Exploiting the early immune response in Chikungunya fever promises to provide protection

July 4, 2012, Agency for Science, Technology and Research (A*STAR), Singapore
A*STAR researchers have shown that the antibody produced in the initial immune response to CHIKV recognizes the protein E2 and binds to a specific site called E2EP3, seen here in red. This site projects from the surface of the virus, making it easily accessible to the antibody. © 2012 EMBO Molecular Medicine

(Medical Xpress) -- Chikungunya fever is a viral disease that has re-emerged to cause epidemics in the Pacific region within the last decade. It is caused by the Chikungunya virus (CHIKV), which is transmitted by mosquitoes and causes symptoms including fever, rash and joint pain. It can be incapacitating, with some patients developing severe chronic symptoms, and it is sometimes fatal. The main current control measure is to prevent exposure to mosquitoes; a vaccine would reduce the threat of CHIKV.

Lisa Ng of the A*STAR Singapore Network and co-workers have now provided insight into the natural immune response that may help in developing a vaccine. Ng’s group showed previously that the initial to CHIKV is spearheaded by a specific class of antibody that disables the virus when bound to it. Their latest research reveals a way to exploit this clinically.

Working with clinicians at the Tan Tock Seng Hospital, Ng and her team took blood samples from CHIKV-infected patients and tested them to see if they contained any antibodies that recognize proteins from the surface of the virus. They found that at early stages of recovery, patients’ blood contained large amounts of an antibody that targets a protein known as E2, which projects from the surface of CHIKV (see image). The same antibody was found in different groups of patients, showing that it is a reliable indicator of early infection.

The team confirmed that this antibody neutralizes CHIKV by adding blood samples to virus which was then used to infect susceptible human cells. If the blood samples contained the antibody, infection rates were reduced, whereas removing the antibody from the samples beforehand left infection rates high.

Having identified that the antibody recognizes E2, the researchers then tested its ability to recognize fragments of the protein. This allowed identification of the epitope, or the exact site on the protein, that the antibody binds to, which they called E2EP3.

When they vaccinated mice with a protein fragment equivalent to this epitope, the mice produced the same antibody in response. On subsequent infection with CHIKV, the vaccinated mice also showed milder symptoms, making the epitope a promising basis for a future vaccine in humans.

“[This study is] highly relevant for the rational design of CHIKV vaccines and for the development of diagnostics for optimal clinical management of patients,” says Ng. “It may also inspire similar studies with other arthritic arboviruses that in many parts of the world cause severe morbidity with extensive incapacitation.”

Explore further: Breakthroughs in Chikugunya research spell new hope for better treatment and protection

More information: Kam, Y-W et al. Early neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein. EMBO Molecular Medicine 4, 1–14 (2012). dx.doi.org/10.1002/emmm.201200213

Related Stories

Breakthroughs in Chikugunya research spell new hope for better treatment and protection

March 14, 2012
Recent breakthroughs in Chikungunya research spearheaded by scientists at A*STAR's Singapore Immunology Network (SIgN) have made great strides in the battle against the infectious disease. Working in close collaborations ...

Human antibody for dengue virus isolated

June 22, 2012
(Phys.org) -- A group of scientists in Singapore and the UK have isolated a human antibody capable of effectively neutralizing the mosquito-borne dengue virus. Dengue fever is currently incurable and infects an estimated ...

Researchers determine how antibody recognizes key sugars on HIV surface

November 23, 2011
HIV is coated in sugars that usually hide the virus from the immune system. Newly published research reveals how one broadly neutralizing HIV antibody actually uses part of the sugary cloak to help bind to the virus. The ...

Possible clues found to why HIV vaccine showed modest protection

April 4, 2012
Insights into how the first vaccine ever reported to modestly prevent HIV infection in people might have worked were published online today in the New England Journal of Medicine. Scientists have found that among adults who ...

Recommended for you

Quintupling inhaler medication may not prevent asthma attacks in children

March 19, 2018
Children with mild to moderate asthma do not benefit from a common practice of increasing their inhaled steroids at the first signs of an asthma exacerbation, according to clinical trial results published in The New England ...

How allergens trigger asthma attacks

March 19, 2018
A team of Inserm and CNRS researchers from the Institute of Pharmacology and Structural Biology have identified a protein that acts like a sensor detecting allergens in the respiratory tract that are responsible for asthma ...

Single steroid-bronchodilator treatment for control and rescue improves persistent asthma

March 19, 2018
When it comes to treating teens and adults with persistent asthma, using a single corticosteroid and long-acting bronchodilator treatment for both daily asthma control and for rescue relief during sudden asthma attacks is ...

Obesity and health problems: New research on a safeguard mechanism

March 16, 2018
Obesity and its negative impacts on health - including metabolic syndrome, type-2 diabetes mellitus and cardiovascular complications - are a global pandemic (Taubes, 2009). The worldwide incidence of obesity has more than ...

Immune system 'double agent' could be new ally in cancer fight

March 16, 2018
St. Jude Children's Research Hospital scientists have discovered that an enzyme called TAK1 functions like a "double agent" in the innate immune response, serving as an unexpected regulator of inflammation and cell death. ...

Artificial sweetener Splenda could intensify symptoms in those with Crohn's disease

March 15, 2018
In a study that has implications for humans with inflammatory diseases, researchers from Case Western Reserve University School of Medicine and colleagues have found that, given over a six-week period, the artificial sweetener ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.