Single-domain antibodies targeting neuraminidase protect against an H5N1 influenza virus challenge

Journal of Virology

Volumn 88, Issue 15, 2014, Pages 8278-8296

  Cardoso, Francisco Miguel ^a,b   Ibañez, Lorena Itatí ^a,b,e   Hoecke, Silvie Van den ^a,b   Baets, Sarah De ^a,b   Smet, Anouk ^a,b   Roose, Kenny ^a,b   Schepens, Bert ^a,b   Descamps, Francis J ^a,b,f   Fiers, Walter ^a,b   Muyldermans, Serge ^a,d   Depicker, Ann ^a,c   Saelens, Xavier ^a,b  

^a DEPARTMENT OF PLANT SYSTEMS BIOLOGY   (Belgium)

^b GHENT UNIVERSITY   (Belgium)

^c Structural Biology Research Center VIB ^*  (Belgium)

^d VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

^e Facultad de Ciencias Naturales e Instituto M Lillo   (Argentina)

^f ABLYNX NV   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

INFLUENZA VIRUS NEURAMINIDASE SPECIFIC SINGLE DOMAIN ANTIBODY; OSELTAMIVIR; UNCLASSIFIED DRUG; VIRUS SIALIDASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBIOTIC RESISTANCE; ANTIVIRAL ACTIVITY; ARTICLE; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DRUG TARGETING; ENZYME ACTIVE SITE; ENZYME ACTIVITY; GENE FUSION; IN VITRO STUDY; IN VIVO STUDY; INFLUENZA A (H5N1); INFLUENZA VIRUS A H5N1; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FUNCTION; VIRUS ISOLATION; VIRUS LOAD; VIRUS NEUTRALIZATION; VIRUS REPLICATION; VIRUS STRAIN;

ANIMALS; ANTIVIRAL AGENTS; DISEASE MODELS, ANIMAL; FEMALE; INFLUENZA A VIRUS, H5N1 SUBTYPE; INHIBITORY CONCENTRATION 50; MICE; MICE, INBRED BALB C; MICROBIAL SENSITIVITY TESTS; NEURAMINIDASE; ORTHOMYXOVIRIDAE INFECTIONS; SINGLE-DOMAIN ANTIBODIES; TREATMENT OUTCOME;

EID: 84903890727     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.03178-13     Document Type: Article

References (85)

