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Development of a Highly Protective Combination Monoclonal Antibody Therapy against Chikungunya Virus
Open accessAbstract
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes global epidemics of a debilitating polyarthritis in humans. As there is a pressing need for the development of therapeutic agents, we screened 230 new mouse anti-CHIKV monoclonal antibodies (MAbs) for their ability to inhibit infection of all three CHIKV genotypes. Four of 36 neutralizing MAbs (CHK-102, CHK-152, CHK-166, and CHK-263) provided complete protection against lethality as prophylaxis in highly susceptible immunocompromised mice lacking the type I IFN receptor (Ifnar(-/-) ) and mapped to distinct epitopes on the E1 and E2 structural proteins. CHK-152, the most protective MAb, was humanized, shown to block viral fusion, and require Fc effector function for optimal activity in vivo. In post-exposure therapeutic trials, administration of a single dose of a combination of two neutralizing MAbs (CHK-102+CHK-152 or CHK-166+CHK-152) limited the development of resistance and protected immunocompromised mice against disease when given 24 to 36 hours before CHIKV-induced death. Selected pairs of highly neutralizing MAbs may be a promising treatment option for CHIKV in humans.
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Metadata
- Authors
- Pal, P., Dowd, K. A., Brien, J. D., Edeling, M. A., Gorlatov, S., Johnson, S., Lee, I., Akahata, W., Nabel, G. J., Richter, M. K. S., Smit, J. M., Fremont, D. H., Pierson, T. C., Heise, M. T., & Diamond, M. S.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-04-18
- Volume
- 9
- Issue
- 4
- Pages
- e1003312
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- OpenAlex
- W2141231462
- Cited by
- 300
- References
- 0
- FWCI
- 26.16
- Type
- journal article
- Language
- en
- Open access
- gold
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- Pal, P., Dowd, K. A., Brien, J. D., Edeling, M. A., Gorlatov, S., Johnson, S., Lee, I., Akahata, W., Nabel, G. J., Richter, M. K. S., Smit, J. M., Fremont, D. H., Pierson, T. C., Heise, M. T., & Diamond, M. S. (2013). Development of a Highly Protective Combination Monoclonal Antibody Therapy against Chikungunya Virus. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.1003312
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