Title |
A “Trojan horse” bispecific-antibody strategy for broad protection against ebolaviruses
|
---|---|
Published in |
Science, September 2016
|
DOI | 10.1126/science.aag3267 |
Pubmed ID | |
Authors |
Anna Z Wec, Elisabeth K Nyakatura, Andrew S Herbert, Katie A Howell, Frederick W Holtsberg, Russell R Bakken, Eva Mittler, John R Christin, Sergey Shulenin, Rohit K Jangra, Sushma Bharrhan, Ana I Kuehne, Zachary A Bornholdt, Andrew I Flyak, Erica Ollmann Saphire, James E Crowe, M Javad Aman, John M Dye, Jonathan R Lai, Kartik Chandran |
Abstract |
There is an urgent need for monoclonal antibody (mAb) therapies that broadly protect against Ebola virus and other filoviruses. The conserved, essential interaction between the filovirus glycoprotein, GP, and its entry receptor Niemann-Pick C1 (NPC1) provides an attractive target for such mAbs, but is shielded by multiple mechanisms, including physical sequestration in late endosomes. Here, we describe a bispecific antibody strategy to target this interaction, in which mAbs specific for NPC1 or the GP receptor-binding site are coupled to a mAb against a conserved, surface-exposed GP epitope. Bispecific antibodies, but not parent mAbs, neutralized all known ebolaviruses by coopting viral particles themselves for endosomal delivery, and conferred post-exposure protection against multiple ebolaviruses in mice. Such 'Trojan horse' bispecific antibodies have potential as broad anti-filovirus immunotherapeutics. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 18 | 18% |
United Kingdom | 8 | 8% |
Switzerland | 2 | 2% |
Australia | 2 | 2% |
Germany | 2 | 2% |
India | 2 | 2% |
Singapore | 2 | 2% |
Canada | 2 | 2% |
Turkey | 1 | 1% |
Other | 16 | 16% |
Unknown | 43 | 44% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 69 | 70% |
Scientists | 22 | 22% |
Practitioners (doctors, other healthcare professionals) | 4 | 4% |
Science communicators (journalists, bloggers, editors) | 3 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
Unknown | 197 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 48 | 24% |
Student > Ph. D. Student | 41 | 21% |
Student > Bachelor | 24 | 12% |
Student > Master | 18 | 9% |
Professor | 10 | 5% |
Other | 23 | 12% |
Unknown | 34 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 54 | 27% |
Agricultural and Biological Sciences | 39 | 20% |
Immunology and Microbiology | 26 | 13% |
Medicine and Dentistry | 11 | 6% |
Chemistry | 10 | 5% |
Other | 18 | 9% |
Unknown | 40 | 20% |