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H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.

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Date
2011-01
Authors
Moody, M Anthony
Zhang, Ruijun
Walter, Emmanuel B
Woods, Christopher W
Ginsburg, Geoffrey S
McClain, Micah T
Denny, Thomas N
Chen, Xi
Munshaw, Supriya
Marshall, Dawn J
Whitesides, John F
Drinker, Mark S
Amos, Joshua D
Gurley, Thaddeus C
Eudailey, Joshua A
Foulger, Andrew
DeRosa, Katherine R
Parks, Robert
Meyerhoff, R Ryan
Yu, Jae-Sung
Kozink, Daniel M
Barefoot, Brice E
Ramsburg, Elizabeth A
Khurana, Surender
Golding, Hana
Vandergrift, Nathan A
Alam, S Munir
Tomaras, Georgia D
Kepler, Thomas B
Kelsoe, Garnett
Liao, Hua-Xin
Haynes, Barton F
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Abstract
During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection.To study hemagglutinin (HA) antibody responses in influenza immunization and infection, we have studied the day 7 plasma cell repertoires of subjects immunized with seasonal trivalent inactivated influenza vaccine (TIV) and compared them to the plasma cell repertoires of subjects experimentally infected (EI) with influenza H3N2 A/Wisconsin/67/2005. The majority of circulating plasma cells after TIV produced influenza-specific antibodies, while most plasma cells after EI produced antibodies that did not react with influenza HA. While anti-HA antibodies from TIV subjects were primarily reactive with single or few HA strains, anti-HA antibodies from EI subjects were isolated that reacted with multiple HA strains. Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects. From an H3N2-infected subject, we isolated a 4-member clonal lineage of broadly cross-reactive antibodies that bound to multiple HA subtypes and neutralized both H1N1 and H3N2 viruses. This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject.The presence of broadly reactive subdominant antibody responses in some EI subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains.
Type
Journal article
Subject
Humans
Hemagglutinin Glycoproteins, Influenza Virus
Influenza Vaccines
Antibodies, Viral
Fluorescent Antibody Technique, Indirect
Enzyme-Linked Immunosorbent Assay
Surface Plasmon Resonance
Reverse Transcriptase Polymerase Chain Reaction
Antibody Specificity
Cross Reactions
Influenza, Human
Influenza A Virus, H3N2 Subtype
Permalink
https://hdl.handle.net/10161/22006
Published Version (Please cite this version)
10.1371/journal.pone.0025797
Publication Info
Moody, M Anthony; Zhang, Ruijun; Walter, Emmanuel B; Woods, Christopher W; Ginsburg, Geoffrey S; McClain, Micah T; ... Haynes, Barton F (2011). H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination. PloS one, 6(10). pp. e25797. 10.1371/journal.pone.0025797. Retrieved from https://hdl.handle.net/10161/22006.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Alam

S. Munir Alam

Professor in Medicine
Research Interests.  The Alam laboratory’s primary research is focused on understanding the biophysical properties of antigen-antibody binding and the molecular events of early B cell activation using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events for their activation. In the lon
Denny

Thomas Norton Denny

Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor of Medicine in the Department of Medicine at Duke University Medical Center. He is also an Affiliate Member of the Duke Global Health Institute. Previously, he served on the Health Sector Advisory Council of the Duke University Fuquay School of Business. Prior to joining Duke, he was an Associate Professor of Pathology, Labo
Ginsburg

Geoffrey Steven Ginsburg

Adjunct Professor in the Department of Medicine
Dr. Geoffrey S. Ginsburg's research interests are in the development of novel paradigms for developing and translating genomic information into medical practice and the integration of personalized medicine into health care.
Haynes

Barton Ford Haynes

Frederic M. Hanes Distinguished Professor of Medicine
Barton F. Haynes, M.D. is the Frederic M. Hanes Professor of Medicine and Immunology, and Director of the Duke Human Vaccine Institute. Prior to leading the DHVI, Dr. Haynes served as Chief of the Division of Rheumatology, Allergy and Clinical Immunology, and later as Chair of the Department of Medicine. As Director of the Duke Human Vaccine Institute, Bart Haynes is leading a team of investigators working on vaccines for emerging infections, including tuberculosis, pandemic influenza, emergi
Kelsoe

