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

Genomics reveals key macrophages' involvement in systemic sclerosis

January 18, 2018
A new international study has made an important discovery about the key role of macrophages, a type of immune cell, in systemic sclerosis (SSc), a chronic autoimmune disease which currently has no cure.

First vaccine developed against grass pollen allergy

January 18, 2018
Around 400 million people worldwide suffer in some form or other from a grass pollen allergy (rhinitis), with the usual symptoms of runny nose, cough and severe breathing problems. In collaboration with the Viennese firm ...

Researchers discover key driver of atopic dermatitis

January 17, 2018
Severe eczema, also known as atopic dermatitis, is a chronic inflammatory skin condition that is driven by an allergic reaction. In their latest study, researchers at La Jolla Institute reveal an important player that promotes ...

Who might benefit from immunotherapy? New study suggests possible marker

January 16, 2018
While immunotherapy has made a big impact on cancer treatment, the fact remains that only about a quarter of patients respond to these treatments.

Researchers identify new way to unmask melanoma cells to the immune system

January 16, 2018
system, which enables these deadly skin cancers to grow and spread.

How the immune system's key organ regenerates itself

January 15, 2018
With advances in cancer immunotherapy splashing across headlines, the immune system's powerful cancer assassins—T cells—have become dinner-table conversation. But hiding in plain sight behind that "T" is the organ from ...

0 comments

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.