SARS‑CoV-2 RBD219-N1C1: A yeast-expressed SARS-CoV-2 recombinant receptor-binding domain candidate vaccine stimulates virus neutralizing antibodies and T-cell immunity in mice

References

• WHO. The COVID-19 candidate vaccine landscape. 2020. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines
   Google Scholar
• Heaton PM. The Covid-19 vaccine-development multiverse. N Engl J Med. 2020;383:1986–88. doi:10.1056/NEJMe2025111.
   PubMed Web of Science ®Google Scholar
• Chen WH, Strych U, Hotez PJ, Bottazzi ME. The SARS-CoV-2 vaccine pipeline: an overview. Curr Trop Med Rep. 2020:1–4. doi:10.1007/s40475-020-00201-6.
   PubMedGoogle Scholar
• Slaoui M, Hepburn M. Developing safe and effective covid vaccines - operation warp speed’s strategy and approach. N Engl J Med. 2020;383:1701–03. doi:10.1056/NEJMp2027405.
   PubMed Web of Science ®Google Scholar
• WHO. Access to COVID-19 tools (ACT) accelerator. 2020.
   Google Scholar
• Gao Q, Bao L, Mao H, Wang L, Xu K, Yang M, Li Y, Zhu L, Wang N, Lv Z, et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science. 2020;369:77–81. doi:10.1126/science.abc1932.
   PubMed Web of Science ®Google Scholar
• Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, Plested JS, Zhu M, Cloney-Clark S, Zhou H, et al. Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N Engl J Med. 2020;383:2320–32. doi:10.1056/NEJMoa2026920.
   PubMed Web of Science ®Google Scholar
• Yang J, Wang W, Chen Z, Lu S, Yang F, Bi Z, Bao L, Mo F, Li X, Huang Y, et al. A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity. Nature. 2020;586:572–77. doi:10.1038/s41586-020-2599-8.
   PubMed Web of Science ®Google Scholar
• Li T, Zheng Q, Yu H, Wu D, Xue W, Xiong H, Huang X, Nie M, Yue M, Rong R, et al. SARS-CoV-2 spike produced in insect cells elicits high neutralization titres in non-human primates. Emerging Microbes Infect. 2020;9:2076–90. doi:10.1080/22221751.2020.1821583.
   PubMed Web of Science ®Google Scholar
• Pollet J, Chen WH, Strych U. Recombinant protein vaccines, a proven approach against coronavirus pandemics. Adv Drug Deliv Rev. 2021;170:71–82. doi:10.1016/j.addr.2021.01.001.
   PubMed Web of Science ®Google Scholar
• Chen WH, Tao X, Agrawal A, Algaissi A, Peng BH, Pollet J, Strych U, Bottazzi ME, Hotez PJ, Lustigman S, et al. Yeast-expressed SARS-CoV recombinant Receptor-Binding Domain (RBD219-N1) formulated with alum induces protective immunity and reduces immune enhancement. Vaccine. 2020;22:31232–39.
   Google Scholar
• Chen WH, Du L, Chag SM, Ma C, Tricoche N, Tao X, Seid CA, Hudspeth EM, Lustigman S, Tseng CTK, et al. Yeast-expressed recombinant protein of the receptor-binding domain in SARS-CoV spike protein with deglycosylated forms as a SARS vaccine candidate. Hum Vaccin Immunother. 2014;10:648–58. doi:10.4161/hv.27464.
   PubMed Web of Science ®Google Scholar
• Chen WH, Chag SM, Poongavanam MV, Biter AB, Ewere EA, Rezende W, Seid CA, Hudspeth EM, Pollet J, McAtee CP, et al. Optimization of the production process and characterization of the yeast-expressed SARS-CoV Recombinant Receptor-Binding Domain (RBD219-N1), a SARS vaccine candidate. J Pharm Sci. 2017;106:1961–70. doi:10.1016/j.xphs.2017.04.037.
