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


ABSTRACT: 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.

SUBMITTER: Liu JL 

PROVIDER: S-EPMC7876468 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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

Liu Jinny L JL   Webb Emily M EM   Zabetakis Dan D   Burke Crystal W CW   Gardner Christina L CL   Glass Pamela J PJ   Legler Patricia M PM   Weger-Lucarelli James J   Anderson George P GP   Goldman Ellen R ER  

Frontiers in medicine 20210128


A single domain antibody (clone CC3) previously found to neutralize a vaccine strain of the chikungunya virus (PRNT<sub>50</sub> = 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 alphavi  ...[more]

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