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Review

State of the Art in Epitope Mapping and Opportunities in COVID-19

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Article: FSO832 | Received 29 Jul 2022, Accepted 15 Feb 2023, Published online: 06 Mar 2023

References

  • Sanchez-TrincadoJL , Gomez-PerosanzM , RechePA. Fundamentals and Methods for T- and B-Cell Epitope Prediction. Journal of Immunology Research2017, 2680160 (2017).
  • YangX , YuX. An introduction to epitope prediction methods and software. Reviews in Medical Virology19(2), 77–96 (2009).
  • Palatnik-De-SousaCB , SoaresIDS , RosaDS. Editorial: Epitope Discovery and Synthetic Vaccine Design. Frontiers in Immunology9, 1–3 (2018).
  • KozlovaEEG , ViartBT , DeAvila RaM , FelicoriLF , Chavez-OlorteguiC. Classification epitopes in groups based on their protein family. BMC Bioinformatics16(19), S7 (2015).
  • GuoJ-Y , LiuIJ , LinH-Tet al.Identification of COVID-19 B-cell epitopes with phage-displayed peptide library. Journal of Biomedical Science28(1), 43 (2021).
  • KarT , NarsariaU , BasakSet al.A candidate multi-epitope vaccine against SARS-CoV-2. Sci Rep10(1), 10895 (2020).
  • CameriniD , RandallAZ , Trappl-KimmonsKet al.Mapping SARS-CoV-2 Antibody Epitopes in COVID-19 Patients with a Multi-Coronavirus Protein Microarray. Microbiol Spectr9(2), e0141621 (2021).
  • ZhangBZ , HuYF , ChenLLet al.Mining of epitopes on Spike protein of SARS-CoV-2 from COVID-19 patients. Cell Res30(8), 702–704 (2020).
  • HuangJ , HondaW. CED: a conformational epitope database. BMC Immunology7(1), 7 (2006).
  • SunJ , XuT , WangS , LiG , WuD , CaoZ. Does difference exist between epitope and non-epitope residues? Analysis of the physicochemical and structural properties on conformational epitopes from B-cell protein antigens. Immunome research7, 1–11 (2011).
  • CruseJM , LewisRE , WangH. 2 - Antigens, Immunogens, Vaccines, and Immunization. In: Immunology Guidebook.Academic Press San Diego, 17–45 (2004).
  • LuštrekM , LorenzP , KreutzerMet al.Epitope Predictions Indicate the Presence of Two Distinct Types of Epitope-Antibody-Reactivities Determined by Epitope Profiling of Intravenous Immunoglobulins. PLOS ONE8(11), e78605 (2013).
  • DavisMM , AltmanJD , NewellEW. Interrogating the repertoire: broadening the scope of peptide-MHC multimer analysis. Nat Rev Immunol11(8), 551–558 (2011).
  • BakkerAH , SchumacherTNM. MHC multimer technology: current status and future prospects. Curr. Opin. Immunol.17(4), 428–433 (2005).
  • CecconiV , MoroM , DelMare S , DellabonaP , CasoratiG. Use of MHC class II tetramers to investigate CD4+ T cell responses: problems and solutions. Cytometry A.73A(11), 1010–1018 (2008).
  • MolonyRD , RiceJM , YukJSet al.Mining the Salivary Proteome with Grating-Coupled Surface Plasmon Resonance Imaging and Surface Plasmon Coupled Emission Microarrays. Curr Protoc Toxicol.53(1), 18.16.11–18.16.19 (2012).
  • AhmadTA , EweidaAE , El-SayedLH. T-cell epitope mapping for the design of powerful vaccines. Vaccine Reports6, 13–22 (2016).
  • WuC-H , LiuIJ , LuR-M , WuH-C. Advancement and applications of peptide phage display technology in biomedical science. Journal of Biomedical Science23(1), 8 (2016).
  • StoneJD , DemkowiczWE , SternLJ. HLA-restricted epitope identification and detection of functional T cell responses by using MHC–peptide and costimulatory microarrays. Proc Natl Acad Sci USA.102(10), 3744–3749 (2005).
  • LetschA , ScheibenbogenC. Quantification and characterization of specific T-cells by antigen-specific cytokine production using ELISPOT assay or intracellular cytokine staining. Methods31(2), 143–149 (2003).
  • SederRA , DarrahPA , RoedererM. T-cell quality in memory and protection: implications for vaccine design. Nature Reviews Immunology8(4), 247–258 (2008).
  • ClayTM , HobeikaAC , MoscaPJ , LyerlyHK , MorseMA. Assays for monitoring cellular immune responses to active immunotherapy of cancer. Clinical cancer research: an official journal of the American Association for Cancer Research7(5), 1127–1135 (2001).
  • MalyguineAM , StroblS , DunhamK , ShurinMR , SayersTJ. ELISPOT Assay for Monitoring Cytotoxic T Lymphocytes (CTL) Activity in Cancer Vaccine Clinical Trials. Cells1(2), 111–126 (2012).
