The Journal of Experimental Medicine
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Published online 9 September 2002 doi:10.1084/jem.20020781
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© Rockefeller University Press, 0022-1007/2002/9/859/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 6, September 16, 2002 859-865

Brief Definitive Report

A Role for Immune Complexes in Enhanced Respiratory Syncytial Virus Disease

Fernando P. Polack1,2,3, Michael N. Teng5, Peter L.Collins5, Gregory A. Prince6, Marcus Exner7, Heinz Regele8, Dario D. Lirman1,3, Richard Rabold4, Scott J. Hoffman1,3, Christopher L. Karp10, Steven R. Kleeberger9, Marsha Wills-Karp11 and Ruth A. Karron1,2

1 Department of Pediatrics, School of Medicine
2 Department of International Health, Bloomberg School of Public Health at Johns Hopkins University, Baltimore, MD 21205
3 Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health at Johns Hopkins University, Baltimore, MD 21205
4 Department of Environmental Health, Bloomberg School of Public Health at Johns Hopkins University, Baltimore, MD 21205
5 National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
6 Virion Systems Inc., Rockville, MD 20850
7 Department of Laboratory Medicine, University of Vienna, Vienna A-1090, Austria
8 Department of Clinical Pathology, University of Vienna, Vienna A-1090, Austria
9 National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle, NC 27709
10 Division of Molecular Immunology, Children's Hospital Research Foundation, Cincinnati, OH 45229
11 Division of Immunobiology, Children's Hospital Research Foundation, Cincinnati, OH 45229

Address correspondence to Fernando P. Polack, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., W5102, Baltimore, MD 21205. Phone: 410-955-1622; Fax: 410-955- 2791; E-mail: fpolack{at}jhsph.edu

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and viral pneumonia in infants and young children. Administration of a formalin inactivated vaccine against RSV to children in the 1960s resulted in increased morbidity and mortality in vaccine recipients who subsequently contracted RSV. This incident precluded development of subunit RSV vaccines for infants for over 30 years, because the mechanism of illness was never clarified. An RSV vaccine for infants is still not available.

Here, we demonstrate that enhanced RSV disease is mediated by immune complexes and abrogated in complement component C3 and B cell–deficient mice but not in controls. Further, we show correlation with the enhanced disease observed in children by providing evidence of complement activation in postmortem lung sections from children with enhanced RSV disease.

Key Words: respiratory syncytial virus • enhanced disease • immune complexes • airway hyperresponsiveness • compliment


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