Plant-Based COVID-19 Vaccines: Current Status, Design, and Development Strategies of Candidate Vaccines

The prevalence of the coronavirus disease 2019 (COVID-19) pandemic in its second year has led to massive global human and economic losses. The high transmission rate and the emergence of diverse SARS-CoV-2 variants demand rapid and effective approaches to preventing the spread, diagnosing on time, and treating affected people. Several COVID-19 vaccines are being developed using different production systems, including plants, which promises the production of cheap, safe, stable, and effective vaccines. The potential of a plant-based system for rapid production at a commercial scale and for a quick response to an infectious disease outbreak has been demonstrated by the marketing of carrot-cell-produced taliglucerase alfa (Elelyso) for Gaucher disease and tobacco-produced monoclonal antibodies (ZMapp) for the 2014 Ebola outbreak. Currently, two plant-based COVID-19 vaccine candidates, coronavirus virus-like particle (CoVLP) and Kentucky Bioprocessing (KBP)-201, are in clinical trials, and many more are in the preclinical stage. Interim phase 2 clinical trial results have revealed the high safety and efficacy of the CoVLP vaccine, with 10 times more neutralizing antibody responses compared to those present in a convalescent patient’s plasma. The clinical trial of the CoVLP vaccine could be concluded by the end of 2021, and the vaccine could be available for public immunization thereafter. This review encapsulates the efforts made in plant-based COVID-19 vaccine development, the strategies and technologies implemented, and the progress accomplished in clinical trials and preclinical studies so far

BIN2/DWF12 Antagonistically Transduces Brassinosteroid and Auxin Signals in the Roots of Arabidopsis