1. Herfst S, Schrauwen EJ, Linster M, Chutinimitkul S, de Wit E, Munster VJ, Sorrell EM, Bestebroer TM, Burke DF, Smith DJ, Rimmelzwaan GF, Osterhaus AD, Fouchier RA. 2012. Airborne transmission of influenza A/H5N1 virus between ferrets. Science 336:1534-1541. http://dx.doi.org/10.1126/science.1213362.
2. Imai M, Watanabe T, Hatta M, Das SC, Ozawa M, Shinya K, Zhong G, Hanson A, Katsura H, Watanabe S, Li C, Kawakami E, Yamada S, Kiso M, Suzuki Y, Maher EA, Neumann G, Kawaoka Y. 2012. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 486:420-428. http://dx.doi.org/10.1038/nature10831.
3. Tran TH, Nguyen TL, Nguyen TD, Luong TS, Pham PM, VNguyen v, Pham TS, Vo CD, Le TQ, Ngo TT, Dao BK, Le PP, Nguyen TT, Hoang TL, Cao VT, Le TG, Nguyen DT, Le HN, Nguyen KT, Le HS, Le VT, Christiane D, Tran TT, de Jong M, Schultsz C, Cheng P, Lim W, Horby P, Farrar J, World Health Organization International Avian Influenza Investigative Team. 2004. Avian influenza A (H5N1) in 10 patients in Vietnam. N. Engl. J. Med. 350:1179-1188. http://dx.doi.org/10.1056/NEJMoa040419.
4. Trifonov V, Khiabanian H, Rabadan R. 2009. Geographic dependence, surveillance, and origins of the 2009 influenza A (H1N1) virus. N. Engl. J. Med. 361:115-119. http://dx.doi.org/10.1056/NEJMp0904572.
5. Gao HN, Lu HZ, Cao B, Du B, Shang H, Gan JH, Lu SH, Yang YD, Fang Q, Shen YZ, Xi XM, Gu Q, Zhou XM, Qu HP, Yan Z, Li FM, Zhao W, Gao ZC, Wang GF, Ruan LX, Wang WH, Ye J, Cao HF, Li XW, Zhang WH, Fang XC, He J, Liang WF, Xie J, Zeng M, Wu XZ, Li J, Xia Q, Jin ZC, Chen Q, Tang C, Zhang ZY, Hou BM, Feng ZX, Sheng JF, Zhong NS, Li LJ. 2013. Clinical findings in 111 cases of influenza A (H7N9) virus infection. N. Engl. J. Med. 368:2277-2285. http://dx.doi.org/10.1056/NEJMoa1305584.
6. Roose K, Fiers W, Saelens X. 2009. Pandemic preparedness: toward a universal influenza vaccine. Drug News Perspect. 22:80-92. http://dx.doi.org/10.1358/dnp.2009.22.2.1334451.
7. de Jong MD, Simmons CP, Thanh TT, Hien VM, Smith GJ, Chau TN, Hoang DM, Chau NVV, Khanh TH, Dong VC, Qui PT, Cam BV, Ha DQ, Guan Y, Peiris JS, Chinh NT, Hien TT, Farrar J. 2006. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat. Med. 12:1203-1207. http://dx.doi.org/10.1038/nm1477.
8. Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk HD. 2004. Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. J. Virol. 78:12665-12667. http://dx.doi.org/10.1128/JVI.78.22.12665-12667.2004.
9. Johansson BE, Matthews JT, Kilbourne ED. 1998. Supplementation of conventional influenza A vaccine with purified viral neuraminidase results in a balanced and broadened immune response. Vaccine 16:1009-1015. http://dx.doi.org/10.1016/S0264-410X(97)00279-X.
10. Kilbourne ED, Pokorny BA, Johansson B, Brett I, Milev Y, Matthews JT. 2004. Protection of mice with recombinant influenza virus neuraminidase. J. Infect. Dis. 189:459-461. http://dx.doi.org/10.1086/381123.
11. Marcelin G, Sandbulte MR, Webby RJ. 2012. Contribution of antibody production against neuraminidase to the protection afforded by influenza vaccines. Rev. Med. Virol. 22:267-279. http://dx.doi.org/10.1002/rmv.1713.
12. Goto H, Kawaoka Y. 1998. A novel mechanism for the acquisition of virulence by a human influenza A virus. Proc. Natl. Acad. Sci. U.S.A. 95:10224-10228. http://dx.doi.org/10.1073/pnas.95.17.10224.
