A cell culture-derived influenza vaccine provides consistent protection against infection and reduces the duration and severity of disease in infected individuals

Hartmut J Ehrlich, Julia Singer, Gregory Berezuk, Sandor Fritsch, Gerald Aichinger, Mary Kate Hart, Wael El-Amin, Daniel Portsmouth, Otfried Kistner, P Noel Barrett, Hartmut J Ehrlich, Julia Singer, Gregory Berezuk, Sandor Fritsch, Gerald Aichinger, Mary Kate Hart, Wael El-Amin, Daniel Portsmouth, Otfried Kistner, P Noel Barrett

Abstract

Background: Current knowledge of the consistency of protection induced by seasonal influenza vaccines over the duration of a full influenza season is limited, and little is known about the clinical course of disease in individuals who become infected despite vaccination.

Methods: Data from a randomized double-blind placebo-controlled clinical trial undertaken in healthy young adults in the 2008-2009 influenza season were used to investigate the weekly cumulative efficacy of a Vero cell culture-derived influenza vaccine. In addition, the duration and severity of disease in vaccine and placebo recipients with cell culture-confirmed influenza infection were compared.

Results: Vaccine efficacy against matching strains was consistently high (73%-82%) throughout the study, including the entire period of the influenza season during which influenza activity was above the epidemic threshold. Vaccine efficacy was also consistent (68%-83%) when calculated for all strains, irrespective of antigenic match. Vaccination also ameliorated disease symptoms when infection was not prevented. Bivariate analysis of duration and severity showed a significant amelioration of myalgia (P = .003), headache (P = .025), and fatigue (P = .013) in infected vaccinated subjects compared with placebo. Cough (P = .143) and oropharyngeal pain (P = .083) were also reduced in infected vaccinated subjects.

Conclusions: A Vero cell culture-derived influenza vaccine provides consistently high levels of protection against cell culture-confirmed infection by seasonal influenza virus and significantly reduces the duration and severity of disease in those individuals in which infection is not prevented.

Clinical trials registration: ClinicalTrials.gov NCT00566345.

Figures

Figure 1.
Figure 1.
Flow of participants through the study. Abbreviation: VCIV, Vero cell culture–derived influenza vaccine.
Figure 2.
Figure 2.
Weekly cumulative vaccine efficacy against cell culture–confirmed influenza infection. Vaccine efficacy could be calculated from 24 January 2009, ∼6 weeks after vaccination of the last subject on 15 December. Analysis of specimens from influenzalike illness visits continued until 15 May; the last laboratory-confirmed influenza infection was recorded in the week ending 9 May 2009.
Figure 3.
Figure 3.
Amelioration of disease symptoms in subjects with cell culture–confirmed influenza infection. Symptoms are rated as severe (red), moderate (orange), or mild (green). aFour placebo recipients had cough for >20 days. Three were rated as moderate (31, 35, and 51 days duration), and 1 was rated as severe (22 days duration). bOne recipient of Vero cell culture–derived influenza vaccine had oropharyngeal pain for 31 days, rated moderate. Abbreviation: VCIV, Vero cell culture--derived influenza vaccine.

