A role for immune complexes in enhanced respiratory syncytial virus disease.
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.
Polack
Fernando P
FP
Department of Pediatrics, School of Medicine, Bloomberg School of Public Health at Johns Hopkins University, Baltimore, MD 21205, USA. fpolack@jhsph.edu
Teng
Michael N
MN
Collins
Peter L
PL
Prince
Gregory A
GA
Exner
Marcus
M
Regele
Heinz
H
Lirman
Dario D
DD
Rabold
Richard
R
Hoffman
Scott J
SJ
Karp
Christopher L
CL
Kleeberger
Steven R
SR
Wills-Karp
Marsha
M
Karron
Ruth A
RA
D000818:Animals; D000914:Antibodies, Viral / Q000502:physiology; D000936:Antigen-Antibody Complex / Q000502:physiology*; D016535:Bronchial Hyperreactivity / Q000150:complications; D003167:Complement Activation; D003176:Complement C3 / Q000502:physiology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018357:Respiratory Syncytial Virus Infections / Q000209:etiology* / Q000276:immunology; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology; D014764:Viral Proteins / Q000502:physiology
D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D003176:Complement C3; D022261:Respiratory Syncytial Virus Vaccines; D015164:Vaccines, Inactivated; D014764:Viral Proteins