  • BowyerG , RamplingT , PowlsonJet al.Activation-induced Markers Detect Vaccine-Specific CD4+ T Cell Responses Not Measured by Assays Conventionally Used in Clinical Trials. Vaccines (Basel)6(3), 50 (2018).
  • MalherbeL. T-cell epitope mapping. Annals of Allergy, Asthma & Immunology103(1), 76–79 (2009).
  • IsmailN , OlanoJP , FengH-M , WalkerDH. Current status of immune mechanisms of killing of intracellular microorganims. FEMS Microbiol. Lett.207(2), 111–120 (2002).
  • HohdatsuT , YamatoH , OhkawaTet al.Vaccine efficacy of a cell lysate with recombinant baculovirus-expressed feline infectious peritonitis (FIP) virus nucleocapsid protein against progression of FIP. Veterinary Microbiology97(1), 31–44 (2003).
  • AhmadTA , EweidaAE , SheweitaSA. B-cell epitope mapping for the design of vaccines and effective diagnostics. Trials in Vaccinology5, 71–83 (2016).
  • GershoniJM , Roitburd-BermanA , Siman-TovDD , TarnovitskiFreund N , WeissY. Epitope mapping: the first step in developing epitope-based vaccines. BioDrugs: clinical immunotherapeutics, biopharmaceuticals and gene therapy21(3), 145–156 (2007).
  • HjelmB. Epitope mapping of antibodies towards human protein targets [PhD thesis].Royal Institute of Technology School of Biotechnology,Stockholm (2011).
  • LiN , LiZ , FuY , CaoS. Cryo-EM Studies of Virus-Antibody Immune Complexes. Virologica Sinica35(1), 1–13 (2020).
  • Baerga-OrtizA , HughesCA , MandellJG , KomivesEA. Epitope mapping of a monoclonal antibody against human thrombin by H/D-exchange mass spectrometry reveals selection of a diverse sequence in a highly conserved protein. Protein science: a publication of the Protein Society11(6), 1300–1308 (2002).
  • SuckauD , KöhlJ , KarwathGet al.Molecular epitope identification by limited proteolysis of an immobilized antigen-antibody complex and mass spectrometric peptide mapping. Proc Natl Acad Sci USA.87(24), 9848–9852 (1990).
  • ReinekeU , SchutkowskiM. Epitope mapping protocols.Springer, 1 (2009).
  • KumadaY , KatohS , ImanakaH , ImamuraK , NakanishiK. Development of a one-step ELISA method using an affinity peptide tag specific to a hydrophilic polystyrene surface. Journal of Biotechnology127(2), 288–299 (2007).
  • NiegowskaM , PaccagniniD , MannuC , TarghettaC , SonginiM , SechiLA. Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies. Journal of Diabetes Research2016, 5842701 (2016).
  • MullettWM , LaiEPC , YeungJM. Surface Plasmon Resonance-Based Immunoassays. Methods (San Diego, Calif.)22(1), 77–91 (2000).
  • BrogioniB , BertiF. Surface plasmon resonance for the characterization of bacterial polysaccharide antigens: a review. MedChemComm5(8), 1058–1066 (2014).
  • PausD , WinterG. Mapping epitopes and antigenicity by site-directed masking. Proc Natl Acad Sci USA.103(24), 9172–9177 (2006).
  • LafuenteEM , RechePA. Prediction of MHC–peptide binding: a systematic and comprehensive overview. Current pharmaceutical design15(28), 3209–3220 (2009).
  • JensenPE. Recent advances in antigen processing and presentation. Nat Immunol8(10), 1041–1048 (2007).
  • PatronovA , DoytchinovaI. T-cell epitope vaccine design by immunoinformatics. Open Biol.3(1), 120139 (2013).
  • MartinW , SbaiH , DeGroot AS. Bioinformatics tools for identifying class I-restricted epitopes. Methods29(3), 289–298 (2003).
  • WangP , SidneyJ , DowC , MothéB , SetteA , PetersB. A systematic assessment of MHC class II peptide binding predictions and evaluation of a consensus approach. PLoS computational biology4(4), e1000048–e1000048 (2008).
  • GalanisKA , NastouKC , PapandreouNC , PetichakisGN , PigisDG , IconomidouVA. Linear B-Cell Epitope Prediction for In Silico Vaccine Design: A Performance Review of Methods Available via Command-Line Interface. Int J Mol Sci.22(6), 3210 (2021).
  • DesaiDV , Kulkarni-KaleU. T-cell epitope prediction methods: an overview. Methods in molecular biology (Clifton, N.J.)1184, 333–364 (2014).
  • ChukwudozieOS , GrayCM , FagbayiTAet al.Immuno-informatics design of a multimeric epitope peptide based vaccine targeting SARS-CoV-2 Spike glycoprotein. PLOS ONE16(3), e0248061 (2021).
