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Scientists Awarded $4.6 Million for Hepatitis C Vaccine Research

Scientists at The Scripps Research Institute (TSRI) have been awarded a five-year, $4.6 million grant from the National Institutes of Health (NIH) to study the human immune response to hepatitis C virus (HCV) infection and designs for an infection-preventing vaccine.

The grant will support the establishment of one of the NIH-funded Hepatitis C Cooperative Research Centers at TSRI to research the host immunological response to HCV infection. The Research Center will be led by TSRI Associate Professor Mansun Law, who will partner with TSRI Assistant Professor Jiang Zhu.

“We’ll focus on understanding the antibody response to HCV and using that information to design novel immunogens for an HCV vaccine,” said Law.

“The work will involve state-of-the-art computational tools for the HCV immunogen design and next-generation sequencing technology for analyzing immunogen-elicited B cell responses,” said Zhu.

HCV is an enormous public health problem. Estimates of the number of people currently infected range from 130 million to 200 million people around the world. The virus is transmitted by needle sharing among intravenous drug abusers, contaminated blood transfusions, the use of unsterilized medical tools, and other forms of blood-to-blood contact. It principally infects liver cells, although in the vast majority of cases, HCV infection remains virtually symptomless for decades until it eventually causes liver cancer, cirrhosis or other liver disease. New antiviral drugs can cure HCV infection in many cases but are extremely expensive and often are not used until infection has already caused serious liver damage. Antivirals also do not prevent re-infection.

“To eradicate this virus, we definitely need a vaccine, and so far we haven’t got one that’s been proven to work,” Law said.

In one arm of the project, Law and Zhu and their laboratories will study the details of how antibody-producing cells respond to HCV infection and how they can be stimulated to produce “broadly neutralizing” antibodies that bind to vulnerable spots on the virus and thereby prevent infection across a variety of strains. Experiments will include tests at the Southwest National Primate Research Center in Texas and “deep sequencing” of messenger RNA (mRNA) from human antibody-producing B cells to detail the pathways by which neutralizing antibodies originate.

Law and Zhu will use the immunological data to design new vaccine immunogens. The hope is that these, when inoculated into healthy people, will stimulate large quantities of broadly neutralizing antibodies against HCV, thereby providing strong protection against HCV infection.

Law has long been involved in HCV vaccine research, and in 2013, co-led a TSRI team that determined the first high-resolution atomic structure of HCV’s liver cell receptor binding site—a crucial vaccine target. Zhu, a former NIH scientist, is an expert on antibody responses to HIV infection and HIV vaccine design; he helped establish the Structural Bioinformatics Core Section at NIH’s Vaccine Research Center.

The NIH National Institute of Allergy And Infectious Diseases grant number is U19AI123861.

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Associate Professor Mansun Law (top) will partner with Assistant Professor Jiang Zhu to lead the new center at TSRI.