A plant-biotechnology approach for producing highly potent anti-HIV antibodies for antiretroviral therapy consideration

Singh, Advaita APillay, PriyenKwezi, LusisizweTsekoa, Tsepo L2022-02-112022-02-112021-12Singh, A.A., Pillay, P., Kwezi, L. & Tsekoa, T.L. 2021. A plant-biotechnology approach for producing highly potent anti-HIV antibodies for antiretroviral therapy consideration. Journal of Genetic Engineering and Biotechnology, 19(1). http://hdl.handle.net/10204/122691687-157X2090-5920doi: 10.1186/s43141-021-00279-zhttp://hdl.handle.net/10204/12269Despite a reduction in global HIV prevalence the development of a pipeline of new therapeutics or pre-exposure prophylaxis to control the HIV/AIDS epidemic are of high priority. Antibody-based therapies offer several advantages and have been shown to prevent HIV-infection. Plant-based production is efficient for several biologics, including antibodies. We provide a short review on the work by Singh et al., 2020 who demonstrated the transient production of potent CAP256-VRC26 broadly neutralizing antibodies. These antibodies have engineered posttranslational modifications, namely N-glycosylation in the fragment crystallizable region and O-sulfation of tyrosine residues in the complementary-determining region H3 loop. The glycoengineered Nicotiana benthamiana mutant ( XTFT) was used, with glycosylating structures lacking ß1,2-xylose and/or a1,3-fucose residues, which is critical for enhanced effector activity. The CAP256-VRC26 antibody lineage targets the first and second variable region of the HIV-1 gp120 envelope glycoprotein. The high potency of this lineage is mediated by a protruding O-sulfated tyrosine in the CDR H3 loop. Nicotiana benthamiana lacks human tyrosyl protein sulfotransferase 1, the enzyme responsible for tyrosine O-sulfation. The transient coexpression of the CAP256-VRC26 antibodies with tyrosyl protein sulfotransferase 1 in planta had restored the efficacy of these antibodies through the incorporation of the O-sulfation modification. This approach demonstrates the strategic incorporation of posttranslational modifications in production systems, which may have not been previously considered. These plant-produced CAP256-VRC26 antibodies have therapeutic as well as topical and systemic pre-exposure prophylaxis potential in enabling the empowerment of young girls and women given that gender inequalities remain a major driver of the epidemic.FulltextenAnti-HIV antibodiesPlant-biotechnology approachesGenetic engineeringA plant-biotechnology approach for producing highly potent anti-HIV antibodies for antiretroviral therapy considerationArticleSingh, A. A., Pillay, P., Kwezi, L., & Tsekoa, T. L. (2021). A plant-biotechnology approach for producing highly potent anti-HIV antibodies for antiretroviral therapy consideration. Journal of Genetic Engineering and Biotechnology, 19(1), http://hdl.handle.net/10204/12269Singh, Advaita A, Priyen Pillay, Lusisizwe Kwezi, and Tsepo L Tsekoa "A plant-biotechnology approach for producing highly potent anti-HIV antibodies for antiretroviral therapy consideration." Journal of Genetic Engineering and Biotechnology, 19(1) (2021) http://hdl.handle.net/10204/12269Singh AA, Pillay P, Kwezi L, Tsekoa TL. A plant-biotechnology approach for producing highly potent anti-HIV antibodies for antiretroviral therapy consideration. Journal of Genetic Engineering and Biotechnology, 19(1). 2021; http://hdl.handle.net/10204/12269.TY - Article AU - Singh, Advaita A AU - Pillay, Priyen AU - Kwezi, Lusisizwe AU - Tsekoa, Tsepo L AB - Despite a reduction in global HIV prevalence the development of a pipeline of new therapeutics or pre-exposure prophylaxis to control the HIV/AIDS epidemic are of high priority. Antibody-based therapies offer several advantages and have been shown to prevent HIV-infection. Plant-based production is efficient for several biologics, including antibodies. We provide a short review on the work by Singh et al., 2020 who demonstrated the transient production of potent CAP256-VRC26 broadly neutralizing antibodies. These antibodies have engineered posttranslational modifications, namely N-glycosylation in the fragment crystallizable region and O-sulfation of tyrosine residues in the complementary-determining region H3 loop. The glycoengineered Nicotiana benthamiana mutant ( XTFT) was used, with glycosylating structures lacking ß1,2-xylose and/or a1,3-fucose residues, which is critical for enhanced effector activity. The CAP256-VRC26 antibody lineage targets the first and second variable region of the HIV-1 gp120 envelope glycoprotein. The high potency of this lineage is mediated by a protruding O-sulfated tyrosine in the CDR H3 loop. Nicotiana benthamiana lacks human tyrosyl protein sulfotransferase 1, the enzyme responsible for tyrosine O-sulfation. The transient coexpression of the CAP256-VRC26 antibodies with tyrosyl protein sulfotransferase 1 in planta had restored the efficacy of these antibodies through the incorporation of the O-sulfation modification. This approach demonstrates the strategic incorporation of posttranslational modifications in production systems, which may have not been previously considered. These plant-produced CAP256-VRC26 antibodies have therapeutic as well as topical and systemic pre-exposure prophylaxis potential in enabling the empowerment of young girls and women given that gender inequalities remain a major driver of the epidemic. DA - 2021-12 DB - ResearchSpace DP - CSIR J1 - Journal of Genetic Engineering and Biotechnology, 19(1) KW - Anti-HIV antibodies KW - Plant-biotechnology approaches KW - Genetic engineering LK - https://researchspace.csir.co.za PY - 2021 SM - 1687-157X SM - 2090-5920 T1 - A plant-biotechnology approach for producing highly potent anti-HIV antibodies for antiretroviral therapy consideration TI - A plant-biotechnology approach for producing highly potent anti-HIV antibodies for antiretroviral therapy consideration UR - http://hdl.handle.net/10204/12269 ER -25260