  • PotocnakovaL , BhideM , PulzovaLB. An Introduction to B-Cell Epitope Mapping and In Silico Epitope Prediction. Journal of immunology research2016, 6760830–6760830 (2016).
  • KringelumJV , LundegaardC , LundO , NielsenM. Reliable B cell epitope predictions: impacts of method development and improved benchmarking. PLoS Comput Biol8(12), e1002829 (2012).
  • SakrMM , ElsayedNS , El-HousseinyGS. Latest updates on SARS-CoV-2 genomic characterization, drug, and vaccine development; a comprehensive bioinformatics review. Microb. Pathog.154, 104809 (2021).
  • Farrera-SolerL , DaguerJP , BarluengaSet al.Identification of immunodominant linear epitopes from SARS-CoV-2 patient plasma. PLOS ONE15(9), e0238089 (2020).
  • WanJ , XingS , DingLet al.Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection. Cell Rep32(3), 107918 (2020).
  • WangD , MaiJ , ZhouWet al.Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design. Vaccines (Basel)8(3), 355 (2020).
  • LiY , MaML , LeiQet al.Linear epitope landscape of the SARS-CoV-2 Spike protein constructed from 1,051 COVID-19 patients. Cell Rep34(13), 108915 (2021).
  • HaynesWA , KamathK , BozekowskiJet al.High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19. Commun Biol4(1), 1317 (2021).
  • LiY , LaiDY , ZhangHNet al.Linear epitopes of SARS-CoV-2 Spike protein elicit neutralizing antibodies in COVID-19 patients. Cell Mol Immunol17(10), 1095–1097 (2020).
  • PohCM , CarissimoG , WangBet al.Two linear epitopes on the SARS-CoV-2 Spike protein that elicit neutralising antibodies in COVID-19 patients. Nat Commun11(1), 2806 (2020).
  • VitaR , MahajanS , OvertonJAet al.The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res.47(D1), D339–D343 (2019).
  • FarkasC , MellaA , TurgeonM , HaighJJ. A Novel SARS-CoV-2 Viral Sequence Bioinformatic Pipeline Has Found Genetic Evidence That the Viral 3′ Untranslated Region (UTR) Is Evolving and Generating Increased Viral Diversity. Front Microbiol12, 665041 (2021).
  • KoyamaT , PlattD , ParidaL. Variant analysis of SARS-CoV-2 genomes. Bull World Health Organ98(7), 495–504 (2020).
  • VolzE , HillV , MccroneJTet al.Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity. Cell184(1), 64–75e11 (2021).
  • ToyoshimaY , NemotoK , MatsumotoS , NakamuraY , KiyotaniK. SARS-CoV-2 genomic variations associated with mortality rate of COVID-19. J Hum Genet65(12), 1075–1082 (2020).
  • PolyiamK , PhoolcharoenW , ButkhotNet al.Immunodominant linear B cell epitopes in the Spike and membrane proteins of SARS-CoV-2 identified by immunoinformatics prediction and immunoassay. Sci Rep11(1), 20383 (2021).
  • BahnanW , WrightonS , SundwallMet al.Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2. Front Immunol12, 808932 (2021).
  • Beaudoin-BussieresG , ChenY , UllahIet al.A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection. Cell Rep38(7), 110368 (2022).
  • SteffenTL , StoneET , HassertMet al.The receptor binding domain of SARS-CoV-2 Spike is the key target of neutralizing antibody in human polyclonal sera. J bioRxiv doi:10.1101/2020.08.21.261727 (2020).
  • PiccoliL , ParkYJ , TortoriciMAet al.Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology. Cell183(4), 1024–1042e1021 (2020).
  • WangH , WuX , ZhangXet al.SARS-CoV-2 Proteome Microarray for Mapping COVID-19 Antibody Interactions at Amino Acid Resolution. ACS Cent Sci6(12), 2238–2249 (2020).
  • ShrockE , FujimuraE , KulaTet al.Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity. Science370(6520), eabd4250 (2020).
  • LuS , XieXX , ZhaoLet al.The immunodominant and neutralization linear epitopes for SARS-CoV-2. Cell Rep34(4), 108666 (2021).
  • JiangM , ZhangG , LiuHet al.Epitope Profiling Reveals the Critical Antigenic Determinants in SARS-CoV-2 RBD-Based Antigen. Front Immunol12, 707977 (2021).
  • LiangT , ChengM , TengFet al.Proteome-wide epitope mapping identifies a resource of antibodies for SARS-CoV-2 detection and neutralization. Signal Transduct Target Ther6(1), 166 (2021).
  • HuangY , YangC , XuXF , XuW , LiuSW. Structural and functional properties of SARS-CoV-2 Spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin41(9), 1141–1149 (2020).
  • LiuL , WangP , NairMSet al.Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 Spike. Nature584(7821), 450–456 (2020).
