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New discovery shows why vaccines can cause adverse reactions

Imperial College London, UK
Anthony Stephenson

New research from scientists at Imperial College London explains why some vaccines can have unexpected side effects, a finding that could aid the development of safer and more effective vaccines in the future.

The study published this month in Nature Medicine, shows how formalin, used in the manufacture of over half of all vaccines, can alter the vaccine's effect on the immune system.

The Wellcome Trust and Medical Research Council funded research shows that formalin causes chemical damage to vaccine proteins and creates reactive chemical groups called carbonyls. The immune system reacts strongly when it spots this damage.

In many cases, deliberately adding carbonyls to a vaccine can improve the body's immune response, such as with hepatitis A vaccines. However, in others, the presence of carbonyls can mean that the immune system overreacts once infection occurs and attacks the body in a damaging way.

In the 1960s, carbonyls in experimental vaccines for a virus known as RSV, which causes wheezy colds in children, triggered a powerful immune response that caused severe side effects leading to hospitalisation and several deaths.

Professor Peter Openshaw , from Imperial College London, who led the research, said: "Although we have known for sometime that certain vaccines can prove ineffective or in extreme cases, cause a bad reaction, we have not really known the exact mechanism behind this until now. This study gives us a new level of understanding about how vaccines boost the immune system."

The studies suggest that avoiding formalin in the manufacture of vaccines may in some cases reduce the frequency of side effects. It also shows that it it is possible to reverse the effects of formalin by additional chemical treatment. The team have taken out a patent which will allow them to further study and develop the use of carbonyls for vaccine development.

A potential molecular mechanism for hypersensitivity caused by formalin-inactivated

Nature Medicine - 12, 905 - 907 (2006)

Published online: 23 July 2006; | doi:10.1038/nm1456

Authors: Amin Moghaddam, Wieslawa Olszewska,
Belinda Wang, John S. Tregoning, Rebecca Helson,
Quentin J. Sattentau & Peter J. M. Openshaw

Correspondence should be addressed to Peter J.
M. Openshaw: p.openshaw@imperial.ac.uk

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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