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The \ locations of the RBD and NTD in th:2561)/F 4/H/N/Rect[271.907 464.706 281.095 452.16]/Subtype/Link/Type/Annot>> endobj 4 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 15. Liu, C. et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine an\ d convalescent serum. Cell 184, 4220 4236.e4213 \(2021\).\r:2562)/F 4/H/N/Rect[284.313 464.706 289.518 452.16]/Subtype/Link/Type/Annot>> endobj 5 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 16. Lucas, C. et al. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-ind\ uced immunity. Nature 600, 523 529 \(2021\).\r:2563)/F 4/H/N/Rect[178.631 443.706 183.836 431.16]/Subtype/Link/Type/Annot>> endobj 6 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 17. Greaney, A. J. et al. Mapping mutations to the SARS-CoV-2 RBD that escape bind\ ing by different classes of antibodies. Nat. 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Kamar, N. et al. Three doses of an mRNA COVID-19 vaccine in solid-organ transp\ lant recipients. N. Engl. J. Med. 385, 661 662 \(2021\).\r:2603)/F 4/H/N/Rect[404.048 695.706 409.253 683.16]/Subtype/Link/Type/Annot>> endobj 418 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 44. Hall, V. G. et al. Randomized trial of a third dose of mRNA-1273 vaccine in tr\ ansplant recipients. N. Engl. J. Med. 385, 1244 1246 \(2021\).\r:2604)/F 4/H/N/Rect[410.489 695.706 415.694 683.16]/Subtype/Link/Type/Annot>> endobj 419 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 45. Falsey, A. R. et al. SARS-CoV-2 neutralization with BNT162b2 vaccine dose 3. \ N. Engl. J. Med. 385, 1627 1629 \(2021\).\r:2605)/F 4/H/N/Rect[430.142 653.706 435.347 641.16]/Subtype/Link/Type/Annot>> endobj 420 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 46. Nemet, I. et al. Third BNT162b2 vaccination neutralization of SARS-CoV-2 Omic\ ron infection. N. Engl. J. 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SARS-CoV-2 spike protein: a key target for eliciting persist\ ent neutralizing antibodies. Signal Transduct. Target. Ther. 6, \n95 \(2021\).\r:2611)/F 4/H/N/Rect[342.741 496.206 347.946 483.66]/Subtype/Link/Type/Annot>> endobj 426 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 52. Lan, J. et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound\ to the ACE2 receptor. Nature 581, 215 220 \(2020\).\r:2612)/F 4/H/N/Rect[349.182 496.206 354.387 483.66]/Subtype/Link/Type/Annot>> endobj 427 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 53. Martinez, D. R. et al. Chimeric spike mRNA vaccines protect against Sarbecovir\ us challenge in mice. Science 373, 991 998 \(2021\).\r:2613)/F 4/H/N/Rect[505.985 464.706 511.19 452.16]/Subtype/Link/Type/Annot>> endobj 428 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 54. Xiao, Y. et al. Emerging mRNA technologies: Delivery strategies and biomedical\ applications. Chem. Soc. 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Cell 184, 4203 4219.e4232 \(2021\).\r:2624)/F 4/H/N/Rect[355.27 128.706 360.475 116.16]/Subtype/Link/Type/Annot>> endobj 439 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd:Fig. 2 | Targeting the S protein of the variants with NP-based vaccine-elicited neu\ tralizing antibodies. a, Original NP-based mRNA vaccine and its derivatives, including the variant-modified mRNA vaccine, \ the chimeric spike mRNA vaccine an:2600)/F 4/H/N/Rect[237.504 212.706 246.051 200.16]/Subtype/Link/Type/Annot>> endobj 440 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd:Fig. 2 | Targeting the S protein of the variants with NP-based vaccine-elicited ne\ utralizing antibodies. a, Original NP-based mRNA vaccine and its derivatives, including the variant-modified mRNA vaccine,\ the chimeric spike mRNA vaccine a:2601)/F 4/H/N/Rect[216.872 160.206 226.06 147.66]/Subtype/Link/Type/Annot>> endobj 441 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 42. Teijaro, J. R. & Farber, D. L. COVID-19 vaccines: modes of immune activation a\ nd future challenges. Nat. Rev. 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Aves, K.-L., Goksyr, L. & Sander, A. F. Advantages and prospects of Tag/Catc\ her mediated antigen display on capsid-like particle-based vaccines. Viruses 12, 185 \(2020\).\r:2633)/F 4/H/N/Rect[399.844 685.206 405.049 672.66]/Subtype/Link/Type/Annot>> endobj 481 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 68. Muyldermans, S. Nanobodies: natural single-domain antibodies. Annu. Rev. Bioc\ hem. 82, 775 797 \(2013\).