Why the study?
VEEV is a mosquito-borne alphavirus causing lethal encephalitis in equines and lateral spread to humans, but has no approved human vaccine or therapeutic.
Bivalent single domain antibody constructs demonstrate highly effective in vitro neutralization of Venezuelan equine encephalitis virus, highlighting their potential as therapeutic agents.
Bivalent nanobody constructs enhance VEEV neutralization potency; leaves open in vivo efficacy and therapeutic translation.
Venezuelan equine encephalitis virus (VEEV) is a mosquito borne alphavirus which leads to high viremia in equines followed by lethal encephalitis and lateral spread to humans. In addition to naturally occurring outbreaks, VEEV is a potential biothreat agent with no approved human vaccine or therapeutic currently available. Single domain antibodies (sdAb), also known as nanobodies, have the potential to be effective therapeutic agents. Using an immune phage display library derived from a llama immunized with an equine vaccine that included inactivated VEEV, five sdAb sequence families were identified that showed varying ability to neutralize VEEV. One of the sequence families had been identified previously in selections against chikungunya virus, a related alphavirus of public health concern. A key advantage of sdAb is the ability to optimize properties such as neutralization capacity through protein engineering. Neutralization of VEEV was improved by two orders of magnitude by genetically linking sdAb. One of the bivalent constructs showed effective neutralization of both VEEV and chikungunya virus. Several of the bivalent constructs neutralized VEEV in cell-based assays with reductions in the number of plaques by 50% at protein concentrations of 1 ng/mL or lower, making future evaluation of their therapeutic potential compelling.
No takes yet. Share an insight, caveat, or question.
Liu et al. (2022) studied this question.