BACKGROUND: Vaccination is the best measure to protect the population against a potential influenza H5N1 pandemic, but 2 doses of vaccine are needed to elicit protective immune responses. An immunological marker for H5N1 vaccine effectiveness is needed for early identification of the best vaccine candidate. METHODS: We conducted a phase I clinical trial of a virosomal H5N1 vaccine adjuvanted with Matrix M. Sixty adult volunteers were vaccinated intramuscularly with 2 doses of either 30 μg hemagglutinin (HA) alone or with 1.5, 7.5, or 30 μg HA and Matrix M adjuvant (50 μg). The humoral response was measured by the hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays, and the CD4(+) T-helper 1 (Th1)-cell response was measured by intracellular staining for the cytokines interleukin 2, interferon γ, and tumor necrosis factor α. RESULTS: The adjuvanted vaccine effectively induced CD4(+) Th1-cell responses, and the frequency of influenza-specific Th1 cells after the first vaccine dose predicted subsequent HI, MN, and SRH seroprotective responses after the second vaccination. CONCLUSIONS: These results support early identification of Th1-cell responses as a predictive biomarker for an efficient vaccine response, which could have great implications for early identification of persons with low or no response to vaccine when evaluating future pandemic influenza vaccines.
BACKGROUND: Vaccination is the best measure to protect the population against a potential influenza H5N1 pandemic, but 2 doses of vaccine are needed to elicit protective immune responses. An immunological marker for H5N1 vaccine effectiveness is needed for early identification of the best vaccine candidate. METHODS: We conducted a phase I clinical trial of a virosomal H5N1 vaccine adjuvanted with Matrix M. Sixty adult volunteers were vaccinated intramuscularly with 2 doses of either 30 μg hemagglutinin (HA) alone or with 1.5, 7.5, or 30 μg HA and Matrix M adjuvant (50 μg). The humoral response was measured by the hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays, and the CD4(+) T-helper 1 (Th1)-cell response was measured by intracellular staining for the cytokines interleukin 2, interferon γ, and tumor necrosis factor α. RESULTS: The adjuvanted vaccine effectively induced CD4(+) Th1-cell responses, and the frequency of influenza-specific Th1 cells after the first vaccine dose predicted subsequent HI, MN, and SRH seroprotective responses after the second vaccination. CONCLUSIONS: These results support early identification of Th1-cell responses as a predictive biomarker for an efficient vaccine response, which could have great implications for early identification of persons with low or no response to vaccine when evaluating future pandemic influenza vaccines.
Authors: Cécile van Els; Siri Mjaaland; Lisbeth Næss; Julia Sarkadi; Eva Gonczol; Karen Smith Korsholm; Jon Hansen; Jørgen de Jonge; Gideon Kersten; Jennifer Warner; Amanda Semper; Corine Kruiswijk; Fredrik Oftung Journal: Hum Vaccin Immunother Date: 2014 Impact factor: 3.452
Authors: Maikel V W van der Velden; Alexander Geisberger; Thomas Dvorak; Daniel Portsmouth; Richard Fritz; Brian A Crowe; Wolfgang Herr; Eva Distler; Eva M Wagner; Markus Zeitlinger; Robert Sauermann; Christoph Stephan; Hartmut J Ehrlich; P Noel Barrett; Gerald Aichinger Journal: Clin Vaccine Immunol Date: 2014-04-16
Authors: Larry R Smith; Walter Wodal; Brian A Crowe; Astrid Kerschbaum; Peter Bruehl; Michael G Schwendinger; Helga Savidis-Dacho; Sean M Sullivan; Mark Shlapobersky; Jukka Hartikka; Alain Rolland; P Noel Barrett; Otfried Kistner Journal: Hum Vaccin Immunother Date: 2013-03-06 Impact factor: 3.452
Authors: Peter H Goff; Tomoko Hayashi; Wenqian He; Shiyin Yao; Howard B Cottam; Gene S Tan; Brian Crain; Florian Krammer; Karen Messer; Minya Pu; Dennis A Carson; Peter Palese; Maripat Corr Journal: J Virol Date: 2017-09-12 Impact factor: 5.103