   PubMed Web of Science ®Google Scholar
• Nyon MP, Du L, Tseng CK, Seid CA, Pollet J, Naceanceno KS, Agrawal A, Algaissi A, Peng B-H, Tai W, et al. Engineering a stable CHO cell line for the expression of a MERS-coronavirus vaccine antigen. Vaccine. 2018;36:1853–62. doi:10.1016/j.vaccine.2018.02.065.
   PubMed Web of Science ®Google Scholar
• CHICTR. Randomized double blind, placebo controlled phase I trial for anti novel coronavirus pneumonia (COVID-19) recombinant vaccine (Sf9). 2020. http://www.chictr.org.cn/showprojen.aspx?proj=64718
   Google Scholar
• Clinicaltrials_gov. KBP-201 COVID-19 Vaccine Trial in Healthy Volunteers. 2021.
   Google Scholar
• Clinicaltrials_gov. A Study to Evaluate the Safety and Immunogenicity of COVID-19 (AdimrSC-2f) Vaccine. 2021.
   Google Scholar
• Clinicaltrials_gov. Clinical Study of Recombinant Novel Coronavirus Vaccine. 2020.
   Google Scholar
• RPCEC. Soberano 01 - Estudio Fase I/II, aleatorizado, controlado, adaptativo, a doble ciego y multicéntrico para evaluar la seguridad, reactogenicidad e inmunogenicidad del Candidato Vacunal profiláctico FINLAY- FR-1 anti SARS – CoV – 2 en un esquema de dos dosis. (COVID-19). 2020.
   Google Scholar
• He Y, Zhou Y, Liu S, Kou Z, Li W, Farzan M, Jiang S. Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine. Biochem Biophys Res Commun. 2004;324:773–81. doi:10.1016/j.bbrc.2004.09.106.
   PubMed Web of Science ®Google Scholar
• Chen W-H, Wei J, Kundu RT, Adhikari R, Liu Z, Lee J, Versteeg L, Poveda C, Keegan B, Villar MJ, et al. Genetic modification to design a stable yeast-expressed recombinant SARS-CoV-2 receptor binding domain as a COVID-19 vaccine candidate. Biochimica et Biophysica Acta (BBA) - General Subjects 2021:129893. doi:10.1016/j.bbagen.2021.129893.
   Google Scholar
• Hotez PJ, Bottazzi ME. Developing a low-cost and accessible COVID-19 vaccine for global health. PLoS Negl Trop Dis. 2020;14:e0008548. doi:10.1371/journal.pntd.0008548.
   PubMed Web of Science ®Google Scholar
• Hotez PJ, Bottazzi ME, Singh SK, Brindley PJ, Will KS. COVID-19 become the next neglected tropical disease? PLoS Negl Trop Dis. 2020;14:e0008271. doi:10.1371/journal.pntd.0008271.
   PubMed Web of Science ®Google Scholar
• Millet JK, Whittaker GR. Murine Leukemia Virus (MLV)-based coronavirus spike-pseudotyped particle production and infection. Bio-protocol. 2016;6. doi:10.21769/BioProtoc.2035.
   PubMedGoogle Scholar
• Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. 2020;5:562–69. doi:10.1038/s41564-020-0688-y.
   PubMed Web of Science ®Google Scholar
• He J, Choe S, Walker R, Di Marzio P, Morgan DO, Landau NR. Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. J Virol. 1995;69:6705–11. doi:10.1128/JVI.69.11.6705-6711.1995.
   PubMed Web of Science ®Google Scholar
• Zufferey R, Nagy D, Mandel RJ, Naldini L, Trono D. Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol. 1997;15:871–75. doi:10.1038/nbt0997-871.
   PubMed Web of Science ®Google Scholar
• Jones K, Versteeg L, Damania A, Keegan B, Kendricks A, Pollet J, Cruz-Chan JV, Gusovsky F, Hotez PJ, Bottazzi ME, et al. Vaccine-linked chemotherapy improves benznidazole efficacy for acute Chagas disease. Infect Immun. 2018;86. doi:10.1128/IAI.00876-17.
