In the heart of Bangkok, a groundbreaking study led by Apidsada Chorpunkul, from the Department of Social and Environmental Medicine at Mahidol University, is paving the way for a new era in the fight against rabies. This deadly infectious disease, prevalent in tropical regions, has long posed a significant public health challenge. Chorpunkul’s research, published in the journal Heliyon, focuses on developing human monoclonal antibodies (MAbs) against the rabies virus (RABV) using a single-chain variable fragment (scFv) platform. This innovative approach could revolutionize postexposure prophylaxis (PEP) and potentially save countless lives.
The traditional methods of producing polyclonal antibodies for PEP have limitations, particularly in terms of production and quality control. Chorpunkul’s team aimed to address these issues by engineering therapeutic MAbs, which have proven effective against various infectious agents. “Our goal was to create a more reliable and efficient method for producing antibodies that can neutralize the rabies virus,” Chorpunkul explains. “By using the pMOD1 phage display system, we were able to construct immunized scFv libraries from human peripheral blood mononuclear cells, resulting in diverse VHVLκ and VHVLλ phage-displayed libraries.”
The research team successfully produced libraries with 2×107 and 5.4×106 clones, respectively. Through biopanning and ELISA, they identified scFvs with high affinity and binding specificity targeting the RABV glycoprotein. Six unique scFv clones were selected, each with diverse complementary determining region (CDR) sequences. Notably, HuRABVscFv1 and HuRABVscFv2 exhibited rapid fluorescent foci inhibition test (RFFIT)-neutralizing titers above the 0.5 IU/ml protective level, indicating their potential as effective neutralizing agents.
In silico molecular docking further revealed that the CDRs of these two neutralizing human clones interact mainly with antigenic sites III (HuRABVscFv1) and II (HuRABVscFv2) on the RABV glycoprotein. This detailed understanding of the interaction between the scFvs and the virus could lead to the development of more targeted and effective therapies.
The implications of this research are vast. If these scFvs can be successfully developed into MAbs, they could replace traditional PEP methods, offering a more standardized and controllable treatment option. This could be particularly impactful in regions like Thailand, where rabies remains a significant health threat. “Our findings suggest that these scFvs have the potential to be developed into monoclonal antibodies that could be used for postexposure prophylaxis,” Chorpunkul states. “This could greatly improve the quality and reliability of rabies treatment, ultimately saving more lives.”
The study, published in Heliyon (which translates to “Sun” in English), marks a significant step forward in the field of infectious disease research. As the world continues to grapple with emerging infectious diseases, the development of effective and reliable treatments is more critical than ever. Chorpunkul’s research not only advances our understanding of rabies but also sets a precedent for future developments in the field of monoclonal antibody therapies. The potential commercial impacts are substantial, as the energy sector and other industries could benefit from more effective and efficient treatments for infectious diseases, leading to a healthier and more productive workforce.