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A potential molecular mechanism for hypersensitivity caused by formalin-inactivated vaccines

Nature Medicine volume 12, pages 905–907 (2006)Cite this article

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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Figure 1: In vivo responses to formaldehyde treated vaccine antigens (Supplementary Methods online).
Figure 2: Effect of aldehyde treatment on vaccine-enhanced disease and immunogenicity (Supplementary Methods online).

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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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Author notes

  1. Amin Moghaddam and Wieslawa Olszewska: These authors contributed equally to this work.

Authors and Affiliations

  1. The Sir William Dunn School of Pathology, The University of Oxford, South Parks Road, Oxford, OX1 3RE, UK

    Amin Moghaddam & Quentin J Sattentau

  2. Department of Respiratory Medicine, Wright Fleming Institute, Imperial College London, Norfolk Place, W2 1PG, London, UK

    Wieslawa Olszewska, Belinda Wang, John S Tregoning, Rebecca Helson & Peter J M Openshaw

Authors
  1. Amin Moghaddam
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  2. Wieslawa Olszewska
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  3. Belinda Wang
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  4. John S Tregoning
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  5. Rebecca Helson
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  6. Quentin J Sattentau
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  7. Peter J M Openshaw
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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

Correspondence to Peter J M Openshaw.

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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)

Supplementary Methods (PDF 131 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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