Stabilization of a Broadly Neutralizing Anti-Chikungunya Virus Single Domain Antibody

Frontiers in Medicine

Dan Zabetakis¹  Patricia M. Legler¹  Jinny L. Liu¹  George P. Anderson¹  Ellen R. Goldman¹  Emily M. Webb²  James Weger-Lucarelli²  Christina L. Gardner³  Pamela J. Glass³  Crystal W. Burke³ 

[1] U.S. Naval Research Laboratory, Center for BioMolecular Science and Engineering, Washington, DC, United States;Virginia Polytechnic Institute and State University, Blacksburg, VA, United States;Virology Division, U.S. Army Medical Research Institute for Infectious Diseases, Fort Detrick, MD, United States;

关键词: chikungunya virus;    old world;    new world;    alphavirus;    neutralization;    melting temperature;    single domain antibody;   

DOI  :  10.3389/fmed.2021.626028

来源: Frontiers

【 摘 要 】

A single domain antibody (clone CC3) previously found to neutralize a vaccine strain of the chikungunya virus (PRNT50 = 2. 5 ng/mL) was found to be broadly neutralizing. Clone CC3 is not only able to neutralize a wild-type (WT) strain of chikungunya virus (CHIKV), but also neutralizes WT strains of Mayaro virus (MAYV) and Ross River virus (RRV); both arthralgic, Old World alphaviruses. Interestingly, CC3 also demonstrated a degree of neutralizing activity against the New World alphavirus, Venezuelan equine encephalitis virus (VEEV); albeit both the vaccine strain, TC-83, and the parental, WT Trinidad donkey strain had PRNT50 values ~1,000-fold higher than that of CHIKV. However, no neutralization activity was observed with Western equine encephalitis virus (WEEV). Ten CC3 variants designed to possess a range of isoelectric points, both higher and lower, were constructed. This approach successfully identified several lower pI mutants which possessed improved thermal stabilities by as much as 10°C over the original CC3 (Tm = 62°C), and excellent refolding abilities while maintaining their capacity to bind and neutralize CHIKV.

【 授权许可】

CC BY