A Role for Immune Complexes in Enhanced Respiratory Syncytial Virus Disease
By F. Polack, M. Teng, Peter L.Collins, G. Prince, M. Exner, H. Regele, Dario D. Lirman, R. Rabold, S. Hoffman, C. Karp and 3 more. 2002
406 citations recorded by the source corpus.
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.
Subfields: Epidemiology, Pulmonary and Respiratory Medicine
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Citations in the corpus
- Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, neutral): “This metric has been identified as a potentially important indicator of vaccine safety, as high levels of binding yet nonneutralizing or weakly neutralizing Abs may contribute to vaccine-associated enhancement of respiratory disease (Graham, 2020; Kim et al., 1969; Polack et al., 2002).”
- Inhibition of respiratory viruses by nasally administered siRNA (2005, unknown): “: use of denatured RSV proteins as vaccines leads to 'immunopotentiation' or vaccine-enhanced diseas”
- Respiratory Syncytial Virus: Virology, Reverse Genetics, and Pathogenesis of Disease (2013, background): “In addition, there was immunohistochemical evidence of immune complex deposition in small airways (Polack et al. 2002).”
- Influence of Respiratory Syncytial Virus F Glycoprotein Conformation on Induction of Protective Immune Responses (2016, background): “small airways and, hence, to enhanced pathology (4, 5).”
- Respiratory Syncytial Virus Fusion Glycoprotein Expressed in Insect Cells Form Protein Nanoparticles That Induce Protective Immunity in Cotton Rats (2012, background): “[31] have shown that antiFI RSV antibody responses exhibit a lack of antibody maturation due to poor toll-like receptor stimulation and suggest that low antibody avidity contribute to disease severity through the deposition of immune complexes identified in affected tissues [32].”