13. Li S, Schulman J, Itamura S, Palese P. 1993. Glycosylation of neuraminidase determines the neurovirulence of influenza A/WSN/33 virus. J. Virol. 67:6667-6673.
14. Matsuoka Y, Swayne DE, Thomas C, Rameix-Welti MA, Naffakh N, Warnes C, Altholtz M, Donis R, Subbarao K. 2009. Neuraminidase stalk length and additional glycosylation of the hemagglutinin influence the virulence of influenza H5N1 viruses for mice. J. Virol. 83:4704-4708. http://dx.doi.org/10.1128/JVI.01987-08.
15. Huang IC, Li W, Sui J, Marasco W, Choe H, Farzan M. 2008. Influenza A virus neuraminidase limits viral superinfection. J. Virol. 82:4834-4843. http://dx.doi.org/10.1128/JVI.00079-08.
16. Ilyushina NA, Bovin NV, Webster RG. 2012. Decreased neuraminidase activity is important for the adaptation of H5N1 influenza virus to human airway epithelium. J. Virol. 86:4724-4733. http://dx.doi.org/10.1128/JVI.06774-11.
17. Takahashi Y, Hasegawa H, Hara Y, Ato M, Ninomiya A, Takagi H, Odagiri T, Sata T, Tashiro M, Kobayashi K. 2009. Protective immunity afforded by inactivated H5N1 (NIBRG-14) vaccine requires antibodies against both hemagglutinin and neuraminidase in mice. J. Infect. Dis. 199:1629-1637. http://dx.doi.org/10.1086/598954.
18. Gubareva LV, Nedyalkova MS, Novikov DV, Murti KG, Hoffmann E, Hayden FG. 2002. A release-competent influenza A virus mutant lacking the coding capacity for the neuraminidase active site. J. Gen. Virol. 83: 2683-2692.
19. Mitnaul LJ, Matrosovich MN, Castrucci MR, Tuzikov AB, Bovin NV, Kobasa D, Kawaoka Y. 2000. Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A virus. J. Virol. 74:6015-6020. http://dx.doi.org/10.1128/JVI.74.13.6015-6020.2000.
20. Nedyalkova MS, Hayden FG, Webster RG, Gubareva LV. 2002. Accumulation of defective neuraminidase (NA) genes by influenza A viruses in the presence of NA inhibitors as a marker of reduced dependence on NA. J. Infect. Dis. 185:591-598. http://dx.doi.org/10.1086/339358.
21. Murphy BR, Kasel JA, Chanock RM. 1972. Association of serum antineuraminidase antibody with resistance to influenza in man. N. Engl. J. Med. 286:1329-1332. http://dx.doi.org/10.1056/NEJM197206222862502.
22. Vanlandschoot P, Stortelers C, Beirnaert E, Ibañez LI, Schepens B, Depla E, Saelens X. 2011. Nanobodies®: new ammunition to battle viruses. Antiviral Res. 92:389-407. http://dx.doi.org/10.1016/j.antiviral.2011.09.002.
23. Greenberg AS, Avila D, Hughes M, Hughes A, McKinney EC, Flajnik MF. 1995. A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks. Nature 374:168-173. http://dx.doi.org/10.1038/374168a0.
24. Hamers-Casterman C, Atarhouch T, Muyldermans S, Robinson G, Hamers C, Songa EB, Bendahman N, Hamers R. 1993. Naturally occurring antibodies devoid of light chains. Nature 363:446-448. http://dx.doi.org/10.1038/363446a0.
25. Coppieters K, Dreier T, Silence K, de Haard H, Lauwereys M, Casteels P, Beirnaert E, Jonckheere H, Van de Wiele C, Staelens L, Hostens J, Revets H, Remaut E, Elewaut D, Rottiers P. 2006. Formatted anti-tumor necrosis factor alpha VHH proteins derived from camelids show superior potency and targeting to inflamed joints in a murine model of collageninduced arthritis. Arthritis Rheum. 54:1856-1866. http://dx.doi.org/10.1002/art.21827.
