Antibody landscapes after influenza virus infection or vaccination
Hills and valleys of influenza infection
Each one of us may encounter several different strains of the ever-changing influenza virus during a lifetime. Scientists can now summarize such histories of infection over a lifetime of exposure. Fonville et al. visualize the interplay between protective responses and the evasive influenza virus by a technique called antibody landscape modeling (see the Perspective by Lessler). Landscapes reveal how exposure to new strains of the virus boost immune responses and indicate possibilities for optimizing future vaccination programs.
Abstract
We introduce the antibody landscape, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.
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Published In
Science
Volume 346 | Issue 6212
21 November 2014
21 November 2014
Copyright
Copyright © 2014, American Association for the Advancement of Science.
Submission history
Received: 23 May 2014
Accepted: 3 October 2014
Published in print: 21 November 2014
Acknowledgments
We thank R. Bodewes, J. Bryant, D. Burke, N. Lewis, E. Selkov, B. Mühlemann, G. de Mutsert, and F. Pistoor. We also thank the staff of the Ha Nam Provincial Preventive Medicine Centre, the Hamlet health workers, and the National Institute for Hygiene and Epidemiology, Vietnam, for their support in conducting the fieldwork. We are indebted to the cooperation of the Ha Nam cohort and vaccine study participants. J.M.F. is supported by a Medical Research Council Fellowship (MR/K021885/1) and a Junior Research Fellowship from Homerton College, L.C.K. by the Gates-Cambridge Scholarship and the NIH Oxford-Cambridge Scholars program, and C.A.R. by a Royal Society University Research Fellowship (RG55423). We acknowledge the National Institute of Allergy and Infectious Diseases–NIH Centers of Excellence for Influenza Research and Surveillance contracts HHSN266200700010C and HHSN272201400008C, Nederlandse Organisatie voor Wetenschappelijk Onderzoek VICI grant 91896613, the European Union FP7 programs EMPERIE (223498) and ANTIGONE (278976), Human Frontier Science Program grant P0050/2008, the Wellcome Trust (WT087982MA), and NIH Director’s Pioneer Award DP1-OD000490-01. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian government Department of Health. A.D.M.E.O. (as Chief Scientific Officer of Viroclinics Biosciences BV) has advisory affiliations with GlaxoSmithKline, Novartis, and Roche. Sequences of the influenza viruses used in this study are available in GenBank with accession numbers: KM821278 to KM821358. Erasmus Medical Center (Rotterdam, the Netherlands) requires a materials transfer agreement for sharing viruses and antisera.
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