Researchers at Albert Einstein College of Medicine in New York and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) have engineered the first antibodies that can potentially neutralise the two deadliest strains of the virus that causes Ebola hemorrhagic fever.
The findings, made in mice, are seen as a significant step toward immunotherapies that are effective against all strains of Ebola virus that cause human disease. Study co-leader Jonathan Lai, Ph.D., associate professor of biochemistry at Einstein, said: “A broadly effective immunotherapy for Ebola virus would be a tremendous advance, since it’s impossible to predict which strain of the virus will cause the next outbreak.” Zaire Ebola virus (EBOV) was responsible for the 2014 Ebola outbreak in West Africa, the largest in history. The next-most pathogenic strain of Ebola virus is Sudan Ebola virus (SUDV). Study co-leader John M. Dye, Ph.D., branch chief of viral immunology at USAMRIID, said: “This strain is also a concern because outbreaks are occurring more frequently, and it has been responsible for large outbreaks in the past.” Although a Zaire-specific vaccine is in clinical trials, no vaccine has yet been approved for preventing infection from any strain of Ebola virus and therapies for people who become infected are very limited.
ZMapp, a cocktail of three monoclonal antibodies, is the most promising of several experimental immunotherapies for Ebola virus now in development. However, say the study team, ZMapp’s antibodies are specific for EBOV and would not work against the other two Ebola strains that have caused major outbreaks. In addition to Zaire and Sudan, the third major strain is Bundibugyo. In previous work, Dr Jonathan Lai and his colleagues used a technique called synthetic antibody engineering to create the first humanized antibodies against SUDV. For the latest study, Dr Lai, Ph.D. student Julia Frei and postdoctoral fellow Elisabeth Nyakatura engineered “bispecific” antibodies that contain key glycoprotein-binding sequences from both the EBOV and SUDV antibodies. The antibodies effectively neutralised both EBOV and SUDV in tissue culture studies. In addition, the antibodies provided high levels of protection for mice that had been exposed to lethal doses of either of the viruses.
The antibodies must still be tested in larger animals and in humans to know whether they will be effective. Dr Lai said: “It might best be suited for preventing local outbreaks from getting out of hand, as happened in the recent West Africa Ebola virus epidemic. “It’s also possible that a therapy like this could be used prophylactically, to protect health workers or family members who come into contact with Ebola virus patients