26. Saerens D, Ghassabeh GH, Muyldermans S. 2008. Single-domain antibodies as building blocks for novel therapeutics. Curr. Opin. Pharmacol. 8:600-608. http://dx.doi.org/10.1016/j.coph.2008.07.006.
27. Decanniere K, Desmyter A, Lauwereys M, Ghahroudi MA, Muyldermans S, Wyns L. 1999. A single-domain antibody fragment in complex with RNase A: non-canonical loop structures and nanomolar affinity using twoCDRloops. Structure 7:361-370. http://dx.doi.org/10.1016/S0969-2126(99)80049-5.
28. Decanniere K, Muyldermans S, Wyns L. 2000. Canonical antigenbinding loop structures in immunoglobulins: more structures, more canonical classes? J. Mol. Biol. 300:83-91. http://dx.doi.org/10.1006/jmbi.2000.3839.
29. Ward ES, Gussow D, Griffiths AD, Jones PT, Winter G. 1989. Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli. Nature 341:544-546. http://dx.doi.org/10.1038/341544a0.
30. Desmyter A, Spinelli S, Payan F, Lauwereys M, Wyns L, Muyldermans S, Cambillau C. 2002. Three camelid VHH domains in complex with porcine pancreatic alpha-amylase. Inhibition and versatility of binding topology. J. Biol. Chem. 277:23645-23650. http://dx.doi.org/10.1074/jbc.M202327200.
31. Lauwereys M, Arbabi Ghahroudi M, Desmyter A, Kinne J, Holzer W, De Genst E, Wyns L, Muyldermans S. 1998. Potent enzyme inhibitors derived from dromedary heavy-chain antibodies. EMBO J. 17:3512-3520. http://dx.doi.org/10.1093/emboj/17.13.3512.
32. Rasmussen SG, Choi HJ, Fung JJ, Pardon E, Casarosa P, Chae PS, Devree BT, Rosenbaum DM, Thian FS, Kobilka TS, Schnapp A, Konetzki I, Sunahara RK, Gellman SH, Pautsch A, Steyaert J, Weis WI, Kobilka BK. 2011. Structure of a nanobody-stabilized active state of the beta(2) adrenoceptor. Nature 469:175-180. http://dx.doi.org/10.1038/nature09648.
33. De Genst E, Silence K, Decanniere K, Conrath K, Loris R, Kinne J, Muyldermans S, Wyns L. 2006. Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies. Proc. Natl. Acad. Sci. U.S.A. 103:4586-4591. http://dx.doi.org/10.1073/pnas.0505379103.
34. Hultberg A, Temperton NJ, Rosseels V, Koenders M, Gonzalez-Pajuelo M, Schepens B, Ibañez LI, Vanlandschoot P, Schillemans J, Saunders M, Weiss RA, Saelens X, Melero JA, Verrips CT, Van Gucht S, de Haard HJ. 2011. Llama-derived single domain antibodies to build multivalent, superpotent and broadened neutralizing anti-viral molecules. PLoS One 6:e17665. http://dx.doi.org/10.1371/journal.pone.0017665.
35. Ibañez LI, De Filette M, Hultberg A, Verrips T, Temperton N, Weiss RA, Vandevelde W, Schepens B, Vanlandschoot P, Saelens X. 2011. Nanobodies with in vitro neutralizing activity protect mice against H5N1 influenza virus infection. J. Infect. Dis. 203:1063-1072. http://dx.doi.org/10.1093/infdis/jiq168.
36. Schepens B, Ibañez LI, De Baets S, Hultberg A, Bogaert P, De Bleser P, Vervalle F, Verrips T, Melero J, Vandevelde W, Vanlandschoot P, Saelens X. 2011. Nanobodies® specific for respiratory syncytial virus fusion protein protect against infection by inhibition of fusion. J. Infect. Dis. 204:1692-1701. http://dx.doi.org/10.1093/infdis/jir622.