  • YamayoshiS , YasuharaA , ItoMet al.Antibody titers against SARS-CoV-2 decline, but do not disappear for several months. EClinicalMedicine32, 100734 (2021).
  • ShahVK , FirmalP , AlamA , GangulyD , ChattopadhyayS. Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past. Front Immunol11, 1949 (2020).
  • SainiSK , HersbyDS , TamhaneTet al.SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8(+) T cell activation in COVID-19 patients. Sci Immunol6(58), eabf7550 (2021).
  • TarkeA , SidneyJ , KiddCKet al.Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases. Cell Rep Med2(2), 100204 (2021).
  • WilsonEA , HirneiseG , SingharoyA , AndersonKS. Total predicted MHC-I epitope load is inversely associated with population mortality from SARS-CoV-2. Cell Rep Med2(3), 100221 (2021).
  • MorsyS , MorsyA. Epitope mimicry analysis of SARS-COV-2 surface proteins and human lung proteins. J Mol Graph Model105, 107836 (2021).
  • KanducD. From Anti-SARS-CoV-2 Immune Response to the Cytokine Storm via Molecular Mimicry. Antibodies (Basel)10(4), 36 (2021).
  • NgKW , FaulknerN , CornishGHet al.Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science370(6522), 1339–1343 (2020).
  • Obando-PeredaG. Can molecular mimicry explain the cytokine storm of SARS-CoV-2?: an in silico approach. J. Med. Virol.93(9), 5350–5357 (2021).
  • PanP , ShenM , YuZet al.SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. Nat Commun12(1), 4664 (2021).
  • ChengMH , ZhangS , PorrittRAet al.Superantigenic character of an insert unique to SARS-CoV-2 Spike supported by skewed TCR repertoire in patients with hyperinflammation. Proc Natl Acad Sci U S A117(41), 25254–25262 (2020).
  • Garcia-BeltranWF , LamEC , StDenis Ket al.Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell184(9), 2523 (2021).
  • WHO. Tracking SARS-CoV-2 Variants. https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/ (March 2022).
  • StarrTN , GreaneyAJ , HiltonSKet al.Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. bioRxiv182(5), 1295–1310e20 doi:10.1101/2020.06.17.157982 (2020).
  • Rodriguez-RivasJ , CroceG , MuscatM , WeigtM. Epistatic models predict mutable sites in SARS-CoV-2 proteins and epitopes. Proc Natl Acad Sci U S A119(4), e2113118119 (2022).
  • WangY , LiuM , ShenYet al.Novel sarbecovirus bispecific neutralizing antibodies with exceptional breadth and potency against currently circulating SARS-CoV-2 variants and sarbecoviruses. Cell Discov8(1), 36 (2022).
  • GreaneyAJ , LoesAN , CrawfordKHDet al.Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host Microbe29(3), 463–476e466 (2021).
  • DeSilva TI , LiuG , LindseyBBet al.The impact of viral mutations on recognition by SARS-CoV-2 specific T cells. iScience24(11), 103353 (2021).
  • VianaR , MoyoS , AmoakoDGet al.Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa. Nature603(7902), 679–686 (2022).
  • NaranbhaiV , NathanA , KasekeCet al.T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals. Cell185(6), 1041–1051e1046 (2022).
  • KeetonR , TinchoMB , NgomtiAet al.T cell responses to SARS-CoV-2 Spike cross-recognize Omicron. Nature603(7901), 488–492 (2022).
  • CameroniE , BowenJE , RosenLEet al.Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. Nature602(7898), 664–670 (2022).
  • HerrscherC , EymieuxS , GaboritCet al.ELISA-Based Analysis Reveals an Anti-SARS-CoV-2 Protein Immune Response Profile Associated with Disease Severity. J Clin Med11(2), 405 (2022).
  • AgererB , KoblischkeM , GudipatiVet al.SARS-CoV-2 mutations in MHC-I-restricted epitopes evade CD8(+) T cell responses. Sci Immunol6(57), eabg6461 (2021).
  • MoodyR , WilsonKL , BoerJCet al.Predicted B Cell Epitopes Highlight the Potential for COVID-19 to Drive Self-Reactive Immunity. Frontiers in Bioinformatics1, 709533 (2021).
  • KiddM , RichterA , BestAet al.S-Variant SARS-CoV-2 Lineage B1.1.7 Is Associated With Significantly Higher Viral Load in Samples Tested by TaqPath Polymerase Chain Reaction. J. Infect. Dis.223(10), 1666–1670 (2021).
  • ZhaoS , LouJ , CaoLet al.Quantifying the transmission advantage associated with N501Y substitution of SARS-CoV-2 in the UK: an early data-driven analysis. J Travel Med28(2), taab011 (2021).
  • HamedSM , ElkhatibWF , KhairallaAS , NoreddinAM. Global dynamics of SARS-CoV-2 clades and their relation to COVID-19 epidemiology. Sci Rep11(1), 8435 (2021).
