Scientists find infection history must play key role in vaccine development

November 05, 2000

The timing and design of vaccines used to immunise against lung infections may have to change in the light of research findings by Imperial College scientists (1).

The research published today in the Journal of Experimental Medicine, shows for the first time that the previous infection history of an individual greatly affects the duration and severity of subsequent lung infections.

These findings stress the important yet ignored role that previous infection plays in the design of vaccines.

"Currently, most vaccines are tested on animals that have not previously been exposed to other lung infections. This is quite unrealistic when you are trying to vaccinate a human population which would have seen number of infections at various stages of their lives," says Dr Tracy Hussell of the Department of Biochemistry, Imperial College, the senior author on the paper.

Dr Tracy Hussell and her collaborators work on Respiratory Syncytial Virus (RSV). They show that mice which have been previously infected with influenza do not suffer the characteristic symptoms of RSV - weight loss, illness and lung eosinophilia - when they are subsequently infected with RSV. (See Notes to Editors 1 - 4).

"What we have found is that one viral infection in the lung profoundly changes the way we respond to an unrelated infection at the same site. By 'educating' itself, the immune system actually improves the way we respond to a second unrelated infection," said Dr Hussell.

In the 1960's children were vaccinated against RSV with an inactivated, dead form of the RSV virus (5).

Dr Gerhard Walzl, first author on the paper said: "When these children later encountered RSV virus in the community, the older children did not get as sick as vaccinated new-borns. Presumably, the older children would have encountered a number of infections in their lungs before they received the vaccine. This will have protected them from the harmful effects of the inactivated RSV vaccine. The younger children became quite ill and some died. The data may explain age related differences to vaccination."

"For instance, you would expect new-born babies to have experienced fewer infections than an adult and therefore you cannot expect these two different age groups to respond in exactly the same way to either a vaccine or an infection," he adds.

Dr Hussell continues: "There is no vaccine for RSV. In trying to prevent infection with one of the most important causes of infant hospitalisation in the Western world, our paper shows that the influence of our infection history and age on the way we respond to vaccines needs to be more fully addressed."
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For further information, please contact:

Taslima Khan
Press Office, Imperial College, London
Tel: 44-020-7594-6712
Fax: 44-020-7594-6700
Email: taslima.khan@ic.ac.uk
Mobile: 44-0-7803-88-62-48

1. Paper reference: Walzl G (a), Tafuro S (b), Moss P (c), Openshaw PJM (a) and Hussell T (a). Influenza virus lung infection protects from respiratory syncytial virus induced immunopathology. Journal of Experimental Medicine 2000, 192 (9).

(a) Centre for Molecular Microbiology and Infection, Department of Biochemistry, Imperial College of Science, Technology and Medicine, South Kensington, SW7 2AZ.

(b) Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DS.

(c) CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, B15 2TS.

2. The common cold that you catch during December, January and February is mostly caused by RSV, a viral infection localised in the upper airways and lungs. RSV is the most common cause of viral bronchiolitis, an inflammatory reaction in the lower airways, in infants and young children in the western world. It may lead to asthma and allergies in later life. A life threatening infection, RSV affects very young children because of their immature immune system, and since their lungs are not fully developed. Elderly people are affected too, because of their waning immunity. Other affected groups are people on immuno-suppressive therapy such as transplant patients and those undergoing chemo- and radio-therapy.

3. Influenza strain used in the research was X31.

4. Weight loss, illness and lung eosinophilia are symptomatic of RSV infection. Lung eosinophilia is caused by the recruitment of cells called eosinophils which contain toxic granules. These cells enter the lung during allergic responses and also after infections. Once in the lungs, the eosinophils de-granulate, causing a massive inflammatory and damaging response in the lung. The most severely affected children may require ventilation.

5. In the 1960's, children were vaccinated against RSV with an inactivated, dead form of the virus. The youngest children with the less mature immune system became very ill and some died. However, the older children who had a more experienced immune system were not so badly affected. The vaccine has since been tested in animal models and produced similar effects. The influence of infection history may explain the age related differences we see in the general population.

Ref: McIntosh, K. and J.M. Fishaut (1980). Immunopathologic mechanisms in lower respiratory tract disease of infants due to respiratory syncytial virus. Prog.Med.Virol. 26:94-118.

6. Imperial College of Science, Technology and Medicine is an independent constituent part of the University of London. Founded in 1907, the College teaches a full range of science, engineering, medical and management disciplines at the highest level. The College is the largest applied science and technology university institution in the UK, with one of the largest annual turnovers (UKP330 million in 1998-99) and research incomes (UKP122 million in 1998-99).

It is consistently rated in the top three UK university institutions for research quality, with an aggregate score of 6.09 out of 7 in the 1996 Research Assessment Exercise.

For further information see: www.ic.ac.uk

Imperial College London

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