References

    1. Barrett PN, Berezuk G, Fritsch S, et al. Efficacy, safety, and immunogenicity of a Vero-cell-culture-derived trivalent influenza vaccine: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2011;377:751–9.
    1. Frey S, Vesikari T, Szymczakiewicz-Multanowska A, et al. Clinical efficacy of cell culture-derived and egg-derived inactivated subunit influenza vaccines in healthy adults. Clin Infect Dis. 2010;51:997–1004.
    1. Monto AS, Ohmit SE, Petrie JG, et al. Comparative efficacy of inactivated and live attenuated influenza vaccines. N Engl J Med. 2009;361:1260–7.
    1. Beran J, Vesikari T, Wertzova V, et al. Efficacy of inactivated split-virus influenza vaccine against culture-confirmed influenza in healthy adults: a prospective, randomized, placebo-controlled trial. J Infect Dis. 2009;200:1861–9.
    1. Ohmit SE, Victor JC, Rotthoff JR, et al. Prevention of antigenically drifted influenza by inactivated and live attenuated vaccines. N Engl J Med. 2006;355:2513–22.
    1. Beran J, Wertzova V, Honegr K, et al. Challenge of conducting a placebo-controlled randomized efficacy study for influenza vaccine in a season with low attack rate and a mismatched vaccine B strain: a concrete example. BMC Infect Dis. 2009;9:2.
    1. Nichol KL. Heterogeneity of influenza case definitions and implications for interpreting and comparing study results. Vaccine. 2006;24:6726–8.
    1. Miettinen O, Nurminen M. Comparative analysis of two rates. Stat Med. 1985;4:213–26.
    1. Hothorn T, Hornik K, van de Wiel MA, Zeileis A. A Lego system for conditional inference. Am Stat. 2006;60:257–63.
    1. CDC. Update: influenza activity—United States, September 28, 2008–April 4, 2009, and composition of the 2009–10 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2009;58:369–74.
    1. CDC. Key facts about influenza (flu) and flu vaccine. Available at: . Accessed 23 August 2011.
    1. Foy HM, Cooney MK, McMahan R, Bor E, Grayston JT. Single-dose monovalent A2-Hong Kong influenza vaccine: Efficacy 14 months after immunization. JAMA. 1971;217:1067–71.
    1. Foy HM, Cooney MK, McMahan R. A Hong Kong influenza immunity three years after immunization. JAMA. 1973;226:758–61.
    1. Clark A, Potter CW, Jennings R, et al. A comparison of live and inactivated influenza A (H1N1) virus vaccines: 2. Long-term immunity. J Hyg (Lond) 1983;90:361–70.
    1. Ambrose CS, Yi T, Walker RE, Connor EM. Duration of protection provided by live attenuated influenza vaccine in children. Pediatr Infect Dis J. 2008;27:744–8.
    1. Ambrose CS, Wu X, Belshe RB. The efficacy of live attenuated and inactivated influenza vaccines in children as a function of time postvaccination. Pediatr Infect Dis J. 2010;29:806–11.
    1. Jackson LA, Gaglani MJ, Keyserling HL, et al. Safety, efficacy, and immunogenicity of an inactivated influenza vaccine in healthy adults: a randomized, placebo-controlled trial over two influenza seasons. BMC Infect Dis. 2010;10:71.
    1. Ohmit SE, Victor JC, Teich ER, et al. Prevention of symptomatic seasonal influenza in 2005–2006 by inactivated and live attenuated vaccines. J Infect Dis. 2008;198:312–17.
    1. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12:36–44.
    1. Jefferson T, Di Pietrantonj C, Rivetti A, Bawazeer GA, Al-Ansary LA, Ferroni E. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2010 (7):CD001269.
    1. Kamada M, Nagai T, Kumagai T, et al. Efficacy of inactivated trivalent influenza vaccine in alleviating the febrile illness of culture-confirmed influenza in children in the 2000–2001 influenza season. Vaccine. 2006;24:3618–23.
    1. Belshe RB, Mendelman PM, Treanor J, et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine in children. N Engl J Med. 1998;338:1405–12.
    1. Yang CF, Belshe RB, Kemble G, et al. Genetic sequence analysis of influenza viruses and illness severity in ill children previously vaccinated with live attenuated or inactivated influenza vaccine. Vaccine. 2010;28:5128–34.
    1. Forrest BD, Steele AD, Hiemstra L, Rappaport R, Ambrose CS, Gruber WC. A prospective, randomized, open-label trial comparing the safety and efficacy of trivalent live attenuated and inactivated influenza vaccines in adults 60 years of age and older. Vaccine. 2011;29:3633–9.
    1. Block SL, Heikkinen T, Toback SL, Zheng W, Ambrose CS. The efficacy of live attenuated influenza vaccine against influenza-associated acute otitis media in children. Pediatr Infect Dis J. 2011;30:203–7.
    1. Clements ML, Betts RF, Murphy BR. Advantage of live attenuated cold-adapted influenza A virus over inactivated vaccine for A/Washington/80 (H3N2) wild-type virus infection. Lancet. 1984;1:705–8.
    1. Clements ML, Murphy BR. Development and persistence of local and systemic antibody responses in adults given live attenuated or inactivated influenza A virus vaccine. J Clin Microbiol. 1986;23:66–72.
    1. Sears SD, Clements ML, Betts RF, Maassab HF, Murphy BR, Snyder MH. Comparison of live, attenuated H1N1 and H3N2 cold-adapted and avian-human influenza A reassortant viruses and inactivated virus vaccine in adults. J Infect Dis. 1988;158:1209–19.
    1. Nichol KL, Lind A, Margolis KL, et al. The effectiveness of vaccination against influenza in healthy, working adults. N Engl J Med. 1995;333:889–93.
    1. Nichol KL, Mallon KP, Mendelman PM. Cost benefit of influenza vaccination in healthy, working adults: an economic analysis based on the results of a clinical trial of trivalent live attenuated influenza virus vaccine. Vaccine. 2003;21:2207–17.
    1. Molinari NA, Ortega-Sanchez IR, Messonnier ML, et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine. 2007;25:5086–96.
    1. Fiore AE, Uyeki TM, Broder K, et al. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Recomm Rep. 2010;59:1–62.
    1. US Department of Health and Human Services. Healthy people 2020: topics and objectives index. Available at: . Accessed 23 August 2011.
    1. Barrett PN, Mundt W, Kistner O, Howard MK. Vero cell platform in vaccine production: moving towards cell culture–based viral vaccines. Expert Rev Vaccines. 2009;8:607–18.
    1. Glezen WP. Cell-culture-derived influenza vaccine production. Lancet. 2011;377:698–700.

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