Daniel F Hoft1, Kathleen Lottenbach1, Johannes B Goll2, Heather Hill2, Patricia L Winokur3, Shital M Patel4, Rebecca C Brady5, Wilbur H Chen6, Kathryn Edwards7, C Buddy Creech7, Sharon E Frey1, Tamara P Blevins1, Rachelle Salomon8, Robert B Belshe1. 1. Department of Internal Medicine, Saint Louis University, Missouri. 2. Emmes Corporation, Rockville. 3. Department of Internal Medicine, University of Iowa and Iowa City VA Healthcare System. 4. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas. 5. Gamble Program for Clinical Studies, Cincinnati Children's Hospital, Ohio. 6. Center for Vaccine Development, University of Maryland School of Medicine, Baltimore. 7. Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University, Nashville, Tennessee. 8. Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Abstract
BACKGROUND: Influenza A(H5N1) virus and other avian influenza virus strains represent major pandemic threats. Like all influenza A virus strains, A(H5N1) viruses evolve rapidly. Innovative immunization strategies are needed to induce cross-protective immunity. METHODS: Subjects primed with clade 1 H5 antigen, with or without adjuvant, and H5-naive individuals were boosted with clade 2 H5 antigen. The impact of priming on T cells capable of both proliferation and cytokine production after antigen restimulation was assessed. RESULTS: Subjects previously vaccinated with clade 1 H5 antigen developed significantly enhanced clade 2 H5 cross-reactive T cell responses detectable 6 months after vaccination with clade 2 H5 antigen. Priming dose (15 µg vs 45 or 90 µg) had no effect on magnitude of heterotypic H5 T cell responses. In contrast, age at priming negatively modulated both the magnitude and duration of heterotypic H5 T cell responses. Elderly subjects developed significantly less heterotypic H5 T cell boosting, predominantly for T cells capable of cytokine production. Adjuvant had a positive albeit weaker effect than age. The magnitude of CD4(+) interferon-γ producing T cells correlated with H5 antibody responses. CONCLUSIONS: H5 heterotypic priming prior to onset of an A(H5N1) pandemic may increase magnitude and duration of immunity against a newly drifted pandemic H5 virus.
BACKGROUND:Influenza A(H5N1) virus and other avian influenza virus strains represent major pandemic threats. Like all influenza A virus strains, A(H5N1) viruses evolve rapidly. Innovative immunization strategies are needed to induce cross-protective immunity. METHODS: Subjects primed with clade 1 H5 antigen, with or without adjuvant, and H5-naive individuals were boosted with clade 2 H5 antigen. The impact of priming on T cells capable of both proliferation and cytokine production after antigen restimulation was assessed. RESULTS: Subjects previously vaccinated with clade 1 H5 antigen developed significantly enhanced clade 2 H5 cross-reactive T cell responses detectable 6 months after vaccination with clade 2 H5 antigen. Priming dose (15 µg vs 45 or 90 µg) had no effect on magnitude of heterotypic H5 T cell responses. In contrast, age at priming negatively modulated both the magnitude and duration of heterotypic H5 T cell responses. Elderly subjects developed significantly less heterotypic H5 T cell boosting, predominantly for T cells capable of cytokine production. Adjuvant had a positive albeit weaker effect than age. The magnitude of CD4(+) interferon-γ producing T cells correlated with H5 antibody responses. CONCLUSIONS: H5 heterotypic priming prior to onset of an A(H5N1) pandemic may increase magnitude and duration of immunity against a newly drifted pandemic H5 virus.
Authors: Tom M Wilkinson; Chris K F Li; Cecilia S C Chui; Arthur K Y Huang; Molly Perkins; Julia C Liebner; Rob Lambkin-Williams; Anthony Gilbert; John Oxford; Ben Nicholas; Karl J Staples; Tao Dong; Daniel C Douek; Andrew J McMichael; Xiao-Ning Xu Journal: Nat Med Date: 2012-01-29 Impact factor: 53.440
Authors: J B Ulmer; T M Fu; R R Deck; A Friedman; L Guan; C DeWitt; X Liu; S Wang; M A Liu; J J Donnelly; M J Caulfield Journal: J Virol Date: 1998-07 Impact factor: 5.103
Authors: Wendy A Keitel; Cornelia L Dekker; ChrisAnna Mink; James D Campbell; Kathryn M Edwards; Shital M Patel; Dora Y Ho; Helen K Talbot; Kuo Guo; Diana L Noah; Heather Hill Journal: Vaccine Date: 2009-03-25 Impact factor: 3.641
Authors: Rafael A Medina; Balaji Manicassamy; Silke Stertz; Christopher W Seibert; Rong Hai; Robert B Belshe; Sharon E Frey; Christopher F Basler; Peter Palese; Adolfo García-Sastre Journal: Nat Commun Date: 2010-06-15 Impact factor: 14.919
Authors: Andrea J Sant; Anthony T DiPiazza; Jennifer L Nayak; Ajitanuj Rattan; Katherine A Richards Journal: Immunol Rev Date: 2018-07 Impact factor: 12.988
Authors: Rie Nakajima; Medalyn Supnet; Algis Jasinskas; Aarti Jain; Omid Taghavian; Joshua Obiero; Donald K Milton; Wilbur H Chen; Michael Grantham; Richard Webby; Florian Krammer; Darrick Carter; Philip L Felgner; D Huw Davies Journal: mSphere Date: 2018-12-12 Impact factor: 4.389
Authors: Gabriela Tapia-Calle; Philip A Born; Georgia Koutsoumpli; Martin Ignacio Gonzalez-Rodriguez; Wouter L J Hinrichs; Anke L W Huckriede Journal: Vaccines (Basel) Date: 2019-11-13