Garnett H. Kelsoe

James B. Duke Distinguished Professor of Immunology
1. Lymphocyte development and antigen-driven diversification of immunoglobulin and T cell antigen receptor genes. 2. The germinal center reaction and mechanisms for clonal selection and self - tolerance. The origins of autoimmunity. 3. Interaction of innate- and adaptive immunity and the role of inflammation in lymphoid organogenesis. 4. The role of secondary V(D)J gene rearrangment in lymphocyte development and malignancies. 5. Mathematical modeling of immune responses,
Liao

Hua-Xin Liao

Adjunct Professor in the Department of Medicine
Dr. Liao is a Professor of Medicine and Research Director of Duke Human Vaccine Institute. Dr. Liao is a MD virologistt rained in China. In early 1980’s, Dr. Liao made major contributions to the first isolation of epidemic hemorrhagic fever virus (hataanvirus) from Apodemus agraius using tissue culture in China. The successful identification and isolation of Hataanvirus enabled the early diagnosis and treatment of the disease, and advancement of HFRS research towards prevention by de
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
McClain

Micah Thomas McClain

Associate Professor of Medicine
Meyerhoff

Ryan Meyerhoff

House Staff
Program Start Year:  2013Barton Haynes Laboratory"Studies of Immunogens to Induce Broadly Neutralizing HIV Antibodies"
Moody

Michael Anthony Moody

Professor of Pediatrics
Tony Moody, MD is a Professor in the Department of Pediatrics, Division of Infectious Diseases and Professor in the Department of Integrative Immunobiology at Duke University Medical Center. Research in the Moody lab is focused on understanding the B cell responses during infection, vaccination, and disease. The lab has become a resource for human phenotyping, flow characterization, staining and analysis at the Duke Human Vaccine Institute (DHVI). The Moody lab is currently funded to study in

Elizabeth Anne Ramsburg

Adjunct Assistant Professor in the Department of Molecular Genetics and Microbiology
In principle, most viral infections can be prevented by effective and timely vaccination. In the past several decades however, the rapid emergence and spread into new geographical areas of viruses such as dengue, West Nile virus, HIV, and the highly pathogenic avian influenzas has outpaced the development of preventative vaccines. The major focus of research in the Ramsburg lab is to develop novel vaccines based on recombinant viruses for the prevention of viral diseases, and to better char
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
Tomaras

Georgia Doris Tomaras

Professor in Surgery
Dr. Georgia Tomaras is a tenured Professor of Surgery, Professor of Immunology, Professor of Molecular Genetics and Microbiology and is a Fellow of the American Academy of Microbiology (AAM) and a Fellow of the American Association for the Advancement of Science (AAAS).  Dr. Tomaras is Co-Director of the Center for Human Systems Immunology (CHSI) Duke University and Director of the Duke Center for AIDS Research (CFAR). Her national and international leadership roles i
Vandergrift

Nathan A. Vandergrift

Associate Professor in Medicine
Walter

Emmanuel Benjamin Walter Jr.

Professor of Pediatrics
Dr. Emmanuel Walter, MD, MPH, Professor of Pediatrics, serves as the Duke Human Vaccine Institute (DHVI) Chief Medical Officer and directs the Duke Vaccine and Trials Unit. In these roles, Dr. Walter provides strategic and operational leadership for clinical research conducted at the Institute.  In addition, he provides oversight of regulatory compliance for DHVI clinical research activities. Dr. Walter has dedicated his career to advancing research and clinical practice in vacci

John Franklin Whitesides

Assistant Professor in Medicine
Woods

Christopher Wildrick Woods

Professor of Medicine
1. Emerging Infections 2. Global Health 3. Epidemiology of infectious diseases 4. Clinical microbiology and diagnostics 5. Bioterrorism Preparedness 6. Surveillance for communicable diseases 7. Antimicrobial resistance

Jae-Sung Yu

Assistant Professor in Medicine
Jae-Sung Yu, PhD is Assistant Professor of Medicine at Duke University Medical Center. He received his PhD in Microbiology from the University of Connecticut in 1998. Yu is currently developing rM. smegmatis vectors for HIV-1 vaccines funded by a grant from the Bill and Melinda Gates grant awarded in July 2006. Yu is also working on a program project grant, “HIV, TB and Malaria Vaccine Development for Africa,” expressing HIV and malaria antigens in an attenuated mycobacterium
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
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Alphabetical list of authors with Scholars@Duke profiles.
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