Elsevier

Vaccine

Volume 20, Issues 7–8, 15 January 2002, Pages 1240-1247
Vaccine

Safety and immunogenicity of a trivalent, inactivated, mammalian cell culture-derived influenza vaccine in healthy adults, seniors, and children

https://doi.org/10.1016/S0264-410X(01)00428-5Get rights and content

Abstract

We performed randomized, double-blind, controlled trials to assess the safety and immunogenicity of an inactivated, Madin Darby Canine Kidney (MDCK)-derived cell line produced influenza vaccine in healthy adults (19–50 years), children (3–12 years) and the elderly (≥65 years). We studied three lots of cell culture-derived vaccine and one lot of licensed egg-derived vaccine in healthy adults (n=462), two lots of cell culture-derived vaccine and one lot of egg-derived vaccine in seniors (n=269), and one lot of each vaccine in children (n=209). Adverse events were collected during the first 3 days post-immunization; serum was collected before and 1 month after immunization. Rates of local and systemic adverse reactions were similar with both vaccines. An injection site adverse event rated at least moderate severity was reported by 21.9% of children who received the egg-derived vaccine and 25.0% of those who received the cell culture-derived vaccine. In healthy adults the proportions were 12.1 and 15.3%, respectively and 6.7 and 6.3%, respectively in seniors. Systemic events of at least moderate severity were 12.4 and 12.5% in children, 19.8 and 13.6% in healthy adults, and 14.1 and 9.7% in seniors; none of these differences were statistically significant. The antibody response against all three viruses was similar between the two vaccines. From 83 to 100% of children, healthy adults and seniors achieved hemagglutination inhibition titers in excess of 40 post-immunization. We conclude that the cell culture-derived vaccine was safe and immunogenic in children, healthy adults and seniors.

Introduction

Influenza virus continues to be an important cause of respiratory infection and an important contributor to morbidity and mortality in at-risk populations including the elderly and those with underlying pulmonary conditions [1]. Although new antiviral agents have improved the ability to treat influenza infections [2], [3], immunization remains the most important method of controlling influenza through prevention [4]. As a result of the ability of the virus to modify its antigenic characteristics (antigenic drift), annual re-vaccination is required using a vaccine formulated to contain the viral strains predicted to match the strains circulating during the ensuing influenza season [5]. Although intranasal vaccines are under development [6], all currently licensed influenza vaccines are inactivated and for injection. These vaccines are all produced from viruses that are propagated in embryonated hen’s eggs. Cell culture-derived vaccines could provide substantial benefit by reducing the reliance on the supply of embryonated eggs, improving the aseptic handling of the vaccine during the manufacturing process, improving the antigenic match between the wild-type virus and the vaccine virus [7], and eliminating the risk to egg-allergic individuals [1], [8]. A bivalent cell culture-derived influenza vaccine was shown to be safe and immunogenic in healthy young adults in a phase I “first-in-human” study [9]. We report the results of three phase II studies on the safety, immunogenicity and lot consistency of a trivalent, cell culture-derived inactivated influenza vaccine in healthy adults, seniors, and children.

Section snippets

Vaccine

Two vaccines were used in these studies. The experimental vaccine was a trivalent, influenza A/B split virion vaccine prepared from virus propagated in a cell line cloned from Madin Darby Canine Kidney (MDCK) cells (cell line BV-5F1; BioChem Pharma, Sainte-Foy, Quebec, Canada) which was derived from the American Type Tissue Collection (Rockville, MD, USA). Cell lines were determined to be clonal and tested as previously described [10]. Vaccine was prepared from virus seeds (egg adapted)

Demographics

A total of 940 subjects were enrolled into the three studies including 209 children, 462 healthy adults and 269 seniors (Table 1). The mean age of the seniors was 74 years (range 65–100 years) and was 33 years (range 19–51 years) in the healthy adults. The mean age of the children was 8 years (range 3–13). One-third of healthy adults, 81.3% of seniors, and 4.3% of children reported receiving influenza vaccine in a previous year. A second immunization was given to 97 (67.4%) of the 144 children

Discussion

The results of this phase II study extend the previous phase I experience with this split virus, mammalian cell culture-derived influenza vaccine. In the phase I study, 56 healthy adult subjects were immunized with a bivalent (A/Texas/36/91 H1N1-like, B/Harbin/7/94) split virus vaccine and compared to an equal number of subjects immunized with an egg-derived vaccine [9]; a trivalent preparation was not used because of the unavailability of the third strain at the time of the study. The current

Acknowledgements

The authors would like to thank the staff of the Clinical Trials Research Center in Halifax and Saint John, the Vaccine Study Center and the Regional Home Care Program in Montreal, and Linda Houle of Houle Associates for carrying out all the clinical procedures and administering the study. We also thank the study volunteers without whom the study would not have been possible. This study was funded by BioChem Pharma, Laval, Quebec, Canada.

References (26)

  • P.B Percheson et al.

    A phase I, randomized controlled clinical trial to study the reactogenicity and immunogenicity of a new split influenza vaccine derived from a non-tumorigenic cell line

    Dev. Biol. Stand.

    (1999)
  • National Advisory Committee on Immunization. Statement on influenza vaccination for the 1998–1999 season. Can Commun...
  • Dowdle WA, Kendal AP, Noble GR. In: Lennette EH, Schmidt NJ, editors. Diagnostic procedures for viral, rickettsial and...
  • Cited by (92)

    • Inactivated Influenza Vaccines

      2017, Plotkin's Vaccines
    • Evaluation of safety and immunogenicity of HNVAC, an MDCK-based H1N1 pandemic influenza vaccine, in Phase I single centre and Phase II/III multi-centre, double-blind, randomized, placebo-controlled, parallel assignment studies

      2014, Vaccine
      Citation Excerpt :

      Pain at injection site has been the most reported AE, with the average being 25–86% in adults (18–60 years) and 14–30% in the elderly, followed by erythema, induration, swelling and bruise, being reported in 0–22% of the subjects. Systemic AEs have been reported from as low as 5% to as high as 64% of the subjects, with headache, myalgia, fatigue, and malaise being the prominent reactions, and sweating, chills, nausea and fever reported occasionally [15–27]. Several studies have also compared MDCK-derived vaccines for seasonal and H1N1 pandemic strains with those of egg-derived vaccines in clinical trials of all Phases, and have found both of them to be equally well tolerated and safe [15–18,20–22,25].

    • Inactivated influenza vaccines

      2012, Vaccines: Sixth Edition
    View all citing articles on Scopus

    Informed consent was obtained from all participants or, in the case of children, from their parents. These studies were approved by the Research Ethics Boards of the Montreal Children’s Hospital, the IWK Health Centre, the Atlantic Health Sciences Corporation, and the L’Hôpital Maisonneuve-Rosemont.

    1

    Present address: Hema-Quebec, Quebec City, Que., Canada.

    2

    Present address: Aventis Pasteur Canada, Toronto, Ont., Canada.

    View full text