Recombinant antibodies targeting HIV-1 capsid protein (p24): the development of single-chain variable fragment

Abstract

Event Abstract Back to Event Recombinant antibodies targeting HIV-1 capsid protein (p24): the development of single-chain variable fragment Siti Aisyah Mualif1* and Mohammad Tasyriq Che Omar2 1 School of Biomedical Engineering & Health Sciences, Faculty of Engineering, University of Technology Malaysia, Malaysia 2 University of Science, Malaysia, Malaysia Background Human immunodeficiency virus (HIV) is the causative agent of acquired immune deficiency syndrome (AIDS) disease. The increasing morbidity and mortality due to HIV/AIDS in the past decades has sparked an interest to combat HIV/AIDS. However, ongoing research against the HIV/AIDS pandemic has failed to completely eradicate the infection. Introduction of highly active anti-retroviral therapy (HAART) in early 1990s has reduced the death rate of HIV/AIDS, but it has also resulted in the development of drug-resistant strains of HIV. Therefore, there is a pressing need to develop new and improved therapeutic modalities. HIV-1 capsid protein (p24) plays important roles in both early and late stages of HIV-1 replication. Small molecule inhibitors and peptides targeting p24 have shown to inhibit viral infection. However, rapid clearance and toxicity are major drawbacks associated with the aforementioned therapeutic modalities. The potential of monoclonal antibodies (mAbs) targeting p24 was discovered and found out that p24-targeting antibodies can be developed into novel therapeutic modalities. However, natural or hybridoma-derived mAbs are large molecules and difficult to engineer. Recombinant DNA technology allows the engineering of antibodies in multiple formats. Therefore, the aim of this study was to generate, characterize, and evaluate recombinant antibodies targeting HIV-1 p24. Methods Recombinant anti-p24 antibodies were generated from a combinatorial library of variable domains cloned from a hybridoma cell line and subsequently expressed on the surface of filamentous bacteriophage. Recombinant scFvs reacting specifically with HIV-1 p24 were isolated, expressed, and characterized. Results Out of 50 clones, three specific binders were identified via initial ELISA screening. Specificity of the binders was confirmed through competition studies and the selected clones were expressed in E. coli. The recombinant scFvs markedly inhibited p24 polymerization in vitro and HIV replication in Jurkat T cell lines when expressed as intracellular antibodies (intrabodies). Conclusion The anti-p24 scFvs engineered in this study have potential to be developed into novel antibody-based therapeutics against HIV. Acknowledgements This work was supported by a FRGS grant (203/CIPPT/67 11206) from the Ministry of Higher Education of Malaysia and Research Student Fund (USM/IPPT/2000/G-2/xiv) from AMDI, USM. Not forgetting the MOHE scholarship (KPT (BS) 841003015520) for the author to complete the work and a PAS grant (PY/2017/01374) from UTM, Johor Bahru to support the presentation. Keywords: HIV-1 p24, scFv, Phage display antibody library, anti-p24 scFv, therapeutic Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Poster Presentation Topic: Infectious diseases Citation: Mualif S and Che Omar M (2019). Recombinant antibodies targeting HIV-1 capsid protein (p24): the development of single-chain variable fragment. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00104 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 31 Oct 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. Siti Aisyah Mualif, School of Biomedical Engineering & Health Sciences, Faculty of Engineering, University of Technology Malaysia, Johor Bahru, Malaysia, aisyahmualif@utm.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Siti Aisyah Mualif Mohammad Tasyriq Che Omar Google Siti Aisyah Mualif Mohammad Tasyriq Che Omar Google Scholar Siti Aisyah Mualif Mohammad Tasyriq Che Omar PubMed Siti Aisyah Mualif Mohammad Tasyriq Che Omar Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.