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RASP: rapid antibody functional screening by pentavalent phage display
Manpreet Kaur1, Abhishek Dubey1,2, Kartik Chandran1
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, USA.
Mabs
|February 9, 2026
Summary
Researchers developed Rapid Antibody functional Screening by Pentavalent phage display (RASP) to directly identify neutralizing heavy-chain antibody variable domains (VHHs) for antiviral therapies.
Area of Science:
- Biotechnology
- Immunology
- Virology
Background:
- Heavy-chain antibody variable domains (VHHs), also known as single-domain antibodies, are derived from camelids and are valuable tools for targeting pathogens.
- Conventional screening methods like phage display primarily rely on antibody-antigen binding, often necessitating further experiments to confirm neutralizing activity.
Purpose of the Study:
- To introduce and validate Rapid Antibody functional Screening by Pentavalent phage display (RASP), a high-throughput functional screening method for directly identifying neutralizing VHHs.
- To demonstrate the efficacy of RASP in discovering antiviral VHHs against various viruses.
Main Methods:
- Developed RASP by incorporating purified antibody-displaying phages for direct virus neutralization assays.
- Utilized hyperphage technology for pentavalent display, enhancing VHH phage neutralization potential.
- Screened a semi-synthetic VHH library against pseudotyped viruses (SARS-CoV-2, Junin virus, Ebola virus) using RASP.
Main Results:
- Demonstrated dose-dependent blockade of viral infection using VHH phages specific for SARS-CoV-2 and respiratory syncytial virus.
- Showcased the superiority of hyperphage-derived VHH phages over helper phage-derived VHH phages in neutralization assays.
- Successfully identified multiple neutralizing VHH candidates against SARS-CoV-2, Junin virus, and Ebola virus using RASP.
Conclusions:
- RASP is an innovative, high-throughput method for directly identifying neutralizing VHHs, accelerating antiviral antibody discovery.
- The pentavalent display feature of hyperphages significantly improves the efficiency of VHH-mediated viral neutralization assays.
- RASP offers broad applicability as a standalone or complementary platform for discovering potent antiviral VHHs.
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