The use of monoclonal antibodies (mAbs) as therapeutics for filoviral infection has a long and well-vetted history in the filovirus community. Although some of the earliest studies indicated that antibodies may be ineffective in treating filoviral infection, the unprecedented 2013-2016 Ebola virus outbreak in Western Africa reinvigorated and accelerated the development of multiple therapeutic antibodies. For example, the Ebola virus single antibody treatment mAb114 and the tri-mAb cocktail REGN-EB3 showed significant protection during a recent clinical trial during the 2018-2020 Ebola virus outbreak in the Democratic Republic of the Congo. The success of these early antibody therapeutics opened up space that is ripe for discovery and development. There are now several new antibodies in the development pipeline with increased potency and breadth, extending the potential of antibodies to treat additional filoviruses known to cause major outbreaks, such as Bundibugyo virus, Sudan virus, and Marburg virus.
Both neutralizing and non-neutralizing antibodies are produced by filovirus survivors in response to infection. While neutralizing antibodies can block viral replication directly, non-neutralizing mechanisms of protection, such as engagement of the innate and adaptive immune response, are becoming increasingly appreciated as desirable phenotypic properties. However, the relative contribution of these two types of antibodies toward protection during natural infection is not well-understood, making it unclear how to translate in vivo success to humans. Determining the molecular basis of how such activities contribute to protection will drive the future of antibody development, potentially generating lessons that can be translated to other viruses.
This Research Topic will highlight some of the most recent advances in the realm of filoviral antibody immunotherapies. With this collection, we aim to capture the excitement of developments that have arisen most especially in the past decade, which saw both the 40th and 50th anniversaries of the discovery of marburgviruses and ebolaviruses. Further, we will provide insight into current developments of next-generation antibody therapeutics that are arising from close partnerships between industry, government and academia in order to advance candidates in a world that is seeing an ever-increasing threat of viral outbreaks.
We welcome the submission of Original Research and Review articles, including, but not limited to, the following subtopics:
1. The immune response to filoviruses, including natural infection and vaccination.
2. Response to immunotherapeutic treatment of filoviral infection.
3. Development of animal models for the evaluation of antibody therapeutics in the treatment of filoviral infections.
4. Non-neutralizing mechanisms of antibodies that contribute to protection from filoviral infections.
5. Structure-function relationships of therapeutic antibodies used in the treatment of filoviral infection.
6. Antibody discovery and development for use in the treatment of filoviral infections.
7. Antibodies as diagnostic tools for detecting filoviral infection.
8. Clinical development of filovirus therapeutics.
Dr. Paul Parren is the managing director and head of Research and Development at LAVA Therapeutics. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
The use of monoclonal antibodies (mAbs) as therapeutics for filoviral infection has a long and well-vetted history in the filovirus community. Although some of the earliest studies indicated that antibodies may be ineffective in treating filoviral infection, the unprecedented 2013-2016 Ebola virus outbreak in Western Africa reinvigorated and accelerated the development of multiple therapeutic antibodies. For example, the Ebola virus single antibody treatment mAb114 and the tri-mAb cocktail REGN-EB3 showed significant protection during a recent clinical trial during the 2018-2020 Ebola virus outbreak in the Democratic Republic of the Congo. The success of these early antibody therapeutics opened up space that is ripe for discovery and development. There are now several new antibodies in the development pipeline with increased potency and breadth, extending the potential of antibodies to treat additional filoviruses known to cause major outbreaks, such as Bundibugyo virus, Sudan virus, and Marburg virus.
Both neutralizing and non-neutralizing antibodies are produced by filovirus survivors in response to infection. While neutralizing antibodies can block viral replication directly, non-neutralizing mechanisms of protection, such as engagement of the innate and adaptive immune response, are becoming increasingly appreciated as desirable phenotypic properties. However, the relative contribution of these two types of antibodies toward protection during natural infection is not well-understood, making it unclear how to translate in vivo success to humans. Determining the molecular basis of how such activities contribute to protection will drive the future of antibody development, potentially generating lessons that can be translated to other viruses.
This Research Topic will highlight some of the most recent advances in the realm of filoviral antibody immunotherapies. With this collection, we aim to capture the excitement of developments that have arisen most especially in the past decade, which saw both the 40th and 50th anniversaries of the discovery of marburgviruses and ebolaviruses. Further, we will provide insight into current developments of next-generation antibody therapeutics that are arising from close partnerships between industry, government and academia in order to advance candidates in a world that is seeing an ever-increasing threat of viral outbreaks.
We welcome the submission of Original Research and Review articles, including, but not limited to, the following subtopics:
1. The immune response to filoviruses, including natural infection and vaccination.
2. Response to immunotherapeutic treatment of filoviral infection.
3. Development of animal models for the evaluation of antibody therapeutics in the treatment of filoviral infections.
4. Non-neutralizing mechanisms of antibodies that contribute to protection from filoviral infections.
5. Structure-function relationships of therapeutic antibodies used in the treatment of filoviral infection.
6. Antibody discovery and development for use in the treatment of filoviral infections.
7. Antibodies as diagnostic tools for detecting filoviral infection.
8. Clinical development of filovirus therapeutics.
Dr. Paul Parren is the managing director and head of Research and Development at LAVA Therapeutics. The other Topic Editors declare no competing interests with regard to the Research Topic subject.