  • ChenRE , ZhangX , CaseJBet al.Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med.27(4), 717–726 (2021).
  • WangP , NairMS , LiuLet al.Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature593(7857), 130–135 (2021).
  • MoxonR , RechePA , RappuoliR. Editorial: Reverse Vaccinology. Front Immunol10, 2776 (2019).
  • ZhangG , LiJ , AiG , HeJ , WangC , FengJ. A new intrinsic aminoglycoside 6′-N-acetyltransferase subclass, AAC(6′)-III, in Burkholderia pseudomallei, Burkholderia mallei and Burkholderia oklahomensis. J. Antimicrob. Chemother.75(5), 1352–1353 (2020).
  • ParvizpourS , PourseifMM , RazmaraJ , RafiMA , OmidiY. Epitope-based vaccine design: a comprehensive overview of bioinformatics approaches. Drug Discov. Today25(6), 1034–1042 (2020).
  • NazA , ShahidF , ButtTT , AwanFM , AliA , MalikA. Designing Multi-Epitope Vaccines to Combat Emerging Coronavirus Disease 2019 (COVID-19) by Employing Immuno-Informatics Approach. Front Immunol11, 1663 (2020).
  • BukhariSNH , JainA , HaqE , MehbodniyaA , WebberJ. Machine Learning Techniques for the Prediction of B-Cell and T-Cell Epitopes as Potential Vaccine Targets with a Specific Focus on SARS-CoV-2 Pathogen: A Review. Pathogens11(2), 146 (2022).
  • SmithCC , OlsenKS , GentryKMet al.Landscape and selection of vaccine epitopes in SARS-CoV-2. Genome Med13(1), 101 (2021).
  • VabretN. Antibody responses to SARS-CoV-2 short-lived. Nat Rev Immunol20(9), 519 (2020).
  • DanJM , MateusJ , KatoYet al.Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science371(6529), eabf4063 (2021).
  • FillMalfertheiner S , BrandstetterS , RothSet al.Immune response to SARS-CoV-2 in health care workers following a COVID-19 outbreak: a prospective longitudinal study. J Clin Virol130, 104575 (2020).
  • WajnbergA , AmanatF , FirpoAet al.Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science370(6521), 1227–1230 (2020).
  • GudbjartssonDF , NorddahlGL , MelstedPet al.Humoral Immune Response to SARS-CoV-2 in Iceland. N. Engl. J. Med.383(18), 1724–1734 (2020).
  • CiabattiniA , PastoreG , FiorinoFet al.Evidence of SARS-CoV-2-Specific Memory B Cells Six Months After Vaccination With the BNT162b2 mRNA Vaccine. Front Immunol12, 740708 (2021).
  • SnyderTM , GittelmanRM , KlingerMet al.Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels. medRxiv doi:10.1101/2020.07.31.20165647 (2020).
  • PanagiotiE , KlenermanP , LeeLN , VanDer Burg SH , ArensR. Features of Effective T Cell-Inducing Vaccines against Chronic Viral Infections. Front Immunol9, 276 (2018).
  • KeetonR , RichardsonSI , Moyo-GweteTet al.Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner. Cell Host Microbe29(11), 1611–1619e1615 (2021).
  • RiouC , KeetonR , Moyo-GweteTet al.Escape from recognition of SARS-CoV-2 variant Spike epitopes but overall preservation of T cell immunity. Sci Transl Med14(631), eabj6824 (2022).
  • TarkeA , SidneyJ , MethotNet al.Impact of SARS-CoV-2 variants on the total CD4(+) and CD8(+) T cell reactivity in infected or vaccinated individuals. Cell Rep Med2(7), 100355 (2021).
  • CunY , LiC , ShiLet al.COVID-19 coronavirus vaccine T cell epitope prediction analysis based on distributions of HLA class I loci (HLA-A, -B, -C) across global populations. Hum Vaccin Immunother17(4), 1097–1108 (2021).
  • MazzoccoG , NiemiecI , MyronovAet al.AI Aided Design of Epitope-Based Vaccine for the Induction of Cellular Immune Responses Against SARS-CoV-2. Front Genet12, 602196 (2021).
  • HeitmannJS , BilichT , TandlerCet al.A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity. Nature601(7894), 617–622 (2022).
  • CrookeSN , OvsyannikovaIG , KennedyRB , PolandGA. Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome. Sci Rep10(1), 14179 (2020).
  • FengY , JiangH , QiuMet al.Multi-Epitope Vaccine Design Using an Immunoinformatic Approach for SARS-CoV-2. Pathogens10(6), 737 (2021).
  • GrifoniA , SidneyJ , ZhangY , ScheuermannRH , PetersB , SetteA. A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2. Cell Host Microbe27(4), 671–680e672 (2020).
