Abstract
Heat, oxidation and exposure to aldehydes create reactive carbonyl groups on proteins, targeting antigens to scavenger receptors. Formaldehyde is widely used in making vaccines, but has been associated with atypical enhanced disease during subsequent infection with paramyxoviruses. We show that carbonyl groups on formaldehyde-treated vaccine antigens boost T helper type 2 (TH2) responses and enhance respiratory syncytial virus (RSV) disease in mice, an effect partially reversible by chemical reduction of carbonyl groups.
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Acknowledgements
This work was supported by program grants from the Medical Research Council of Great Britain (MRC) G0000635 and the Wellcome Trust 071381/Z/03/Z and by EC contract No QLK2-CT-1999-01044 'Impressuvac'.
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Q.J.S. and A.M. initiated studies on the role of carbonyls in driving a TH2 bias in immune responses, P.J.M.O. suggested that formaldehyde might generate carbonyls and A.M. demonstrated this experimentally; Q.J.S. and P.J.M.O. share senior authorship. Work on OVA was performed by A.M. and W.O., and on RSV by W.O., J.S.T., B.W. and R.H. All authors edited the manuscript, which was written by P.J.M.O.
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Supplementary information
Supplementary Fig. 1
Chemical effects of aldehyde treatments on antigens. (PDF 52 kb)
Supplementary Fig. 2
Viral load in challenged mice. (PDF 60 kb)
Supplementary Fig. 3
Antibody response to ovalbumin treated with glycoaldehyde. (PDF 24 kb)
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Moghaddam, A., Olszewska, W., Wang, B. et al. A potential molecular mechanism for hypersensitivity caused by formalin-inactivated vaccines. Nat Med 12, 905–907 (2006). https://doi.org/10.1038/nm1456
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DOI: https://doi.org/10.1038/nm1456
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