   Web of Science ®Google Scholar
• Versteeg L, Le Guezennec X, Zhan B, Liu Z, Angagaw M, Woodhouse JD, Biswas S, Beaumier CM. Transferring Luminex(R) cytokine assays to a wall-less plate technology: validation and comparison study with plasma and cell culture supernatants. J Immunol Methods. 2017;440:74–82. doi:10.1016/j.jim.2016.11.003.
   PubMed Web of Science ®Google Scholar
• Schumann J, Stanko K, Schliesser U, Appelt C, Sawitzki B. Differences in CD44 surface expression levels and function discriminates IL-17 and IFN-gamma producing helper T cells. PLoS ONE. 2015;10:e0132479. doi:10.1371/journal.pone.0132479.
   PubMed Web of Science ®Google Scholar
• Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si H-R, Zhu Y, Li B, Huang C-L, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–73. doi:10.1038/s41586-020-2012-7.
   PubMed Web of Science ®Google Scholar
• Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu N-H, Nitsche A, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–80 e8. doi:10.1016/j.cell.2020.02.052.
   PubMed Web of Science ®Google Scholar
• Lee J, Liu Z, Chen WH, Wei J, Kundu R, Adhikari R, Rivera JA, Gillespie PM, Strych U, Zhan B, et al. Process development and scale-up optimization of the SARS-CoV-2 receptor binding domain-based vaccine candidate, RBD219-N1C1. biorxiv. 2021. 10.1101/2020.12.30.424829v1.
   Google Scholar
• Hotez PJ, Bottazzi ME, Corry DB. The potential role of Th17 immune responses in coronavirus immunopathology and vaccine-induced immune enhancement. Microbes Infect. 2020;22:165–67. doi:10.1016/j.micinf.2020.04.005.
   PubMed Web of Science ®Google Scholar
• Liu L, Wang P, Nair MS, Yu J, Rapp M, Wang Q, Luo Y, Chan JFW, Sahi V, Figueroa A, et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature. 2020;584:450–56. doi:10.1038/s41586-020-2571-7.
   PubMed Web of Science ®Google Scholar
• Karlsson AC, Humbert M, Buggert M. The known unknowns of T cell immunity to COVID-19. Sci Immunol. 2020;5:eabe8063. doi:10.1126/sciimmunol.abe8063.
   PubMed Web of Science ®Google Scholar
• Hotez PJ, Corry DB, Strych U, Bottazzi ME. COVID-19 vaccines: neutralizing antibodies and the alum advantage. Nat Rev Immunol. 2020;20:399–400. doi:10.1038/s41577-020-0358-6.
   PubMed Web of Science ®Google Scholar
• Haynes BF, Corey L, Fernandes P, Gilbert PB, Hotez PJ, Rao S, Santos MR, Schuitemaker H, Watson M, Arvin A, et al. Prospects for a safe COVID-19 vaccine. Sci Transl Med. 2020;12:eabe0948. doi:10.1126/scitranslmed.abe0948.
   PubMed Web of Science ®Google Scholar
• Liang JG, Su D, Song TZ, Zeng Y, Huang W, Wu J, Xu R, Luo P, Yang X, Zhang X, et al. S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates. Nat Commun. 2021;12:1346. https://doi.org/10.1038/s41467-021-21634-1
   Google Scholar
• Clinicaltrials_gov. SCB-2019 as COVID-19 Vaccine. 2020.
   Google Scholar
• Genetic_Engineering&Biotechnology_News. COVAXX – UB-612. 2020.
   Google Scholar
• Clinicaltrials_gov. A Study to Evaluate the Safety and Immunogenicity of MVC-COV1901 Against COVID-19. 2020.
   Google Scholar
• Clinicaltrials_gov. Study of the Safety, Reactogenicity and Immunogenicity of “EpiVacCorona” Vaccine for the Prevention of COVID-19 (EpiVacCorona). 2020.
   Google Scholar
• Clinicaltrials_gov. A Study to Evaluate the Safety, Tolerability, and Immunogenicity of UB-612 COVID-19 Vaccine. 2020.
