Dengue vaccine makes dengue infection far worse not better

“If someone has never been exposed to dengue, the vaccine seems to act like a silent infection. The initial exposure to the virus from the vaccine primes the immune system, so when they are infected again, the symptoms are more likely to be severe.”

Public Release: 1-Sep-2016

Dengue vaccine may increase risk of severe disease if used in areas with low rates of infection

Imperial College London

These infections are also more likely to need hospitalisation, suggests the study, by scientists from Imperial College London, John Hopkins Bloomberg School of Public Health and the University of Florida.

The research, published in the journal Science, analysed all publicly available clinical trial data for the vaccine. The results suggest that in people who have never been exposed to dengue before, the vaccine primes the immune system so that if they are subsequently infected, the infection is more severe.

However in people who are have been exposed to the virus before vaccination, the vaccine reduces the severity of future infections.

The researchers recommend testing people before they receive the vaccine, to establish if they have previously been exposed to the dengue virus. This would help avoid triggering an increase in serious cases of the disease.

Dengue is a viral infection that causes just under 400 million cases per year. According to the latest estimates, around half of the world’s population are thought to be at risk. The virus is spread by mosquitoes, and causes fever, headache, muscle and joint pain. In some cases, it can lead to a life-threatening condition called haemorrhagic fever which is a leading cause of death and serious illness among children in some Asian and Latin American countries.

Unlike most infectious diseases, the second time a person is infected with dengue is usually far more serious than the first. This may be why the vaccine appears to amplify the illness in some individuals, particularly young children.

Normally, when a person is infected with a virus their immune system builds defences against it. This means when they are infected a second time, the virus is destroyed before triggering symptoms. However, with dengue, the virus primes the immune system to work against the body. So when a person is infected a second time, a component of the immune system – called antibodies – help the virus infect the cells, leading to a more severe infection.

This has serious implications for the vaccine, explains Professor Neil Ferguson, co-lead author, who is the Director of the MRC Centre for Outbreak Analysis and Modelling at Imperial College London: “If someone has never been exposed to dengue, the vaccine seems to act like a silent infection. The initial exposure to the virus from the vaccine primes the immune system, so when they are infected again, the symptoms are more likely to be severe.”

The vaccine, produced by the company Sanofi-Pasteur, is available in six countries and has been trialled on around 30,000 people from ten countries.

After analysing the data, the research team formulated a computer model to predict the effectiveness of the vaccine if used more widely.

Professor Neil Ferguson said: “Having a licensed dengue vaccine available is a significant step forward for dengue control. However, we should be careful in considering where and how to use this vaccine as there is still uncertainty about the impact.”

The team stress the vaccine stills holds benefits – but only if used in areas heavily affected by dengue, where individuals being vaccinated are likely to have encountered the virus before.

Derek Cummings, Professor of Biology at the University of Florida and co-author of the study added: “In places with high transmission intensity, most people have been already exposed to dengue at the time of vaccination, and the vaccine has higher efficacy on average. However, in places with lower transmission intensity, were individuals haven’t been previously exposed, the vaccine can place people at risk of severe disease and overall, increase the number of hospitalized cases.”

Dr Isabel Rodriguez-Barraquer, joint first author of the research from Johns Hopkins Bloomberg School of Public Health, explained: “Our results indicate that screening potential vaccine recipients could maximize the benefits and minimise the risk of negative outcomes.”

The World Health Organization recommends that countries consider introduction of the dengue vaccine only in geographic settings (national or subnational) where data suggests a high burden of disease.

Professor Ferguson added: “Our model refines estimates of which places would see a decline in dengue incidence with large scale vaccination programmes, and which places should not implement programmes at this point in time. These results present the first published, independent predictions of the potential impact of vaccination that take account of recent data showing that the vaccine can increase the risk of severe dengue disease in young children.”

The authors hope their analysis can help inform policy-makers in evaluating this and other candidate dengue vaccines.

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The work was funded by the UK Medical Research Council, the NIHR UK National Institute of Health Research Health Protection Research Unit (HPRU) in Healthcare Associated Infections and Antimicrobial Resistance under the Health Protection Research Unit initiative, National Institute of Allergy and Infectious Diseases and National Institute of General Medical Sciences (NIH) under the MIDAS initiative, and the Bill and Melinda Gates Foundation.

Caroline Brogan
Research Media Officer (Research)
Imperial College London
caroline.brogan1@imperial.ac.uk
+44(0)20 7594 2412
Duty press officer mobile: +44 (0)7803 886 248

1. “Benefits and risks of the Sanofi-Pasteur dengue vaccine: Modeling optimal deployment” by Neil M. Ferguson et al is published in Science, 1 September 2016.

2. About Imperial College London

Imperial College London is one of the world’s leading universities. The College’s 16,000 students and 8,000 staff are expanding the frontiers of knowledge in science, medicine, engineering and business, and translating their discoveries into benefits for society.

Founded in 1907, Imperial builds on a distinguished past – having pioneered penicillin, holography and fibre optics – to shape the future. Imperial researchers work across disciplines to improve health and wellbeing, understand the natural world, engineer novel solutions and lead the data revolution. This blend of academic excellence and its real-world application feeds into Imperial’s exceptional learning environment, where students participate in research to push the limits of their degrees.

Imperial collaborates widely to achieve greater impact. It works with the NHS to improve healthcare in west London, is a leading partner in research and education within the European Union, and is the UK’s number one research collaborator with China.

Imperial has nine London campuses, including its White City Campus: a research and innovation centre that is in its initial stages of development in west London. At White City, researchers, businesses and higher education partners will co-locate to create value from ideas on a global scale. http://www.imperial.ac.uk

3. National Institute for Health Research

The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. The NIHR is the research arm of the NHS. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government’s strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website (http://www.nihr.ac.uk).

4. MRC

The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers’ money in some of the best medical research in the world across every area of health. Thirty-one MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. http://www.mrc.ac.uk

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Categories: . Vaccine failure

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