133–5143.

5. Song JY, Cheong HJ, Woo HJ, Wie SH, Lee JS, Chung MH, Kim YR, Jung SI, Park KH, Kim TH, Uh ST, Kim WJ. Immunogenicity and safety of trivalent inactivated influenza vaccine: a randomized, double-blind, multicenter, phase 3 clinical trial in a vaccine-limited country. J Korean Med Sci. 2011. 26:191–195.

6. Fiore AE, Uyeki TM, Broder K, Finelli L, Euler GL, Singleton JA, Iskander JK, Wortley PM, Shay DK, Bresee JS, Cox NJ. Centers for Disease Control and Prevention. Prevention and control of influenza with vaccines, recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Recomm Rep. 2010. 59:1–62.

7. Guidance for industry: toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research. 2007. accessed on April 15, 2011. Available at http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Giuidances/Vaccines/ucm074775.htm.

8. Hannoun C, Megas F, Piercy J. Immunogenicity and protective efficacy of influenza vaccination. Virus Res. 2004. 103:133–138.

9. Song JY, Cheong HJ, Hwang IS, Choi WS, Jo YM, Park DW, Cho GJ, Hwang TG, Kim WJ. Long-term immunogenicity of influenza vaccine among the elderly: risk factors for poor immune response and persistence. Vaccine. 2010. 28:3929–3935.

10. Guidance for industry: clinical data needed to support the licensure of seasonal inactivated influenza vaccines. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research. 2007. accessed on April 15, 2011. Available at http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/ucm091985.pdf.

11. The global action plan for influenza vaccines. World Health Organization. accessed on August 05, 2011. Available at http://www.who.int/influenza_vaccines_plan/resources/5report_gap_ag_5may11.pdf.

12. Neuzil K, Jackson L, Nelson J, Klimov A, Cox N, Bridges C, Dunn J, DeStefano F, Shay D. Immunogenicity and reactogenicity of 1 versus 2 doses of trivalent inactivated influenza vaccine in vaccine-naive 5-8-year-old children. J Infect Dis. 2006. 194:1032–1039.

13. Englund JA, Walter EB, Fairchok MP, Monto AS, Neuzil KM. A comparison of 2 influenza vaccine schedules in 6- to 23-month-old children. Pediatrics. 2005. 115:1039–1047.

14. Note for guidance on harmonisation of requirements for influenza vaccines (CPMP/BWP/214/96). Committee for Proprietary Medicinal Products. 1997. March. accessed on April 15, 2011. The European Agency for the Evaluation of Medicinal Products;Available at http://www.ema.europa.eu/pdfs/human/bwp/021496en.pdf.

15. Ruben FL. Inactivated influenza virus vaccines in children. Clin Infect Dis. 2004. 38:678–688.

16. Kanra G, Marchisio P, Feiterna-Sperling C, Gaedicke G, Lazar H, Durrer P, Kürsteiner O, Herzog C, Kara A, Principi N. Comparison of immunogenicity and tolerability of a virosome-adjuvanted and a split influenza vaccine in children. Pediatr Infect Dis J. 2004. 23:300–306.

17. Gonzalez M, Pirez MC, Ward E, Dibarboure H, García A, Picolet H. Safety and immunogenicity of a paediatric presentation of an influenza vaccine. Arch Dis Child. 2000. 83:488–491.

18. Hoberman A, Greenberg DP, Paradise JL, Rockette HE, Lave JR, Kearney DH, Colborn DK, Kurs-Lasky M, Haralam MA, Byers CJ, Zoffel LM, Fabian IA, Bernard BS, Kerr JD. Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. JAMA. 2003. 290:1608–1616.