Clinical trial to evaluate the safety and immunogenicity of a trivalent surface antigen seasonal influenza vaccine produced in mammalian cell culture and administered to young and elderly adults with and without A(H1N1) pre-vaccination

PLoS One. 2013 Aug 16;8(8):e70866. doi: 10.1371/journal.pone.0070866. eCollection 2013.

Abstract

Vaccination against influenza is an important means of reducing morbidity and mortality in subjects at risk. The prevalent viral strains responsible for seasonal epidemics usually change annually, but the WHO recommendations for the 2011/2012-season in the Northern hemisphere included the same antigens as for the previous season. We conducted a single-center, single-arm study involving 62 younger (18-60 years) and 64 older (>60 years) adults to test the immunogenicity, safety and tolerability of a trivalent surface antigen, inactivated influenza vaccine produced in mammalian cell-culture. The vaccine contained 15 µg hemagglutinin of each of the virus strains recommended for the 2011-2012 Northern hemisphere winter season (A/California/7/09 (H1N1)-; A/Perth/16/09 (H3N2)-; B/Brisbane/60/08-like strain) in a non-adjuvanted preservative-free formulation. Antibody response was measured by hemagglutination inhibition 21 days after immunization. Adverse events and safety were assessed using subject diary cards and telephone interviews. Seroconversion or a 4-fold antibody increase in antibody titers was detectable against A(H1N1) in 68% of both younger and older adults, against A(H3N2) in 53% and 27%, and against the B influenza strain in 35% and 17%. Antibody titers of 40 or more were observed against A(H1N1) in 87% and 90% of younger and older adults, against A(H3N2) in 98% and 98%, and against the B influenza strain in 93% and 90%. Pre-vaccination antibody titers were protective against A(H1N1), A(H3N2) and B in 38%, 58% and 58%, respectively, of younger and in 43%, 88% and 70% of older adults. Among subjects with previous A(H1N1) vaccination only 48% of younger and 47% of older adults had protective A(H1N1) antibodies at inclusion. Adverse reactions were generally mild. The most frequently reported reactions were pain at the injection site, myalgia and fatigue. The vaccine generated protective antibodies against all three viral strains and had an acceptable safety profile in both younger and older adults.

Trial registration: ClinicalTrials.govNCT01422512.

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Viral / blood*
  • Female
  • Hemagglutination Inhibition Tests
  • Hemagglutinins, Viral / immunology
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A Virus, H3N2 Subtype / immunology*
  • Influenza B virus / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Influenza, Human / blood
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Male
  • Middle Aged
  • Seasons
  • Vaccination / methods*
  • Vaccines, Subunit

Substances

  • Antibodies, Viral
  • Hemagglutinins, Viral
  • Influenza Vaccines
  • Vaccines, Subunit

Associated data

  • ClinicalTrials.gov/NCT01422512

Grants and funding

This study was funded by Novartis Vaccines. The funders had no role in data collection and the decision to publish, or the preparation of the manuscript. The study was designed according to the Committee for Medicinal Products for Human Use (CHMP) by the sponsor. The decision in the writing of this report and to submit the paper for publication was solely made by the study team at the University of Rostock. All authors have made substantial contributions to this study approval of the version submitted. Financial Disclosures: DB and SM are employees of the sponsor; all other authors declare that no competing interests exist. No current external funding sources for this study.