title: Safety and immunogenicity of a vero cell culture-derived whole-virus H5N1 influenza vaccine in chronically ill and immunocompromised patients.
abstract: The development of vaccines against H5N1 influenza A viruses is a cornerstone of pandemic preparedness. Clinical trials of H5N1 vaccines have been undertaken in healthy subjects, but studies in risk groups have been lacking. In this study, the immunogenicity and safety of a nonadjuvanted cell culture-derived whole-virus H5N1 vaccine were assessed in chronically ill and immunocompromised adults. Subjects received two priming immunizations with a clade 1 A/Vietnam H5N1 influenza vaccine, and a subset also received a booster immunization with a clade 2.1 A/Indonesia H5N1 vaccine 12 to 24 months later. The antibody responses in the two populations were assessed by virus neutralization and single radial hemolysis assays. The T-cell responses in a subset of immunocompromised patients were assessed by enzyme-linked immunosorbent spot assay (ELISPOT). The priming and the booster vaccinations were safe and well tolerated in the two risk populations, and adverse reactions were predominantly mild and transient. The priming immunizations induced neutralizing antibody titers of ≥1:20 against the A/Vietnam strain in 64.2% of the chronically ill and 41.5% of the immunocompromised subjects. After the booster vaccination, neutralizing antibody titers of ≥1:20 against the A/Vietnam and A/Indonesia strains were achieved in 77.5% and 70.8%, respectively, of chronically ill subjects and in 71.6% and 67.5%, respectively, of immunocompromised subjects. The T-cell responses against the two H5N1 strains increased significantly over the baseline values. Substantial heterosubtypic T-cell responses were elicited against the 2009 pandemic H1N1 virus and seasonal A(H1N1), A(H3N2), and B subtypes. There was a significant correlation between T-cell responses and neutralizing antibody titers. These data indicate that nonadjuvanted whole-virus cell culture-derived H5N1 influenza vaccines are suitable for immunizing chronically ill and immunocompromised populations. (This study is registered at ClinicalTrials.gov under registration no. NCT00711295.).
authors.affiliation: Vaccine R&D, Baxter BioScience, Vienna, Austria.
authors.forename: Maikel V W
authors.initials: MV
authors.lastname: van der Velden
authors.affiliation: Vaccine R&D, Baxter BioScience, Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Geisberger
authors.affiliation: Global R&D, Baxter BioScience, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dvorak
authors.affiliation: Vaccine R&D, Baxter BioScience, Orth/Donau, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Portsmouth
authors.affiliation: Vaccine R&D, Baxter BioScience, Orth/Donau, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Fritz
authors.affiliation: Vaccine R&D, Baxter BioScience, Orth/Donau, Austria.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Crowe
authors.affiliation: Department of Medicine III, University Medical Center, Mainz, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Herr
authors.affiliation: Department of Medicine III, University Medical Center, Mainz, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Distler
authors.affiliation: Department of Medicine III, University Medical Center, Mainz, Germany.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Wagner
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Sauermann
authors.affiliation: Johann Wolfgang Goethe-University Hospital, Medical Center/Infectious Diseases Unit, Frankfurt, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Stephan
authors.affiliation: Global R&D, Baxter BioScience, Vienna, Austria.
authors.forename: Hartmut J
authors.initials: HJ
authors.lastname: Ehrlich
authors.affiliation: Vaccine R&D, Baxter BioScience, Orth/Donau, Austria.
authors.forename: P Noel
authors.initials: PN
authors.lastname: Barrett
authors.affiliation: Vaccine R&D, Baxter BioScience, Vienna, Austria gerald_aichinger@baxter.com.
authors.forename: Gerald
authors.initials: G
authors.lastname: Aichinger
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D002908:Chronic Disease; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007117:Immunization, Secondary; D016867:Immunocompromised Host / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000009:adverse effects* / Q000276:immunology* / Q000627:therapeutic use; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014709:Vero Cells
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines
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