  • FatobaAJ , MaharajL , AdelekeVT , OkpekuM , AdeniyiAA , AdelekeMA. Immunoinformatics prediction of overlapping CD8(+) T-cell, IFN-gamma and IL-4 inducer CD4(+) T-cell and linear B-cell epitopes based vaccines against COVID-19 (SARS-CoV-2). Vaccine39(7), 1111–1121 (2021).
  • KhanMT , IslamMJ , PariharAet al.Immunoinformatics and molecular modeling approach to design universal multi-epitope vaccine for SARS-CoV-2. Inform Med Unlocked24, 100578 (2021).
  • GrifoniA , WeiskopfD , RamirezSIet al.Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell181(7), 1489–1501e1415 (2020).
  • PengY , MentzerAJ , LiuGet al.Broad and strong memory CD4 (+) and CD8 (+) T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients. bioRxiv doi:10.1101/2020.06.05.134551 (2020).
  • BraunJ , LoyalL , FrentschMet al.SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19. Nature587(7833), 270–274 (2020).
  • Vider-ShalitT , RaffaeliS , LouzounY. Virus-epitope vaccine design: informatic matching the HLA-I polymorphism to the virus genome. Mol. Immunol.44(6), 1253–1261 (2007).
  • DeviYD , GoswamiHB , KonwarSet al.Immunoinformatics mapping of potential epitopes in SARS-CoV-2 structural proteins. PLOS ONE16(11), e0258645 (2021).
  • ConfortiA , MarraE , PalomboFet al.COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models. Mol Ther30(1), 311–326 (2022).
  • HotezPJ , CorryDB , BottazziME. COVID-19 vaccine design: the Janus face of immune enhancement. Nat Rev Immunol20(6), 347–348 (2020).
  • HuismanW , MartinaBE , RimmelzwaanGF , GrutersRA , OsterhausAD. Vaccine-induced enhancement of viral infections. Vaccine27(4), 505–512 (2009).
  • GustianandaM , SulistyoBP , AgustriawanD , AndariniS. Immunoinformatics Analysis of SARS-CoV-2 ORF1ab Polyproteins to Identify Promiscuous and Highly Conserved T-Cell Epitopes to Formulate Vaccine for Indonesia and the World Population. Vaccines (Basel)9(12), 1459 (2021).
  • AlamA , KhanA , ImamNet al.Design of an epitope-based peptide vaccine against the SARS-CoV-2: a vaccine-informatics approach. Brief Bioinform22(2), 1309–1323 (2021).
  • TahirUl Qamar M , RehmanA , TusleemKet al.Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: immunoinformatics and in silico approaches. PLOS ONE15(12), e0244176 (2020).
  • JyotishaSingh S , QureshiIA. Multi-epitope vaccine against SARS-CoV-2 applying immunoinformatics and molecular dynamics simulation approaches. J Biomol Struct Dyn40(7), 2917–2933 (2022).
  • YangH , CaoJ , LinXet al.Developing an Effective Peptide-Based Vaccine for COVID-19: Preliminary Studies in Mice Models. Viruses.14(3), 449 (2022).
  • LiangQ , WangY , ZhangSet al.RBD trimer mRNA vaccine elicits broad and protective immune responses against SARS-CoV-2 variants. iScience25(4), 104043 (2022).
  • WeinreichDM , SivapalasingamS , NortonTet al.REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N. Engl. J. Med.384(3), 238–251 (2021).
  • ChapmanAP , TangX , LeeJRet al.Rapid development of neutralizing and diagnostic SARS-COV-2 mouse monoclonal antibodies. Sci Rep11(1), 9682 (2021).
  • LiL , ZhangW , HuYet al.Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. JAMA324(5), 460–470 (2020).
  • SalazarE , PerezKK , AshrafMet al.Treatment of Coronavirus Disease 2019 (COVID-19) Patients with Convalescent Plasma. Am. J. Pathol.190(8), 1680–1690 (2020).
  • KimC , RyuDK , LeeJet al.A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 Spike protein. Nat Commun12(1), 288 (2021).
  • CortiD , PurcellLA , SnellG , VeeslerD. Tackling COVID-19 with neutralizing monoclonal antibodies. Cell184(12), 3086–3108 (2021).
  • NelsonPN , ReynoldsGM , WaldronEE , WardE , GiannopoulosK , MurrayPG. Monoclonal antibodies. Mol Pathol53(3), 111–117 (2000).
  • CaoY , SuB , GuoXet al.Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells. Cell182(1), 73–84e16 (2020).
  • BaumA , FultonBO , WlogaEet al.Antibody cocktail to SARS-CoV-2 Spike protein prevents rapid mutational escape seen with individual antibodies. Science369(6506), 1014–1018 (2020).
  • XieJ , DingC , HeJet al.Novel Monoclonal Antibodies and Recombined Antibodies Against Variant SARS-CoV-2. Front Immunol12, 715464 (2021).
  • ZostSJ , GilchukP , CaseJBet al.Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature584(7821), 443–449 (2020).
