A randomized clinical trial of an inactivated avian influenza A (H7N7) vaccine

Robert B Couch, Shital M Patel, Chianti L Wade-Bowers, Diane Niño, Robert B Couch, Shital M Patel, Chianti L Wade-Bowers, Diane Niño

Abstract

Background: Concern for a pandemic caused by a newly emerged avian influenza A virus has led to clinical trials with candidate vaccines as preparation for such an event. Most trials have involved vaccines for influenza A (H5N1), A (H7N7) or A (H9N2).

Objective: To evaluate dosage-related safety and immunogenicity of an inactivated influenza A (H7N7) vaccine in humans.

Design: One hundred twenty-five healthy young adults were randomized to receive two doses intramuscularly of placebo or 7.5, 15, 45 or 90 µg of HA of an inactivated subunit influenza A (H7N7) vaccine (25 per group), four weeks apart. Reactogenicity was evaluated closely for one week and for any adverse effect for six months after each dose. Serum hemagglutination-inhibiting and neutralizing antibody responses were determined four weeks after each dose and at six months.

Results: Reactogenicity evaluations indicated the vaccinations were well tolerated. Only one subject developed a ≥4-fold serum hemagglutination-inhibition (HAI) antibody response and a final titer of ≥1:40 four weeks after dose two and only five subjects developed a neutralizing antibody rise and a final titer of ≥1:40 in tests performed at a central laboratory. Four of the five were given the 45 or 90 µg HA dosage. A more sensitive HAI assay at the study site revealed a dose-response with increasing HA dosage but only 36% in the 90 µg HA group developed a ≥4-fold rise in antibody in this test and only one of these achieved a titer of ≥1:32.

Conclusion: This inactivated subunit influenza A (H7N7) vaccine was safe but poorly immunogenic in humans.

Trials registration: ClinicalTrials.gov NCT00546585.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Figures

Figure 1. Flow diagram of the randomized…
Figure 1. Flow diagram of the randomized clinical trial of an inactivated subunit influenza A (H7N7) vaccine.

References

    1. Webster RG, Bean WJ, Gorman OW, Chambers TM, Kawaoka Y (1992) Evolution and ecology of influenza A viruses. Microbiol Rev 56: 152–79.
    1. Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, et al. (2005) Characterization of the 1918 influenza virus polymerase genes. Nature 437: 889–93.
    1. Yen HL, Webster RG (2009) Pandemic influenza as a current threat. Curr Top Microbiol Immunol 333: 3–24.
    1. Fouchier RA, Munster V, Wallensten A, Bestebroer TM, Herfst S, et al. (2005) Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J Virol 79: 2814–2822.
    1. Tong S, Li Y, Rivailler P, Conrardy C, Castillo DA, Chen LM, et al. (2012) A distinct lineage of influenza A virus from bats. Proc Natl Acad Sci U S A 109: 4269–74.
    1. Yuen KY, Chan PKS, Peiris M, Tsang DNC, Que TL, Shortridge KF, et al. (1998) Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet 351: 467–471.
    1. Hien TT, Liem NT, Dung NT, San LT, Mai PP, van Vinh Chau N, et al. (2004) Avian influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med 350: 1179–88.
    1. Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A(H5N1) Virus (2008) Update on avian influenza A(H5N1) virus infection in humans. N Engl J Med 358: 261–273.
    1. Fouchier RA, Schneeberger PM, Rozendaal FW, Brockman JM, Kemink SA, et al. (2004) Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci USA 101: 1356–1361.
    1. Koopmans M, Wilbrink B, Conyn M, Natrop G, van der Nat H, et al. (2004) Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands. Lancet 363: 587–593.
    1. Peiris M, Yuen KY, Leung CW, Chan KH, Lai RWM, et al. (1999) Human infection with influenza H9N2. Lancet 354: 916–917.
    1. Butt KM, Smith GJD, Chen H, Zhang LJ, Leung YHC, et al. (2005) Human infection with an avian H9N2 influenza A virus in Hong Kong in 2003. J Clin Microbiol 43: 5760–5767.
    1. Jadhao SJ, Achenbach J, Swayne DE, Donis R, Cox N, et al. (2008) Development of Eurasian H7N7/PR high growth reassortant virus for clinical evaluation as an inactivated pandemic influenza vaccine. Vaccine 26: 1742–1750.
    1. Wood JM, Schild GC, Newman RW, Seagroatt V (1977) An improved single-radial-immunodiffusion technique for the assay of influenza haemagglutinin antigen: application for potency determination of inactivated whole virus and subunit vaccines. J Biol Stand 5: 237–247.
    1. Williams MS (1993) Single-radial-immunodiffusion as an in vitro potency assay for human inactivated viral vaccines. Vet Microbiol 37: 253–262.
    1. Stephenson I, Wood JM, Nicholson KG, Charlett A, Zambon MC (2004) Detection of anti-H5 responses in human sera by HI using horse erythrocytes following MF59-adjuvanted influenza A/Duck/Singapore/97 vaccine. Virus Res 103: 91–95.
    1. Rowe T, Abernathy RA, Hu-Primmer J, Thompson WW, Lu X, et al. (1999) Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays. J Clin Microbiol 37: 937–943.
    1. Couch RB, Winokur P, Brady R, Belshe R, Chen WH, et al. (2007) Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects. Vaccine 25: 7656–7663.
    1. Belser JA, Bridges CB, Katz JM, Tumpey TM (2009) Past, present, and possible future human infection with influenza virus A subtype H7. Emerg Infect Dis 15: 859–865.
    1. Hirst M, Astell CR, Griffith M, Coughlin SM, Moksa M, et al. (2004) Novel avian influenza H7N3 strain outbreak, British Columbia. Emerg Infect Dis 10: 2192–95.
    1. Tweed SA, Skowronski DM, David ST, Larder DA, Petri M, et al. (2004) Human illness from avian influenza H7N3, British Columbia. Emerg Infect Dis 10: 2196–2199.
    1. Keitel WA, Atmar RL (2009) Vaccines or pandemic influenza: summary of recent clinical trials. In: Compans RW, Orenstein WA, editors. Vaccines for pandemic influenza. Berlin Heidelberg: Springer-Verlag; pp. 431–447.
    1. Pappas C, Matsuoka Y, Swayne DE, Donis RO (2007) Development and evaluation of an influenza virus subtype H7N2 vaccine candidate for pandemic preparedness. Clin Vaccine Immunol 14: 1425–32.
    1. Itoh Y, Ozaki H, Ishigaki H, Sakoda Y, Nagata T, et al. (2010) Subcutaneous inoculation of a whole virus particle vaccine prepared from a non-pathogenic virus library induces protective immunity against H7N7 highly pathogenic avian influenza virus in cynomolgus macaques. Vaccine 28: 780–789.
    1. Min JY, Vogel L, Matsuoka Y, Lu B, Swayne D, et al. (2010) A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets, and monkeys. J Virol 84: 11950–11960.
    1. Cox RJ, Madhun AS, Hauge S, Sjursen H, Major D, et al. (2009) A phase I clinical trial of a PER.C6® cell grown influenza H7 virus vaccine. Vaccine 27: 1889–1897.
    1. Talaat KR, Karron RA, Callahan KA, Luke CJ, DiLorenzo SC, et al. (2009) A live attenuated H7N3 influenza virus vaccine is well-tolerated and immunogenic in a phase I trial in healthy adults. Vaccine 27: 3744–3753.

Source: PubMed

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