\r:2634)/F 4/H/N/Rect[342.287 517.206 347.492 504.66]/Subtype/Link/Type/Annot>> endobj 482 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 69. Vanlandschoot, P. et al. Nanobodies: new ammunition to battle viruses. Ant\ iviral Res. 92, 389 407 \(2011\).\r:2635)/F 4/H/N/Rect[357.069 464.706 362.274 452.16]/Subtype/Link/Type/Annot>> endobj 483 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 70. Detalle, L. et al. 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Nature 595, 278 282 \(2021\).\r:2642)/F 4/H/N/Rect[448.245 265.206 453.45 252.66]/Subtype/Link/Type/Annot>> endobj 490 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd:Fig. 3 | Targeting the S protein of variants with engineered neutralizing antibod\ ies and ACE2-based nanodecoys. a, Engineered neutralizing antibodies: a single nanobody, a nanobody hexamer containing an \ IgG Fc, a nanobody dimer consistin:2643)/F 4/H/N/Rect[527.225 181.206 535.772 168.66]/Subtype/Link/Type/Annot>> endobj 491 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 75. Koenig, P.-A. et al. Structure-guided multivalent nanobodies block SARS-CoV-2 \ infection and suppress mutational escape. Science 371, eabe6230 \(2021\).\r:2644)/F 4/H/N/Rect[538.989 181.206 544.194 168.66]/Subtype/Link/Type/Annot>> endobj 492 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 76. Saelens, X. & Schepens, B. Single-domain antibodies make a difference. Scienc\ e 371, 681 682 \(2021\).\r:2645)/F 4/H/N/Rect[545.431 181.206 550.636 168.66]/Subtype/Link/Type/Annot>> endobj 493 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd:Fig. 2 | Targeting the S protein of the variants with NP-based vaccine-elicit\ ed neutralizing antibodies. a, Original NP-based mRNA vaccine and its derivatives, including the variant-modified mRNA vac\ cine, the chimeric spike mRNA vacc:2625)/F 4/H/N/Rect[266.256 212.706 274.654 200.16]/Subtype/Link/Type/Annot>> endobj 494 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 61. Walls, A. C. et al. Elicitation of broadly protective sarbecovirus immunity by\ receptor-binding domain nanoparticle vaccines. Cell 184, 5432 5447 \(2021\).\r:2626)/F 4/H/N/Rect[277.872 212.706 283.077 200.16]/Subtype/Link/Type/Annot>> endobj 495 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 62. Walls, A. C. et al. Elicitation of potent neutralizing antibody responses by d\ esigned protein nanoparticle vaccines for SARS-CoV-2. Cell 183, 1367 1382.e1317 \(2020\).\r:2627)/F 4/H/N/Rect[284.313 212.706 289.518 200.16]/Subtype/Link/Type/Annot>> endobj 496 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 63. He, L. et al. Single-component, self-assembling, protein nanoparticles present\ ing the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates. Sci. Adv. 7, eabf1591 \(2021\).\r:262\ 8)/F 4/H/N/Rect[284.313 160.206 289.518 147.66]/Subtype/Link/Type/Annot>> endobj 497 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 63. He, L. et al. Single-component, self-assembling, protein nanoparticles presen\ ting the receptor binding domain and stabilized spike as SARS-CoV-2 vaccine candidates. Sci. Adv. 7, eabf1591 \(2021\).\r:26\ 29)/F 4/H/N/Rect[155.207 107.706 160.412 95.1602]/Subtype/Link/Type/Annot>> endobj 498 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 64. Zhang, Y.-N. et al. Mechanism of a COVID-19 nanoparticle vaccine candidate tha\ t elicits a broadly neutralizing antibody response to SARS-CoV-2 variants. Sci. Adv. 7, eabj3107 \(2021\).\r:2630)/F 4/H/N/Rect[161.649 107.706 166.854 95.1602]/Subtype/Link/Type/Annot>> endobj 499 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 65. Aves, K.-L., Goksyr, L. & Sander, A. F. Advantages and prospects of Tag/Catch\ er mediated antigen display on capsid-like particle-based vaccines. Viruses 12, 185 \(2020\).\r:2631)/F 4/H/N/Rect[224.289 55.2059 229.494 42.6602]/Subtype/Link/Type/Annot>> endobj 500 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 67. Brune, K. D. & Howarth, M. New routes and opportunities for modular constructi\ on of particulate vaccines: stick, click, and glue. Front. Immunol. 9, 1432 \(2018\).\r:2632)/F 4/H/N/Rect[232.313 55.2059 237.518 42.6602]/Subtype/Link/Type/Annot>> endobj 501 0 obj <>/BS<>/Border[0 0 0]/F 4/H/N/Rect[438.936 33.864 552.756 25.1497]/Subtype/Link/Type/Annot>> endobj 502 0 obj <>/ExtGState<>/Font<>/ProcSet[/PDF/Text/ImageC/ImageI]/Properties<>/XObject<>>> endobj 503 0 obj <>stream xَeɕ%ߠ>FHy.mF, ԠD)'ӻ2""2bϕd{-ιv=ovCr~}ڧ}Z/:W˫/~U~+uoN^mg?gʞ&'NѤWI˻?od՛-u>kצ?