Human monoclonal antibodies against Hendra and Nipah viruses
Inventors
Dimitrov, Dimiter S. • Zhu, Zhongyu • Broder, Christopher C.
Assignees
Henry M Jackson Foundation for Advancedment of Military Medicine Inc • US Department of Health and Human Services
Publication Number
US-8858938-B2
Publication Date
2014-10-14
Expiration Date
2025-11-04
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Abstract
The present invention relates to monoclonal antibodies that bind or neutralize Hendra or Nipah virus. The invention provides such antibodies, fragments of such antibodies retaining Hendra or Nipah virus-binding ability, fully human antibodies retaining Hendra or Nipah virus-binding ability, and pharmaceutical compositions including such antibodies. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. Additionally, the invention provides for prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention.
Core Innovation
The invention relates to monoclonal antibodies that bind or neutralize Hendra or Nipah virus. It provides such antibodies, fragments of such antibodies retaining virus-binding ability, fully human antibodies with these properties, and pharmaceutical compositions including such antibodies. Additionally, it covers isolated nucleic acids encoding these antibodies and host cells transformed with such nucleic acids. The invention further provides prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids described.
Nipah virus (NiV) and Hendra virus (HeV) are emerging paramyxoviruses comprising the Henipavirus genus, distinct for their broad species tropisms and ability to cause fatal disease in animals and humans. They are BSL-4 pathogens with aerosol transmission potential causing severe respiratory illness and febrile encephalitis. Currently, no therapeutics or vaccines are available for these viruses. Although antibody responses occur during infection, human monoclonal antibodies (hmAbs) have not been identified prior to this invention. Neutralizing antibodies are important for protection from viral infections, so developing neutralizing hmAbs against NiV and HeV could have significant implications for prophylaxis, immunotherapy, vaccine design, diagnosis, and research.
This invention reports the identification of potent neutralizing human monoclonal antibodies targeting the viral envelope glycoprotein G of HeV and NiV. These were identified using a highly purified, oligomeric, soluble HeV G glycoprotein as antigen to screen a large naïve human phage-display library. Among the antibodies, one showed exceptional potency against infectious HeV, and another neutralized both HeV and NiV. As these are fully human antibodies, they are suitable bases for prophylaxis and treatment of humans infected with these viruses.
Claims Coverage
The patent describes two main inventive features covered by the independent claims concerning a specific antibody and a pharmaceutical composition including this antibody.
Antibody comprising the full-length sequence of deposited cells
An antibody comprising the full-length antibody sequence produced by the cells deposited as American Type Culture Collection (ATCC) Deposit Number PTA-13287.
Pharmaceutical composition including the claimed antibody
A pharmaceutical composition comprising the antibody defined above and a pharmaceutically acceptable carrier.
The claims cover a full-length antibody with the specific sequence from the deposited cell line and pharmaceutical compositions containing this antibody with suitable carriers.
Stated Advantages
Provides fully human monoclonal antibodies that potently neutralize Hendra and Nipah viruses, the first such human monoclonal antibodies identified.
Exhibits exceptional potency in neutralizing infectious Hendra virus, with high efficacy at low antibody concentration.
The antibodies inhibit viral entry by competing with the receptor ephrin-B2, thus blocking viral binding and fusion.
Fab fragments can be produced efficiently in bacteria, facilitating inexpensive production.
Fully human antibodies reduce the likelihood of immune responses against the antibody itself, suitable for therapeutic use.
Antibodies serve multiple roles including prophylaxis, therapy, diagnosis, research reagents, and as bases for vaccine and drug development.
Documented Applications
Prophylaxis of Hendra Virus Disease or Nipah Virus Disease in humans and animals.
Therapeutic treatment of active Hendra or Nipah virus infection in humans and other animals.
Pharmaceutical compositions including the antibodies for immunoprophylaxis and immunotherapy.
Diagnostic methods employing the antibodies for in vitro detection of virus in biological samples and tissues, including immunoassays and immunohistochemical assays.
In vivo detection of Hendra or Nipah virus by administering detectably labeled antibodies for imaging.
Research reagents for studying the viruses and their envelope glycoproteins.
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