title: Highly Predictive Model for a Protective Immune Response to the A(H1N1)pdm2009 Influenza Strain after Seasonal Vaccination.
abstract: Understanding the immune response after vaccination against new influenza strains is highly important in case of an imminent influenza pandemic and for optimization of seasonal vaccination strategies in high risk population groups, especially the elderly. Models predicting the best sero-conversion response among the three strains in the seasonal vaccine were recently suggested. However, these models use a large number of variables and/or information post- vaccination. Here in an exploratory pilot study, we analyzed the baseline immune status in young (<31 years, N = 17) versus elderly (≥50 years, N = 20) donors sero-negative to the newly emerged A(H1N1)pdm09 influenza virus strain and correlated it with the serological response to that specific strain after seasonal influenza vaccination. Extensive multi-chromatic FACS analysis (36 lymphocyte sub-populations measured) was used to quantitatively assess the cellular immune status before vaccination. We identified CD4+ T cells, and amongst them particularly naive CD4+ T cells, as the best correlates for a successful A(H1N1)pdm09 immune response. Moreover, the number of influenza strains a donor was sero-negative to at baseline (NSSN) in addition to age, as expected, were important predictive factors. Age, NSSN and CD4+ T cell count at baseline together predicted sero-protection (HAI≥40) to A(H1N1)pdm09 with a high accuracy of 89% (p-value = 0.00002). An additional validation study (N = 43 vaccinees sero-negative to A(H1N1)pdm09) has confirmed the predictive value of age, NSSN and baseline CD4+ counts (accuracy = 85%, p-value = 0.0000004). Furthermore, the inclusion of donors at ages 31-50 had shown that the age predictive function is not linear with age but rather a sigmoid with a midpoint at about 50 years. Using these results we suggest a clinically relevant prediction model that gives the probability for non-protection to A(H1N1)pdm09 influenza strain after seasonal multi-valent vaccination as a continuous function of age, NSSN and baseline CD4 count.
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Hospital, Berlin, Germany.|Institute for Theoretical Biology, Humboldt University, Berlin, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Jürchott
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Hospital, Berlin, Germany.
authors.forename: Axel Ronald
authors.initials: AR
authors.lastname: Schulz
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Hospital, Berlin, Germany.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bozzetti
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Hospital, Berlin, Germany.
authors.forename: Dominika
authors.initials: D
authors.lastname: Pohlmann
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Hospital, Berlin, Germany.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Stervbo
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Hospital, Berlin, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Warth
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Hospital, Berlin, Germany.
authors.forename: Julia Nora
authors.initials: JN
authors.lastname: Mälzer
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Hospital, Berlin, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Waldner
authors.affiliation: Robert Koch Institute, National Reference Center for Influenza, Berlin, Germany.
authors.forename: Brunhilde
authors.initials: B
authors.lastname: Schweiger
authors.affiliation: Ivana Türbachova Laboratory for Epigentics, Epiontis GmbH, Berlin, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Olek
authors.affiliation: German Rheumatism Research Centre (DRFZ), Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Grützkau
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Hospital, Berlin, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Babel
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Hospital, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Thiel
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité University Hospital, Berlin, Germany.|Institute for Theoretical Biology, Humboldt University, Berlin, Germany.|Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.|Swiss Institute for Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
authors.forename: Avidan Uriel
authors.initials: AU
authors.lastname: Neumann
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D003198:Computer Simulation; D005858:Germany; D006801:Humans; D007113:Immunity, Innate; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008875:Middle Aged; D015233:Models, Statistical; D010865:Pilot Projects; D012621:Seasons; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines