Yellow Fever fragments may improve vaccine
virus may hold the key to a safer and more effective vaccine,
bringing hope to the 200,000 victims a year. Currently, no drug
treatment is effective against the virus.
In one of the first molecular studies of the human antibody response to yellow fever, scientists have discovered the key segment of the virus that people's immune systems need to spot and suppress this fatal re-emerging disease.
While the Ebola or Marburg hemorrhagic fever grabs more attention, yellow fever is the original viral hemorrhagic fever. The World Health Organisation estimates that the disease kills more than 30,000 people a year, mostly in Africa. Vaccination is the key strategy for people living in and travelling to tropical Africa, South America, and several Caribbean Islands, where yellow fever is endemic.
"The findings may help scientists improve the existing vaccine, which has rare but severe side effects," said Jan ter Meulen, associate professor of virology at Leiden University Medical Centre in The Netherlands.
The research team, from the Howard Hughes Medical Institute, identified an area on one of the viral proteins that stimulates an immune response. Antibodies produced by the immune system co-operate with this part of the protein, called the neutralising epitope, to combat infection.
"Current yellow fever vaccines must contain this fragment of instruction to the immune system," added ter Meulen.
In the last 20 years, however, yellow fever has been on the rise, mostly due to the lapse of immunisation programs in high-risk areas. More recently, serious and potentially fatal side effects from the vaccine have been reported, mainly in elderly persons in northern Europe.
"Yellow fever research was neglected because the vaccine was so effective," ter Meulen said.
Ter Meulen, who is also the lead author of the study, added: "Medical science works in cycles. Once the disease comes back, people realise they are lacking certain information."
In Yellow Fever, the mosquito-borne virus incubates for three to six days. Initial flu-like symptoms are followed by a brief remission of up to a day. Then, about 15 per cent of people suffer more dangerous complications- jaundice, liver, kidney, and heart damage, and bleeding from the mouth, nose, eyes or stomach.
At that stage, a person's own immune system, disrupted by its reaction to yellow fever virus infection, may lead to death rather than recovery.
Ter Meulen's study and its results echo the most recent study, in which Stephane Daffis, a graduate student at Philipps-Universitat in Marburg, Germany, took blood samples from two fully-recovered yellow fever patients and generated millions of specialised antibodies that made up their immune range.
The team then screened the libraries with a vaccine strain of yellow fever. Four of the antibodies neutralised yellow fever. Genetic analysis showed they had targeted part of the protein coating the virus. The epitope is called E-71, signifying its address on the envelope protein. Several other amino acids in another section of the folded protein contributed to the neutralisation.
"The results confirm and extend similar studies in mice, but the human antibody-virus binding configuration looks more complex," ter Meulen said.
In theory, the crucial antibodies, which have been cloned, could be used for prophylactic protection after suspected exposure, or for therapy, but ter Meulen does not think that pharmaceutical companies are likely to take this approach.
More likely, the findings could help manufacturers design a more consistent vaccine based on recombinant genetic technology, without the potential side effects from variations of the weakened virus strain.
Ter Meulen's, latest study is published in the July 5, 2005, issue of the journal Virology and published early online.
