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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1371/journal.pone.0025797

Publication Info

Moody, M Anthony, Ruijun Zhang, Emmanuel B Walter, Christopher W Woods, Geoffrey S Ginsburg, Micah T McClain, Thomas N Denny, Xi Chen, et al. (2011). H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination. PloS one, 6(10). p. 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.

Scholars@Duke

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 influenza, syphilis, HIV-1, and emerging infectious diseases.

Dr. Moody is the director of the Duke CIVICs Vaccine Center (DCVC) at (DHVI) and co-director of the Centers for Research of Emerging Infectious Disease Coordinating Center (CREID-CC). Dr. Moody is co-PI of a U19 program to develop a syphilis vaccine; this program is led by Dr. Justin Radolf at the University of Connecticut. Dr. Moody is also the director of the DHVI Accessioning Unit, a biorepository that provides support for work occurring at DHVI and with its many collaborators around the world by providing processing, shipping, and inventory support for a wide array of projects.

Dr. Moody and his team are involved in many networks studying vaccine response including the Collaborative Influenza Vaccine Innovation Centers (CIVICs) and the COVID-19 Prevention Network (CoVPN).

Walter

Emmanuel Benjamin Walter

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 vaccinology, infectious diseases, and child health. He currently serves as the principal investigator for the Duke Clinical Core of the Collaborative Influenza Vaccine Innovations Centers (CIVICs) funded by the National Institute of Allergy and Infectious Diseases (NIAID).  The goal of this work is to evaluate promising next generation influenza vaccine candidates in Phase I and Phase I/II clinical trials and human challenge studies.  He is also the Duke Principal Investigator for the CDC-funded Clinical Immunization Safety Assessment Project which conducts studies to identify risk factors and preventive strategies for adverse events following immunization, particularly in special populations. Lastly, he is the Principal Investigator for the  CDC-funded coordinating center of the influenza and other respiratory virus vaccine effectiveness network.  This work provides national estimates for influenza and other respiratory virus vaccine effectiveness in persons presenting with respiratory illness in the ambulatory setting.

Dr. Walter's focused area of interest include vaccine development, vaccine safety, vacc9je effectiveness, vaccine coverage, prevention and treatment of infectious diseases.

Woods

Christopher Wildrick Woods

Wolfgang Joklik Distinguished Professor of Global Health

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


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.