Giuseppe
Emeritus
[Source: The Journal of Infectious Diseases, full text: (LINK). Abstract, edited.]
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DNA priming prior to H5N1 inactivated influenza vaccination expands antibody epitope repertoire and increases affinity maturation in a boost-interval-dependent manner in adults
Surender Khurana 1,*, Jian Wu 1, Milena Dimitrova 1, Lisa R. King 1, Jody Manischewitz 1, Barney S. Graham 2, Julie E. Ledgerwood 2 and Hana Golding 1,*
Author Affiliations: <SUP>1</SUP>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration <SUP>2</SUP>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
*To whom correspondence should be addressed: Surender Khurana, Phone: 301-827-0739; Fax: 301-496-1810; Email: Surender.Khurana@fda.hhs.gov, Hana Golding, Phone: 301-827-0784; Fax: 301-496-1810; Email: Hana.golding@fda.hhs.gov
Abstract
DNA priming improves response to inactivated H5N1 vaccination. We assessed the immunogenicity of H5 DNA (A/Indonesia/5/2005) followed by H5N1 monovalent inactivated vaccine (MIV) boost at 4, 8, 12, 16, and 24 weeks compared to two-doses of H5N1 MIV in adults. Antibody epitope repertoires were elucidated by Genome-Fragment-Phage-Display-Library, and antibody avidities for HA1 and HA2 domains were measured by Surface Plasmon Resonance. H5 DNA priming expanded H5-specific antibody epitope repertoire and enhanced antibody avidity to the HA1 (but not HA2) domain, in interval-dependent manner. Enhanced HA1-binding and avidity (≥12 wk interval) correlated with improved neutralization of homologous and heterologous H5N1 strains.
Received November 27, 2012. Revision received January 31, 2013. Accepted February 6, 2013.
Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2013.
-Surender Khurana 1,*, Jian Wu 1, Milena Dimitrova 1, Lisa R. King 1, Jody Manischewitz 1, Barney S. Graham 2, Julie E. Ledgerwood 2 and Hana Golding 1,*
Author Affiliations: <SUP>1</SUP>Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration <SUP>2</SUP>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
*To whom correspondence should be addressed: Surender Khurana, Phone: 301-827-0739; Fax: 301-496-1810; Email: Surender.Khurana@fda.hhs.gov, Hana Golding, Phone: 301-827-0784; Fax: 301-496-1810; Email: Hana.golding@fda.hhs.gov
Abstract
DNA priming improves response to inactivated H5N1 vaccination. We assessed the immunogenicity of H5 DNA (A/Indonesia/5/2005) followed by H5N1 monovalent inactivated vaccine (MIV) boost at 4, 8, 12, 16, and 24 weeks compared to two-doses of H5N1 MIV in adults. Antibody epitope repertoires were elucidated by Genome-Fragment-Phage-Display-Library, and antibody avidities for HA1 and HA2 domains were measured by Surface Plasmon Resonance. H5 DNA priming expanded H5-specific antibody epitope repertoire and enhanced antibody avidity to the HA1 (but not HA2) domain, in interval-dependent manner. Enhanced HA1-binding and avidity (≥12 wk interval) correlated with improved neutralization of homologous and heterologous H5N1 strains.
Received November 27, 2012. Revision received January 31, 2013. Accepted February 6, 2013.
Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2013.
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