Integrated BioTherapeutics and The Scripps Research Institute awarded $6.6 million to develop a vaccine that protects against all ebola viruses.
Ebola viruses (Ebolavirus, Sudan ebolavirus, Zaire ebolavirus (EBOV), Bundibugyo ebolavirus) and Marburg marburgvirus are filoviruses that cause hemorrhagic fever in humans, leading to death in 40-90% of those infected. In the recent West African EBOV outbreak, over 100,000 people died, while an additional 29,000 were infected and survived.. Infection by these viruses is mediated by different glycoproteins expressed on their surfaces – one per filovirus. These glycoproteins are the main targets for vaccines currently under development.
The ideal vaccine would be able to prevent infection by all ebola viruses, but there are structural differences between the surface glycoproteins of each virus. As a result, most current vaccine development programs only target EBOV and will not be effective against other filoviruses.
However, a new collaboration between Integrated BioTherapeutics (IBT) and The Scripps Research Institute (TSRI) was formed to address this issue and was awarded a $6.6 million, 5-year grant by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID) to develop a vaccine that protects against all ebola viruses.
The IBT/TSRI team has identified broadly neutralizing antibodies that may protect against every type of ebola viruses. IBT focuses on the discovery and development of vaccines and therapeutics for emerging bacterial and viral infectious diseases, including pan-filovirus immunotherapeutics and vaccines, and works closely with various US government agencies, including NIAID, the National Cancer Institute and others.
IBT is also in a partnership with Albert Einstein College of Medicine to develop biospecific antibodies targeting multiple broadly neutralizing epitopes on filovirus glycoproteins. The two organizations—through a Phase I small business technology transfer (STTR) grant from the NIAID—identified a lead candidate that provides protection against Ebolavirus and Sudan ebolavirus, thus neutralizing all ebola viruses. They were awarded Phase II of the program, which will investigate antibody manufacture in CHO cells and evaluation in nonhuman primates. IBT has also demonstrated that its antibody candidate CA45 can block cells from infection by EBOV, Sudan ebolavirus, and Bundibugyo ebolavirus in nonhuman primates.
The partnership between IBT and TSRI will involve the design of pan-Ebola virus vaccine candidates that can elicit broadly protective immune responses targeting structural sites that are shared between the different viral glycoproteins using the EBOV glycoprotein as a basis. The goal is to identify candidates for preclinical studies.
Other organizations participating in the research include the Albert Einstein College of Medicine, the US Army Medical Research Institute of Infectious Diseases (USAMIID), the Public Health Agency of Canada and the Sanford Burnham Prebys Medical Discovery Institute.
"This award will enable us to address a pressing global public health need, namely a single vaccine that can protect against all ebolaviruses,” stated IBT’s CSO, M. Javad Aman, Ph.D., a Co-principal Investigator for the collaboration. “To meet this challenge, we have assembled a unique team of experts in immunogen design, structural biology, vaccine development, and animal models of filovirus infection.”
Erica Ollmann Saphire, Ph.D., who is with TSRI, also as Co-principal Investigator, added: "A novel aspect of the program will be the use of state-of-the-art imaging and computational approaches. This design work will help us craft a vaccine to steer the immune response in the right directions."