Single domain antibodies to Chikungunya virus
Inventors
Liu, Jinny Lin • Anderson, George P. • Goldman, Ellen R.
Assignees
Publication Number
US-11028152-B2
Publication Date
2021-06-08
Expiration Date
2039-07-17
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Abstract
Described herein are single-domain antibodies that might serve as alternatives to conventional monoclonal antibodies for either the detection or treatment of Chikungunya Virus (CHIKV).
Core Innovation
The invention relates to isolated single-domain antibodies (sdAbs) comprising protein sequences selected from SEQ ID Nos. 1-14 that can serve as alternatives to conventional monoclonal antibodies for detection or treatment of Chikungunya virus (CHIKV). These sdAbs have been isolated from llama-derived libraries immunized with CHIKV virus-like particles (VLPs) and show specificity and affinity for CHIKV envelope proteins, particularly the E1 protein.
The problem addressed by the invention is the need for effective detection and therapeutic tools against CHIKV, a mosquito-transmitted virus causing polyarthritis and currently threatening spread due to the mosquito vector Aedes albopictus. Existing antibody-based therapeutics using conventional IgGs face limitations such as exacerbation of illness through Fc-mediated processes and challenges in storage and stability, especially in resource-limited settings where cold chain maintenance is problematic. There is no currently available human vaccine or therapeutic for CHIKV, creating a need for stable, efficacious detection reagents and therapeutics.
The invention provides sdAbs that are robust and inherently thermally stable, can re-fold after denaturation, and can be engineered for enhanced utility. They are suitable for use in immunoassays for CHIKV detection and show potential for use as therapeutics to inhibit viral infection without the Fc-domain mediated adverse effects seen with conventional antibodies. The sdAbs like CC3 and CA6 demonstrate high affinity binding to CHIKV antigens and effective inhibition of viral infection in cellular assays, indicating their potential for both diagnostic and treatment applications.
Claims Coverage
The patent contains three main independent claims, covering isolated antibodies, methods of detection, and methods of inhibiting Chikungunya virus.
Isolated antibody comprising specific single-domain antibody sequences
An isolated antibody comprising a protein sequence selected from a group consisting of SEQ ID Nos. 1-14, which includes single-domain antibodies derived from llama immunizations against CHIKV.
Method of detecting Chikungunya virus using single-domain antibodies
A method of detecting CHIKV by contacting a sample suspected of containing the virus with a bound or immobilized antibody including a protein sequence from SEQ ID Nos. 1-14 under conditions permitting antigen binding, followed by rinsing to remove unbound reagents and producing a response indicative of CHIKV presence.
The independent claims cover isolated single-domain antibodies with specific sequences targeting CHIKV and their use in immunoassays for detection of the virus, providing novel sdAb agents and diagnostic methods.
Stated Advantages
Single-domain antibodies are rugged detection reagents with robust thermal stability and can refold after denaturation.
SdAbs can be engineered for enhanced stability and utility on various detection platforms, enabling use without refrigeration.
Their small size offers higher specific activity and faster tissue diffusion compared to conventional antibodies.
The lack of an Fc domain may reduce harmful Fc-mediated immune effects associated with CHIKV infection.
Documented Applications
Use of single-domain antibodies for detection of Chikungunya virus in immunoassays, including ELISA and MagPlex sandwich assays.
Use of single-domain antibodies as therapeutics to inhibit CHIKV infection in cell culture models, demonstrating viral inhibition and potential treatment.
Potential use of single-domain antibodies in point-of-care diagnostic tests suitable for resource-limited environments without cold chain requirements.
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