La Jolla Institute for Allergy & Immunology awarded $18.8M NIH grant for infectious diseases study

February 17, 2016

Dr. Sette's team will provide key epitope information that the Queensland group can use in testing the blood samples. "We've looked at the malaria genome and have made bioinformatics predictions on which epitopes we think the immune system may recognize in malaria," said Dr. Sette. "Since the Queensland researchers are using blood samples from people previously infected, their immune systems' will have "memory" of the malaria parasite and will react to synthesized epitope pieces from it. It will become apparent, based on various body indicators, which epitopes triggered a defensive reaction from the immune system. We think this will provide some very exciting data that we hope may be useful in developing a first-ever malaria vaccine."

Institute researchers used the expansive resources of the Immune Epitope Database (IEDB), a major public health tool developed and hosted by the La Jolla Institute under a contract with the NIAID, to develop the malaria epitope predictions. The IEDB contains epitope data on a multitude of diseases, including malaria.

Regarding the dengue virus study, Dr. Sette said the Institute's research will be propelled by key advances in animal modeling made by researcher Sujan Shresta, Ph.D., who is co-investigator on the dengue study. In 2008, Dr. Shresta developed the world's first dengue virus mouse model showing key aspects of human infection. "For a long time, the central question in the field was, "Do the T cells protect or do they contribute to dengue virus disease?'" said Dr. Shresta, referring to the body's white blood cells that typically fight disease. Using mouse models, Dr. Shresta recently proved that T cells play a protective role. "Now we will explore whether they can also contribute to causing dengue disease symptoms," she said. The information will provide another important piece of the puzzle that Institute researchers say will move the world closer to a vaccine.

Now categorized by the U.S. Centers for Disease Control as an emerging disease threat, dengue virus infects an estimated 50 to 100 million people worldwide annually, with 250,000 cases of the severest form reported each year. Primarily found in Southeast Asia and Latin America, dengue cases have now been reported in Mexico and mosquitoes capable of transmitting the virus have been found recently in the U.S.

Regarding the smallpox component, Bjoern Peters, Ph.D., principal investigator on the study, said he will analyze the body's antibody response to the vaccinia virus, a close, but non-dangerous relative of the smallpox virus, which is the basis of the smallpox vaccine. "B cells make antibodies, which are the parts of the immune system that keep us from getting sick," he said. "The smallpox vaccine is the most successful vaccine ever developed," added Dr. Peters, noting that it led to the worldwide eradication of the disease. "By analyzing in detail which mechanisms make the smallpox vaccine work, we will develop better vaccines for other diseases in the future."

In addition, smallpox remains of research interest due to bioterrorism concerns that the virus could one day be reintroduced, said Dr. Peters. "Understanding the key aspects of viral protection against smallpox is important from this perspective as well."

Source: La Jolla Institute for Allergy and Immunology