   Google Scholar
• Kuo TY, Lin MY, Coffman RL, Campbell JD, Traquina P, Lin YJ, Liu LTC, Cheng J, Wu Y-C, Wu -C-C, et al. Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19. Sci Rep. 2020;10:20085. doi:10.1038/s41598-020-77077-z.
   PubMed Web of Science ®Google Scholar
• Garry RF. Mutations arising in SARS-CoV-2 spike on sustained human-to-human transmission and human-to-animal passage. Virologicalorg. 2021. https://virological.org/t/mutations-arising-in-sars-cov-2-spike-on-sustained-human-to-human-transmission-and-human-to-animal-passage/578
   Google Scholar
• Draper SJ, Biswas S, Spencer AJ, Remarque EJ, Capone S, Naddeo M, Dicks MDJ, Faber BW, De Cassan SC, Folgori A, et al. Enhancing blood-stage malaria subunit vaccine immunogenicity in rhesus macaques by combining adenovirus, poxvirus, and protein-in-adjuvant vaccines. J Immunol. 2010;185:7583–95. doi:10.4049/jimmunol.1001760.
   PubMed Web of Science ®Google Scholar
• Hodgson SH, Choudhary P, Elias SC, Milne KH, Rampling TW, Biswas S, Poulton ID, Miura K, Douglas AD, Alanine DG, et al. Combining viral vectored and protein-in-adjuvant vaccines against the blood-stage malaria antigen AMA1: report on a phase 1a clinical trial. Mol Ther. 2014;22:2142–54. doi:10.1038/mt.2014.157.
   PubMed Web of Science ®Google Scholar
• Gov.UK. World-first COVID-19 alternating dose vaccine study launches in UK. 2021.
   Google Scholar
• Van Doremalen N, Lambe T, Spencer A, Belij-Rammerstorfer S, Purushotham JN, Port JR, Avanzato VA, Bushmaker T, Flaxman A, Ulaszewska M, et al. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques. Nature. 2020;586:578–82. doi:10.1038/s41586-020-2608-y.
   PubMed Web of Science ®Google Scholar
• Sadoff J, De Paepe E, Haazen W, Omoruyi E, Bastian AR, Comeaux C, Heijnen E, Strout C, Schuitemaker H, Callendret B. Safety and immunogenicity of the Ad26.RSV.preF investigational vaccine coadministered with an influenza vaccine in older adults. J Infect Dis. 2020;222:979–88. doi:10.1093/infdis/jiaa193.
   PubMedGoogle Scholar
• Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, Bellamy D, Bibi S, Bittaye M, Clutterbuck EA, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020;396:467–78. doi:10.1016/S0140-6736(20)31604-4.
   PubMed Web of Science ®Google Scholar
• Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, McCullough MP, Chappell JD, Denison MR, Stevens LJ, et al. An mRNA vaccine against SARS-CoV-2 - preliminary report. N Engl J Med. 2020;383:1920–31. doi:10.1056/NEJMoa2022483.
   PubMed Web of Science ®Google Scholar
• Corbett KS, Edwards DK, Leist SR, Abiona OM, Boyoglu-Barnum S, Gillespie RA, Himansu S, Schäfer A, Ziwawo CT, DiPiazza AT, et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature. 2020;586:567–71. doi:10.1038/s41586-020-2622-0.
   PubMed Web of Science ®Google Scholar
• Walsh EE, Frenck RW Jr., Falsey AR, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Mulligan MJ, Bailey R, et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med. 2020;383:2439–50. doi:10.1056/NEJMoa2027906.
   PubMed Web of Science ®Google Scholar
• Hotez PJ, Bottazzi ME. Developing a low-cost and accessible COVID-19 vaccine for global health. Preprintsorg. PLoS Negl Trop Dis. 2020;14(7):e0008548.
   Google Scholar
• WHO. Prequalified Vaccines. 2020.
   Google Scholar
• CTRI. Biological E’s novel Covid-19 vaccine of SARS-CoV-2 for protection against Covid-19 disease. 2020. http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=48329&EncHid=&modid=&compid=%27,%2748329det%27
   Google Scholar