New paper by the Lanzavecchia Lab on Protective human-derived antibody against Ebola successfully isolated and characterized
on Thursday, February 25, 2016
The Institute for Research in Biomedicine (IRB), affiliated to the Università della Svizzera italiana (USI), and Humabs BioMed SA, a Swiss antibody therapeutics company, have identified, isolated and characterized two Ebola virus neutralizing monoclonal antibodies from the blood of a survivor of an Ebola infection.
The results were achieved through an international collaboration with leading research institutes. As published in this week’s Science, one of the fully human antibodies is completely protective against lethal Ebola infection - even when given as single treatment and as late as five days after infection. A second publication, also in this week’s Science, identifies novel sites of vulnerability on the Ebola virus glycoprotein and reveals the molecular bases of virus neutralization by the human antibodies, providing new clues for vaccine design.
The Ebola virus causes hemorrhagic fever with a mortality rate of up to 90%. There is currently no approved Ebola therapy or vaccination. However, it is known that Ebola infection survivors carry life-long immunity preventing further infections. In a joint effort with researchers from the U.S. National Institute of Health (NIH) and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Humabs BioMed and IRB were able to isolate two human antibodies against Ebola from the blood of two survivors of a 1995 Ebola outbreak 11 years after infection. Two antibodies code-named mAb100 and mAb114 demonstrated high virus-neutralizing capacity even when mAb114 was given as a monotherapy five days after infection.
Subsequently, researchers from the U.S: National Institute for Allergic and Infectious Diseases (NIAID), the Geisel School of Medicine at Dartmouth (Hanover, USA) and the School of Medicine Tsinghua University (Beijing, China) in collaboration with Humabs and the IRB characterized the targets addressed by the two antibodies. Both interfere with a glycoprotein that is essential for the binding of the virus to its host cells. This protein contains a certain loop that is being removed before the virus can enter cells. While mAb100 prevents the removal of the loop, mAb114, which is effective as a monotherapy, remains attached to the protein even after the loop is cut out. This is an entirely novel site of Ebola virus vulnerability that has never been reported to date and may open up new possibilities for the development of further preventive and therapeutic measures.
The lead mAb114 antibody is now being manufactured and developed for clinical testing with the support of the Defense Advanced Research Projects Agency (DARPA, Arlington, USA).
“Our Institute is committed to the identification of potent and broadly neutralizing antibodies. This is important not only to deliver new therapeutics, but also to find the Achille’s heel of a pathogen in order to design more effective and safe vaccines,” said co-author Antonio Lanzavecchia, Director of the IRB, who has developed the Cellclone technology.
“These are major accomplishments in the search for a cure for Ebola,” said co-author Davide Corti, CSO of Humabs. “These data clearly demonstrate the efficiency of the Cellclone technology that delivered already several antibodies against infectious agents currently in clinical development. We believe in the therapeutic potential of mAb114 and we are very much looking forward to its clinical development.”
“Once again we have proven that Humabs is able to discover and develop anti-infective antibodies with high speed and remarkable results,” said Filippo Riva, CEO of Humabs. “This includes antibodies directed against emerging novel pathogens, such as MERS coronavirus and Zika virus. We will remain committed to developing cures against life-threatening diseases.”
The Institute for Research in Biomedicine (IRB) was founded in 2000 in Bellinzona and was affiliated to the Università della Svizzera italiana (USI) in 2010. Financed by private and public institutions, and by competitive grants, the IRB currently hosts 10 research groups and 105 researchers that investigate the mechanisms of host defence against infectious agents, cancer and degenerative diseases. With more than 460 publications in leading scientific journals, the IRB has gained an international reputation as a centre of excellence in human immunology.
About Humabs BioMed SA
Humabs BioMed, a spin-off of the Institute for Research in Biomedicine (IRB), is a leading Swiss antibody therapeutics company that discovers and develops superior antibodies directly derived from individuals who have successfully overcome major diseases. These "winner antibodies" have already passed natural selection by the immune system in response to disease and can easily be developed for standardized therapeutic use. The company currently focuses on infectious diseases, but also has selected antibodies against inflammatory diseases and cancer in the pipeline.
Humabs BioMed uses a unique technology platform developed at the IRB by Prof. Dr. Antonio Lanzavecchia, allowing the selection of monoclonal antibodies from immortalized human memory B cells, plasma cells or naïve B cells with unmatched, stable secretion rates. To date, the company has closed four major licensing deals with top pharmaceutical companies generating significant revenues. Two of these programs, partnered with MedImmune and Novartis, respectively, are currently in clinical development.
Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody. Davide Corti, John Misasi, Sabue Mulangu, Daphne A. Stanley, Masaru Kanekiyo, Suzanne Wollen, Aurélie Ploquin, Nicole A. Doria-Rose, Ryan P. Staupe, Michael Bailey, Wei Shi, Misook Choe, Hadar Marcus, Emily A. Thompson, Alberto Cagigi, Chiara Silacci, Blanca Fernandez-Rodriguez, Laurent Perez, Federica Sallusto, Fabrizia Vanzetta, Gloria Agatic, Elisabetta Cameroni, Neville Kisalu, Ingelise Gordon, Julie E. Ledgerwood, John R. Mascola, Barney S. Graham, Jean-Jacques Muyembe-Tamfun, John C. Trefry, Antonio Lanzavecchia, Nancy J. Sullivan
DOI: 10.1126/science.aad5224 (2016)
Structural and molecular basis for Ebola virus neutralization by protective human antibodies. John Misasi, Morgan S. A. Gilman, Masaru Kanekiyo, Miao Gui, Alberto Cagigi, Sabue Mulangu, Davide Corti, Julie E. Ledgerwood, Antonio Lanzavecchia, James Cunningham, Jean Jacques Muyembe-Tamfun, Ulrich Baxa, Barney S. Graham, Ye Xiang, Nancy J. Sullivan, Jason S. McLellan
DOI: 10.1126/science.aad6117 (2016)