Abstract

The major accomplishments for this year are summarized below. 1) Nipah virus (NiV) is an emerging zoonotic paramyxovirus related to HeV that causes severe and often fatal disease in pigs and humans. There are currently no vaccines or treatments approved for human use. A clinical trial phase I with 40 volunteers was initiated in Australia and is ongoing. 2) The recently discovered Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to infect humans with high mortality. Specific, highly effective therapeutics and vaccines against the MERS-CoV are urgently needed to safe human lives and address the pandemic concerns. We identified last year three human monoclonal antibodies (mAbs), m336, m337 and m338, targeting the receptor (CD26/DPP4) binding domain (RBD) of the MERS-CoV spike glycoprotein from a very large (size 10to11) naive human antibody library. The most potent antibody, m336, is being tested in animal models of MERS-CoV infections.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011156-07
Application #
9153799
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

van Doremalen, Neeltje; Falzarano, Darryl; Ying, Tianlei et al. (2017) Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets. Antiviral Res 143:30-37
Agrawal, Anurodh Shankar; Ying, Tianlei; Tao, Xinrong et al. (2016) Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection. Sci Rep 6:31629
Ying, Tianlei; Li, Wei; Dimitrov, Dimiter S (2016) Discovery of T-Cell Infection and Apoptosis by Middle East Respiratory Syndrome Coronavirus. J Infect Dis 213:877-9
Houser, Katherine V; Gretebeck, Lisa; Ying, Tianlei et al. (2016) Prophylaxis With a Middle East Respiratory Syndrome Coronavirus (MERS-CoV)-Specific Human Monoclonal Antibody Protects Rabbits From MERS-CoV Infection. J Infect Dis 213:1557-61
Dimitrov, Dimiter S; Jiang, Shibo; Ying, Tianlei et al. (2015) No evidence for a superior platform to develop therapeutic antibodies rapidly in response to MERS-CoV and other emerging viruses. Proc Natl Acad Sci U S A 112:E5115
Ying, Tianlei; Li, Haoyang; Lu, Lu et al. (2015) Development of human neutralizing monoclonal antibodies for prevention and therapy of MERS-CoV infections. Microbes Infect 17:142-8
Ying, Tianlei; Prabakaran, Ponraj; Du, Lanying et al. (2015) Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody. Nat Commun 6:8223
Geisbert, Thomas W; Mire, Chad E; Geisbert, Joan B et al. (2014) Therapeutic treatment of Nipah virus infection in nonhuman primates with a neutralizing human monoclonal antibody. Sci Transl Med 6:242ra82
Ying, Tianlei; Du, Lanying; Ju, Tina W et al. (2014) Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies. J Virol 88:7796-805
Zhu, Zhongyu; Prabakaran, Ponraj; Chen, Weizao et al. (2013) Human monoclonal antibodies as candidate therapeutics against emerging viruses and HIV-1. Virol Sin 28:71-80

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