37. Tillib SV, Ivanova TI, Vasilev LA, Rutovskaya MV, Saakyan SA, Gribova IY, Tutykhina IL, Sedova ES, Lysenko AA, Shmarov MM, Logunov DY, Naroditsky BS, Gintsburg AL. 2013. Formatted singledomain antibodies can protect mice against infection with influenza virus (H5N2). Antiviral Res. 97:245-254. http://dx.doi.org/10.1016/j.antiviral.2012.12.014.
38. Wei G, Meng W, Guo H, Pan W, Liu J, Peng T, Chen L, Chen CY. 2011. Potent neutralization of influenza A virus by a single-domain antibody blocking M2 ion channel protein. PLoS One 6:e28309. http://dx.doi.org/10.1371/journal.pone.0028309.
39. Harmsen M, Pritz-Verschuren BJS, Bartenlink W, Van der Burg H, Koch G. 2013. Isolation of panels of llama single-domain antibody fragments binding all nine neuraminidase subtypes of influenza A virus. Antibodies 2:168-192. http://dx.doi.org/10.3390/antib2020168.
40. Van Borm S, Thomas I, Hanquet G, Lambrecht B, Boschmans M, Dupont G, Decaestecker M, Snacken R, van den Berg T. 2005. Highly pathogenic H5N1 influenza virus in smuggled Thai eagles, Belgium. Emerg. Infect. Dis. 11:702-705. http://dx.doi.org/10.3201/eid1105.050211.
41. Hoffmann E, Krauss S, Perez D, Webby R, Webster RG. 2002. Eightplasmid system for rapid generation of influenza virus vaccines. Vaccine 20:3165-3170. http://dx.doi.org/10.1016/S0264-410X(02)00268-2.
42. Schotsaert M, Ysenbaert T, Neyt K, Ibañez LI, Bogaert P, Schepens B, Lambrecht BN, Fiers W, Saelens X. 2013. Natural and long-lasting cellular immune responses against influenza in the M2e-immune host. Mucosal Immunol. 6:276-287. http://dx.doi.org/10.1038/mi.2012.69.
43. Reed LJ, Muench H. 1938. A simple method for estimating fifty percent endpoints. Am. J. Hyg. 27:493-497.
44. De Filette M, Martens W, Roose K, Deroo T, Vervalle F, Bentahir M, Vandekerckhove J, Fiers W, Saelens X. 2008. An influenza A vaccine based on tetrameric ectodomain of matrix protein 2. J. Biol. Chem. 283: 11382-11387. http://dx.doi.org/10.1074/jbc.M800650200.
45. Harbury PB, Zhang T, Kim PS, Alber T. 1993. A switch between two-, three-, and four-stranded coiled coils in GCN4 leucine zipper mutants. Science 262:1401-1407. http://dx.doi.org/10.1126/science.8248779.
46. Hassantoufighi A, Zhang H, Sandbulte M, Gao J, Manischewitz J, King L, Golding H, Straight TM, Eichelberger MC. 2010. A practical influenza neutralization assay to simultaneously quantify hemagglutinin and neuraminidase-inhibiting antibody responses. Vaccine 28:790-797. http://dx.doi.org/10.1016/j.vaccine.2009.10.066.
47. Arbabi Ghahroudi M, Desmyter A, Wyns L, Hamers R, Muyldermans S. 1997. Selection and identification of single domain antibody fragments from camel heavy-chain antibodies. FEBS Lett. 414:521-526. http://dx.doi.org/10.1016/S0014-5793(97)01062-4.
48. Kang AS, Jones TM, Burton DR. 1991. Antibody redesign by chain shuffling from random combinatorial immunoglobulin libraries. Proc. Natl. Acad. Sci. U.S.A. 88:11120-11123. http://dx.doi.org/10.1073/pnas.88.24.11120.
49. De Meyer T, Eeckhout D, De Rycke R, De Buck S, Muyldermans S, Depicker A. 2014. Generation of VHH antibodies against the Arabidopsis thaliana seed storage proteins. Plant Mol. Biol. 84:83-93. http://dx.doi.org/10.1007/s11103-013-0118-0.
50. Lambert C, Leonard N, De Bolle X, Depiereux E. 2002. ESyPred3D: prediction of proteins [sic] 3D structures. Bioinformatics 18:1250-1256. http://dx.doi.org/10.1093/bioinformatics/18.9.1250.