Plant growth-stimulating hormones brassinosteroids (BRs) function via interactions with other hormones. However, the mechanism of these interactions remains to be elucidated. The unique phenotypes of brassinosteroid insensitive2/dwarf12-D (bin2/dwf12-D) mutants, such as twisted inflorescences and leaves, suggested that BIN2, a negative regulator of BR signaling, may be involved in auxin signaling. Furthermore, previously, we showed that auxin stimulates DWF4 expression. To determine the possible role of BIN2/DWF12 in Auxin signaling, we measured DWARF4pro:GUS activity through both GUS histochemical staining and in vivo GUS assay. We found that the GUS activity in the bin2/dwarf12-1D background dramatically increased relative to control. In addition, the number of lateral roots (LR) in bin2/dwf12-1D was greater than wild type, and the optimal concentration for auxin-mediated lateral root induction was lower in bin2/dwf12-1D; these findings suggest that BIN2 plays a positive role in auxin signaling. In contrast, ABA repressed both DWF4pro:GUS expression and lateral root development. However, the degree of repression was lower in bin2/dwf12-1D background, suggesting that BIN2 plays a role in ABA-mediated DWF4pro:GUS expression and subsequently in lateral root development, too. Therefore, it is likely that BIN2 plays a role of signal integrator for multiple hormones, such as BRs, auxin, and ABA.Perez-Perez JM, 2002, DEV BIOL, V242, P161, DOI 10.1006/dbio.2001.0543Li JM, 2001, PLANT PHYSIOL, V127, P14, DOI 10.1104/pp.127.1.14Steber CM, 2001, PLANT PHYSIOL, V125, P763, DOI 10.1104/pp.125.2.763Choe S, 2000, PLANT J, V21, P431, DOI 10.1046/j.1365-313x.2000.00693.xNoguchi T, 1999, PLANT PHYSIOL, V121, P743, DOI 10.1104/pp.121.3.743Piao HL, 1999, PLANT PHYSIOL, V119, P1527Choe S, 1999, PLANT PHYSIOL, V119, P897Choe SW, 1999, PLANT CELL, V11, P207Blazquez MA, 1998, PLANT CELL, V10, P791Claisse G, 2007, PLANT MOL BIOL, V64, P113, DOI 10.1007/s11103-007-9138-yGampala SS, 2007, DEV CELL, V13, P177, DOI 10.1016/j.devcel.2007.06.009Forde JE, 2007, CELL MOL LIFE SCI, V64, P1930, DOI 10.1007/s00018-007-7045-7Ryu H, 2007, PLANT CELL, V19, P2749, DOI 10.1105/tpc.107.053728Peng P, 2008, MOL PLANT, V1, P338, DOI 10.1093/mp/ssn001Gao YJ, 2008, PLANT CELL PHYSIOL, V49, P1013, DOI 10.1093/pcp/pcn078Vert G, 2008, P NATL ACAD SCI USA, V105, P9829, DOI 10.1073/pnas.0803996105Tang WQ, 2008, SCIENCE, V321, P557, DOI 10.1126/science.1156973Kim BK, 2008, BIOCHEM BIOPH RES CO, V374, P614, DOI 10.1016/j.bbrc.2008.07.073Jonak C, 2002, TRENDS PLANT SCI, V7, P457, DOI 10.1016/S1360-1385(02)02331-2Choe S, 2002, PLANT PHYSIOL, V130, P1506, DOI 10.1104/pp.010496NEMHAUSER JL, 2004, PLOS BIOL, V2, pE258, DOI DOI 10.1371/JOUNAL.PBIO.0020258CHOE S, 2004, PLANT HORMONES BIOSY, P156Jope RS, 2004, TRENDS BIOCHEM SCI, V29, P95, DOI 10.1016/j.tibs.2003.12.004Mora-Garcia S, 2004, GENE DEV, V18, P448, DOI 10.1101/gad.1174204Bao F, 2004, PLANT PHYSIOL, V134, P1624, DOI 10.1104/pp.103.036897Geisler M, 2004, MOL BIOL CELL, V15, P3393, DOI 10.1091/mbc.E03-11-0831Meijer L, 2004, TRENDS PHARMACOL SCI, V25, P471, DOI 10.1016/j.tips.2004.07.006Li JM, 2002, SCIENCE, V295, P1299Wang ZY, 2002, DEV CELL, V2, P505Nam KH, 2002, CELL, V110, P203, DOI 10.1016/S0092-8674(02)00814-0Li J, 2002, CELL, V110, P213, DOI 10.1016/S0092-8674(02)00812-7Kim GT, 2005, PLANT J, V41, P710, DOI 10.1111/j.1365-313X.2004.02330.xHe JX, 2005, SCIENCE, V307, P1634, DOI 10.1126/science.1107580Tanaka K, 2005, PLANT PHYSIOL, V138, P1117, DOI 10.1104/pp.104.059040Kim HB, 2006, PLANT PHYSIOL, V140, P548, DOI 10.1104/pp.105.067918Yoo MJ, 2006, BMC PLANT BIOL, V6, DOI 10.1186/1471-2229-6-3Vert G, 2006, NATURE, V441, P96, DOI 10.1038/nature04681Wang XL, 2006, SCIENCE, V313, P1118, DOI 10.1126/science.1127593Ohnishi T, 2006, PLANT CELL, V18, P3275, DOI 10.1105/tpc.106.045443Xue LW, 2009, Z NATURFORSCH C, V64, P225Zhang SS, 2009, P NATL ACAD SCI USA, V106, P4543, DOI 10.1073/pnas.0900349106Yan ZY, 2009, PLANT PHYSIOL, V150, P710, DOI 10.1104/pp.109.138099Ibanes M, 2009, P NATL ACAD SCI USA, V106, P13630, DOI 10.1073/pnas.0906416106Kim Y, 2009, J NEUROCHEM, V111, P344, DOI 10.1111/j.1471-4159.2009.06318.xKim TW, 2009, NAT CELL BIOL, V11, P1254, DOI 10.1038/ncb1970Stavang JA, 2009, PLANT J, V60, P589, DOI 10.1111/j.1365-313X.2009.03983.xKim WY, 2009, NAT NEUROSCI, V12, P1390, DOI 10.1038/nn.2408Choe SW, 1998, PLANT CELL, V10, P231Clouse SD, 1998, ANNU REV PLANT PHYS, V49, P427Li JM, 1997, CELL, V90, P929Clouse SD, 1996, PLANT PHYSIOL, V111, P671Li JM, 1996, SCIENCE, V272, P398Szekeres M, 1996, CELL, V85, P171JEFFERSON RA, 1987, EMBO J, V6, P3901

Plant-Expressed Receptor Binding Domain of the SARS-CoV-2 Spike Protein Elicits Humoral Immunity in Mice

The current 15-month coronavirus disease-19 (COVID-19) pandemic caused by SARS-CoV-2 has accounted for 3.77 million deaths and enormous worldwide social and economic losses. A high volume of vaccine production is urgently required to eliminate COVID-19. Inexpensive and robust production platforms will improve the distribution of vaccines to resource-limited countries. Plant species offer such platforms, particularly through the production of recombinant proteins to serve as immunogens. To achieve this goal, here we expressed the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein in the glycoengineered-tobacco plant Nicotiana benthamiana to provide a candidate subunit vaccine. This recombinant RBD elicited humoral immunity in mice via induction of highly neutralizing antibodies. These findings provide a strong foundation to further advance the development of plant-expressed RBD antigens for use as an effective, safe, and inexpensive SARS-CoV-2 vaccine. Moreover, our study further highlights the utility of plant species for vaccine development