H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination.
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 articleSubject
HumansHemagglutinin 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/10161/22006Published Version (Please cite this version)
10.1371/journal.pone.0025797Publication 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.
Collections
More Info
Show full item recordScholars@Duke
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
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
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.
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
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,
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.
Micah Thomas McClain
Associate Professor of Medicine
Ryan Meyerhoff
House Staff
Program Start Year: 2013Barton Haynes Laboratory"Studies of Immunogens to Induce
Broadly Neutralizing HIV Antibodies"
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.
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
Nathan A. Vandergrift
Associate Professor in Medicine
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
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.
Alphabetical list of authors with Scholars@Duke profiles.

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info
Related items
Showing items related by title, author, creator, and subject.
-
A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.
Woods, Christopher W; McClain, Micah T; Chen, Minhua; Zaas, Aimee K; Nicholson, Bradly P; Varkey, Jay; Veldman, Timothy; ... (18 authors) (PLoS One, 2013)There is great potential for host-based gene expression analysis to impact the early diagnosis of infectious diseases. In particular, the influenza pandemic of 2009 highlighted the challenges and limitations of traditional ... -
Gene Expression Profiles Link Respiratory Viral Infection, Platelet Response to Aspirin, and Acute Myocardial Infarction.
Rose, Jason J; Voora, Deepak; Cyr, Derek D; Lucas, Joseph E; Zaas, Aimee K; Woods, Christopher W; Newby, L Kristin; ... (9 authors) (PLoS One, 2015)BACKGROUND: Influenza infection is associated with myocardial infarction (MI), suggesting that respiratory viral infection may induce biologic pathways that contribute to MI. We tested the hypotheses that 1) a validated ... -
Phylodynamic inference and model assessment with approximate bayesian computation: influenza as a case study.
Ratmann, O; Donker, G; Meijer, A; Fraser, C; Koelle, K (PLoS Comput Biol, 2012)A key priority in infectious disease research is to understand the ecological and evolutionary drivers of viral diseases from data on disease incidence as well as viral genetic and antigenic variation. We propose using a ...