ބo߸wN?{Yx&6?Oo}}#?~~wϧ?)&._6>^mkߟPzNXI7^߿z|؝ef뿼?Bx";uY|důE.޿?߷EDlMv4䄭mwVߔǶ%7yל>E>p,)"qRuM$'~HYY#*Kpw?!]|ʦdiߗ'U'']??|}G/ostWJ|ק|I>9U2m<"r,;37vqp>s[2?j?cO[<;Yt= Y3cnI[{eK>@S;:xw:98?\y+?my[|Dq(y_vS}AtܘgE>?Ǔhw\rISI{:;mdyt-ǿl.9U YŨRt_O߼*V֧?)J];}]R9a_W!:|?k*tWG~N6nAyOw[nZ>ɹ&OgS~/MT} ,{aUNkQ<|d-koD~<}B]. 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Med. 386, 492 494 \(2021\). \nThis study shows that a third dose does elicit Omicron neutraliz\ ing antibodies shortly after adminis:2714)/F 4/H/N/Rect[420.501 191.706 425.608 179.16]/Subtype/Link/Type/Annot>> endobj 598 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 47. Pajon, R. et al. SARS-CoV-2 Omicron variant neutralization after mRNA-1273 bo\ oster vaccination. N. Engl. J. Med. 386, 1088 1091 \(2022\).\r:2715)/F 4/H/N/Rect[426.796 191.706 431.903 179.16]/Subtype/Link/Type/Annot>> endobj 599 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 29. Cameroni, E. et al. Broadly neutralizing antibodies overcome SARS-CoV-2 Omic\ ron antigenic shift. Nature 602, 664 670 \(2022\).\r:2716)/F 4/H/N/Rect[454.53 170.706 459.638 158.16]/Subtype/Link/Type/Annot>> endobj 600 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 130. Pulliam, J. R. C. et al. Increased risk of SARS-CoV-2 reinfection \nassociate\ d with emergence of Omicron in South Africa. Science 376, eabn4947 \(2022\).\r:2717)/F 4/H/N/Rect[460.825 170.706 468.486 158.16]/Subtype/Link/Type/Annot>> endobj 601 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 131. Moderna announces preliminary booster data and updates strategy to address Omicr\ on variant. Business Wire https://www.businesswire.com/\nnews/home/20211220005253/en/Moderna-Announces-Preliminary-Booster-\n\ Data-and-Updates-Strategy-to-Addres:2718)/F 4/H/N/Rect[453.576 149.706 461.237 137.16]/Subtype/Link/Type/Annot>> endobj 602 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 132. Pfizer and BioNTech provide update on Omicron variant. 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S. et al. Designer DNA architecture offers precise and multivalent s\ patial pattern-recognition for viral sensing and inhibition. Nat. Chem. 12, 26 35 \(2020\).\r:2685)/F 4/H/N/Rect[170.818 370.206 178.625 357.66]/Subtype/Link/Type/Annot>> endobj 612 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 108. Sigl, C. et al. Programmable icosahedral shell system for virus trapping. Na\ t. Mater. 20, 1281 1289 \(2021\). \nThis study demonstrates the possibility of using DNA architecture to capture virus.\r:\ 2686)/F 4/H/N/Rect[179.861 370.206 187.669 357.66]/Subtype/Link/Type/Annot>> endobj 613 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 109. Sacc, B. & Niemeyer, C. M. DNA origami: the art of folding DNA. Angew. Chem\ . Int. Ed. 51, 58 66 \(2012\).\r:2687)/F 4/H/N/Rect[137.427 349.206 145.235 336.66]/Subtype/Link/Type/Annot>> endobj 614 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 108. Sigl, C. et al. Programmable icosahedral shell system for virus trapping. N\ at. Mater. 20, 1281 1289 \(2021\). \nThis study demonstrates the possibility of using DNA architecture to capture virus.\r\ :2688)/F 4/H/N/Rect[281.71 307.206 289.518 294.66]/Subtype/Link/Type/Annot>> endobj 615 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 103. Peplow, M. Nanotechnology offers alternative ways to fight COVID-19 pandemic \ with antivirals. Nat. 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Structures of SARS-CoV-2 B.1.351 neutralizing antibodies provid\ e insights into cocktail design against concerning variants. Cell Res. 31, 1130 1133 \(2021\).\r:2692)/F 4/H/N/Rect[72.0095 97.2059 79.8169 84.6602]/Subtype/Link/Type/Annot>> endobj 619 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 112. Wang, L. et al. Ultrapotent antibodies against diverse and highly transmissib\ le SARS-CoV-2 variants. Science 373, eabh1766 \(2021\).\r:2693)/F 4/H/N/Rect[81.0531 97.2059 88.8605 84.6602]/Subtype/Link/Type/Annot>> endobj 620 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatNano_1174.indd: 113. Dussupt, V. et al. Low-dose in vivo protection and neutralization across SARS\ -CoV-2 variants by monoclonal antibody combinations. Nat. 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