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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cederna, J.B., Klinzman, D. & Stapleton, J.T. Vaccine 18, 892–898 (1999).
Openshaw, P.J.M., Culley, F.J. & Olszewska, W. Vaccine 20, s27–s31 (2001).
Murphy, B.R. & Walsh, E.E. J. Clin. Microbiol. 26, 1595–1597 (1988).
De Swart, R.L. et al. J. Virol. 76, 11561–11569 (2002).
Polack, F.P. et al. J. Exp. Med. 196, 859–865 (2002).
Hall, C.B. N. Engl. J. Med. 344, 1917–1928 (2001).
Flyvholm, M.A. Contact Dermatitis 53, 27–32 (2005).
Dean, R.T., Fu, S., Stocker, R. & Davies, M.J. Biochem. J. 324, 1–18 (1997).
Willis, M.S., Klassen, L.W., Tuma, D.J., Sorrell, M.F. & Thiele, G.M. Alcohol. Clin. Exp. Res. 26, 94–106 (2002).
Acharya, A.S. & Manning, J.M. Proc. Natl. Acad. Sci. USA 80, 3590–3594 (1983).
Galembeck, F., Ryan, D.S., Whitaker, J.R. & Feeney, R.E. J. Agric. Food Chem. 25, 238–245 (1977).
Nagai, K., Betsuyaku, T., Kondo, T., Nasuhara, Y. & Nishimura, M. Thorax 61, 496–502 (2006).
Horiuchi, S., Murakami, M., Takata, K. & Morino, Y. J. Biol. Chem. 261, 4962–4966 (1986).
Allison, M.E. & Fearon, D.T. Eur. J. Immunol. 30, 2881–2887 (2000).
Adams, S. et al. Front Biosci. 6, A17–A24 (2001).
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'.
Author information
Authors and Affiliations
Contributions
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.
Note: Supplementary information is available on the Nature Medicine website.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
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)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nm1456
This article is cited by
-
Profound structural conservation of chemically cross-linked HIV-1 envelope glycoprotein experimental vaccine antigens
npj Vaccines (2023)
-
Learning from the past: development of safe and effective COVID-19 vaccines
Nature Reviews Microbiology (2021)
-
Vaccination as a preventative measure contributing to immune fitness
npj Vaccines (2021)
-
Vaccine-Associated Enhanced Viral Disease: Implications for Viral Vaccine Development
BioDrugs (2021)
-
Dynamic Host Immune and Transcriptomic Responses to Respiratory Syncytial Virus Infection in a Vaccination-Challenge Mouse Model
Virologica Sinica (2021)