  • BrouwerPJM , CanielsTG , VanDer Straten Ket al.Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science369(6504), 643–650 (2020).
  • UenoM , Iwata-YoshikawaN , MatsunagaAet al.Isolation of human monoclonal antibodies with neutralizing activity to a broad spectrum of SARS-CoV-2 viruses including the Omicron variants. Antiviral Res.201, 105297 doi:10.1016/j.antiviral.2022.105297 (2022).
  • PiepenbrinkMS , ParkJG , OladunniFSet al.Therapeutic activity of an inhaled potent SARS-CoV-2 neutralizing human monoclonal antibody in hamsters. Cell Rep Med2(3), 100218 (2021).
  • ShanS , MokCK , ZhangSet al.A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants. Front Immunol12, 766821 (2021).
  • YuanM , WuNC , ZhuXet al.A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV. Science368(6491), 630–633 (2020).
  • PintoD , ParkYJ , BeltramelloMet al.Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature583(7815), 290–295 (2020).
  • HansenJ , BaumA , PascalKEet al.Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science369(6506), 1010–1014 (2020).
  • KovacechB , FialovaL , FilipcikPet al.Monoclonal antibodies targeting two immunodominant epitopes on the Spike protein neutralize emerging SARS-CoV-2 variants of concern. EBioMedicine76, 103818 (2022).
  • TaiW , ZhangX , HeY , JiangS , DuL. Identification of SARS-CoV RBD-targeting monoclonal antibodies with cross-reactive or neutralizing activity against SARS-CoV-2. Antiviral Res.179, 104820 (2020).
  • LaiGC , ChaoTL , LinSYet al.Neutralization or enhancement of SARS-CoV-2 infection by a monoclonal antibody targeting a specific epitope in the Spike receptor-binding domain. Antiviral Res.200, 105290 (2022).
  • YuanTZ , GargP , WangLet al.Rapid discovery of diverse neutralizing SARS-CoV-2 antibodies from large-scale synthetic phage libraries. MAbs14(1), 2002236 (2022).
  • TanTH , PattonE , MunroCA , Corzo-LeonDE , PorterAJ , PalliyilS. Monoclonal Human Antibodies That Recognise the Exposed N and C Terminal Regions of the Often-Overlooked SARS-CoV-2 ORF3a Transmembrane Protein. Viruses13(11), 2201 (2021).
  • ParrayHA , ChiranjiviAK , AsthanaSet al.Identification of an anti-SARS-CoV-2 receptor-binding domain-directed human monoclonal antibody from a naive semisynthetic library. J. Biol. Chem.295(36), 12814–12821 (2020).
  • BarnesCO , JetteCA , AbernathyMEet al.SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature588(7839), 682–687 (2020).
  • JuB , ZhangQ , GeJet al.Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature584(7819), 115–119 (2020).
  • RogersTF , ZhaoF , HuangDet al.Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science369(6506), 956–963 (2020).
  • MccallumM , DeMarco A , LemppFAet al.N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell184(9), 2332–2347e2316 (2021).
  • SuryadevaraN , ShrihariS , GilchukPet al.Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 Spike protein. Cell184(9), 2316–2331e2315 (2021).
  • CuiZ , LiuP , WangNet al.Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron. Cell185(5), 860–871e813 (2022).
  • ZhangC , WangY , ZhuYet al.Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections. Nat Commun12(1), 264 (2021).
  • WangP , CasnerRG , NairMSet al.A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses. Emerg Microbes Infect11(1), 147–157 (2022).
  • SauerMM , TortoriciMA , ParkYJet al.Structural basis for broad coronavirus neutralization. Nat Struct Mol Biol28(6), 478–486 (2021).
  • ZhouP , YuanM , SongGet al.A human antibody reveals a conserved site on beta-coronavirus Spike proteins and confers protection against SARS-CoV-2 infection. bioRxiv doi:10.1101/2021.03.30.437769 (2022).
  • YangL , LiuW , YuX , WuM , ReichertJM , HoM. COVID-19 antibody therapeutics tracker: a global online database of antibody therapeutics for the prevention and treatment of COVID-19. Antib Ther3(3), 205–212 (2020).
  • HoffmannM , AroraP , GrossRet al.SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies. Cell184(9), 2384–2393e2312 (2021).
  • TadaT , DcostaBM , ZhouH , VaillA , KazmierskiW , LandauNR. Decreased neutralization of SARS-CoV-2 global variants by therapeutic anti-Spike protein monoclonal antibodies. bioRxiv doi:10.1101/2021.02.18.431897 (2021).
  • YueS , LiZ , LinYet al.Sensitivity of SARS-CoV-2 Variants to Neutralization by Convalescent Sera and a VH3-30 Monoclonal Antibody. Front Immunol12, 751584 (2021).
  • LiQ , WuJ , NieJet al.The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity. Cell182(5), 1284–1294e1289 (2020).
