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.
Highlights
Chikungunya fever is a reemerging infectious disease caused by the chikungunya virus (CHIKV), a mosquito-borne alphavirus
We demonstrate that CC3 can neutralize other Old World as well as New World alphaviruses
We examined the ability of CC3 to neutralize two New World alphaviruses: Venezuelan equine encephalitis virus (VEEV) and Western equine encephalitis virus (WEEV)
Summary
Chikungunya fever is a reemerging infectious disease caused by the chikungunya virus (CHIKV), a mosquito-borne alphavirus. Old World alphaviruses typically result in persistent, or recurring, arthralgia after acute infection [1, 2], while the more virulent New World alphaviruses can cause lethal encephalitis [3]. In late 2013, CHIKV emerged in the Americas where it has caused millions of human infections [4]. Neutralizing antibodies have shown promise as both prophylactic and therapeutic agents against CHIKV [5]. To date, both polyvalent immunoglobulin (Ig) and monoclonal antibodies (mAbs) have been studied [6, 7]. Some mAbs have been reported to be broadly neutralizing, being effective against CHIKV and several other arthralgic Old World alphaviruses [8]
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