  • LiW , ChenY , PrevostJet al.Structural basis and mode of action for two broadly neutralizing antibodies against SARS-CoV-2 emerging variants of concern. Cell Rep38(2), 110210 (2022).
  • HuangKA , ZhouD , TanTKet al.Structures and therapeutic potential of anti-RBD human monoclonal antibodies against SARS-CoV-2. Theranostics12(1), 1–17 (2022).
  • TzouPL , TaoK , PondSLK , ShaferRW. Coronavirus Resistance Database (CoV-RDB): SARS-CoV-2 susceptibility to monoclonal antibodies, convalescent plasma, and plasma from vaccinated persons. PLOS One17(3), e0261045 (2022).
  • HansenJ , BaumA , PascalKEet al.Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science369(6506), 1010–1014 (2020).
  • AbdicheYN , MalashockDS , PinkertonA , PonsJ. Exploring blocking assays using Octet, ProteOn, and Biacore biosensors. Anal. Biochem.386(2), 172–180 (2009).
  • BrooksBD , ClosmoreA , YangJet al.Characterizing Epitope Binding Regions of Entire Antibody Panels by Combining Experimental and Computational Analysis of Antibody: Antigen Binding Competition. Molecules25(16), 3659 (2020).
  • WangY-T , AllenRD , KimKet al.SARS-CoV-2 monoclonal antibodies with therapeutic potential: broad neutralizing activity and No evidence of antibody-dependent enhancement. Antiviral Res.195, 105185 (2021).
  • RosenthalPJ. The Importance of Diagnostic Testing during a Viral Pandemic: Early Lessons from Novel Coronavirus Disease (COVID-19). Am. J. Trop. Med. Hyg.102(5), 915–916 (2020).
  • VandenbergO , MartinyD , RochasO , Van BelkumA , KozlakidisZ. Considerations for diagnostic COVID-19 tests. Nat Rev Microbiol19(3), 171–183 (2021).
  • YamaokaY , MiyakawaK , JeremiahSSet al.Highly specific monoclonal antibodies and epitope identification against SARS-CoV-2 nucleocapsid protein for antigen detection tests. Cell Rep Med2(6), 100311 (2021).
  • PandaPK , ArulMN , PatelPet al.Structure-based drug designing and immunoinformatics approach for SARS-CoV-2. Sci Adv6(28), eabb8097 (2020).
  • XiangF , WangX , HeXet al.Antibody Detection and Dynamic Characteristics in Patients With Coronavirus Disease 2019. Clin. Infect. Dis.71(8), 1930–1934 (2020).
  • BurbeloPD , RiedoFX , MorishimaCet al.Sensitivity in Detection of Antibodies to Nucleocapsid and Spike Proteins of Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Coronavirus Disease 2019. J. Infect. Dis.222(2), 206–213 (2020).
  • TianX , MoC , ZhouLet al.Epitope mapping of severe acute respiratory syndrome-related coronavirus nucleocapsid protein with a rabbit monoclonal antibody. Virus Res.300, 198445 (2021).
  • TianY , ZhangG , LiuHet al.Screening and identification of B cell epitope of the nucleocapsid protein in SARS-CoV-2 using the monoclonal antibodies. Appl. Microbiol. Biotechnol.106(3), 1151–1164 (2022).
  • LeeJ-H , JungY , LeeS-Ket al.Rapid Biosensor of SARS-CoV-2 Using Specific Monoclonal Antibodies Recognizing Conserved Nucleocapsid Protein Epitopes. Viruses14(2), 255 (2022).
  • NielsenM , LundegaardC , WorningPet al.Improved prediction of MHC class I and class II epitopes using a novel Gibbs sampling approach. Bioinformatics. 20(9), 1388–1397 (2004).
  • Sanchez-TrincadoJL , Gomez-PerosanzM , RechePA. Fundamentals and Methods for T- and B-Cell Epitope Prediction. J Immunol. Res. 2017, 2680160 (2017).
  • BianH , HammerJ. Discovery of promiscuous HLA-II-restricted T cell epitopes with TEPITOPE. Methods (San Diego, Calif.). 34(4), 468–475 (2004).
  • GuanP , DoytchinovaIA , ZygouriC , FlowerDR. MHCPred: a server for quantitative prediction of peptide–MHC binding. Nucleic Acids Res. 31(13), 3621–3624 (2003).
  • PetersB , TongW , SidneyJ , SetteA , WengZ. Examining the independent binding assumption for binding of peptide epitopes to MHC-I molecules. Bioinformatics. 19(14), 1765–1772 (2003).
  • LemanJK , MuellerR , KarakasM , WoetzelN , MeilerJ. Simultaneous prediction of protein secondary structure and transmembrane spans. Proteins. 81(7), 1127–1140 (2013).
  • SchmitzAJ , TurnerJS , LiuZet al.Avaccine-induced public antibody protects against SARS-CoV-2 and emerging variants. Immunity. 54(9), 2159–2166; e2156 (2021).