51. Els Conrath K, Lauwereys M, Wyns L, Muyldermans S. 2001. Camel single-domain antibodies as modular building units in bispecific and bivalent antibody constructs. J. Biol. Chem. 276:7346-7350. http://dx.doi.org/10.1074/jbc.M007734200.
52. Conrath KE, Lauwereys M, Galleni M, Matagne A, Frere JM, Kinne J, Wyns L, Muyldermans S. 2001. β-Lactamase inhibitors derived from single-domain antibody fragments elicited in the Camelidae. Antimicrob. Agents Chemother. 45:2807-2812. http://dx.doi.org/10.1128/AAC.45.10.2807-2812.2001.
53. Clough SJ, Bent AF. 1998. Floral dip: a simplified method for Agrobacterium-mediated transformation of Arabidopsis thaliana. Plant J. 16:735-743. http://dx.doi.org/10.1046/j.1365-313x.1998.00343.x.
54. De Buck S, Virdi V, De Meyer T, De Wilde K, Piron R, Nolf J, Van Lerberge E, De Paepe A, Depicker A. 2012. Production of camel-like antibodies in plants. Methods Mol. Biol. 911:305-324. http://dx.doi.org/10.1007/978-1-61779-968-6_19.
55. Böttcher E, Freuer C, Steinmetzer T, Klenk HD, Garten W. 2009. MDCK cells that express proteases TMPRSS2 and HAT provide a cell system to propagate influenza viruses in the absence of trypsin and to study cleavage of HA and its inhibition. Vaccine 27:6324-6329. http://dx.doi.org/10.1016/j.vaccine.2009.03.029.
56. Matrosovich M, Matrosovich T, Garten W, Klenk HD. 2006. New low-viscosity overlay medium for viral plaque assays. Virol. J. 3:63. http://dx.doi.org/10.1186/1743-422X-3-63.
57. Stech J, Stech O, Herwig A, Altmeppen H, Hundt J, Gohrbandt S, Kreibich A, Weber S, Klenk HD, Mettenleiter TC. 2008. Rapid and reliable universal cloning of influenza A virus genes by target-primed plasmid amplification. Nucleic Acids Res. 36:e139. http://dx.doi.org/10.1093/nar/gkn646.
58. De Jaeger G, Scheffer S, Jacobs A, Zambre M, Zobell O, Goossens A, Depicker A, Angenon G. 2002. Boosting heterologous protein production in transgenic dicotyledonous seeds using Phaseolus vulgaris regulatory sequences. Nat. Biotechnol. 20:1265-1268. http://dx.doi.org/10.1038/nbt755.
59. Van Droogenbroeck B, Cao J, Stadlmann J, Altmann F, Colanesi S, Hillmer S, Robinson DG, Van Lerberge E, Terryn N, Van Montagu M, Liang M, Depicker A, De Jaeger G. 2007. Aberrant localization and underglycosylation of highly accumulating single-chain Fv-Fc antibodies in transgenic Arabidopsis seeds. Proc. Natl. Acad. Sci. U.S.A. 104:1430-1435. http://dx.doi.org/10.1073/pnas.0609997104.
60. WHO/OIE/FAO H5N1 Evolution Working Group. 2012. Continued evolution of highly pathogenic avian influenza A (H5N1): updated nomenclature. Influenza Other Respir. Viruses 6:1-5. http://dx.doi.org/10.1111/j.1750-2659.2011.00298.x.
61. Kandun IN, Wibisono H, Sedyaningsih ER, Yusharmen Hadisoedarsuno W, Purba W, Santoso H, Septiawati C, Tresnaningsih E, Heriyanto B, Yuwono D, Harun S, Soeroso S, Giriputra S, Blair PJ, Jeremijenko A, Kosasih H, Putnam SD, Samaan G, Silitonga M, Chan KH, Poon LL, Lim W, Klimov A, Lindstrom S, Guan Y, Donis R, Katz J, Cox N, Peiris M, Uyeki TM. 2006. Three Indonesian clusters of H5N1 virus infection in 2005. N. Engl. J. Med. 355:2186-2194. http://dx.doi.org/10.1056/NEJMoa060930.
62. Wang MZ, Tai CY, Mendel DB. 2002. Mechanism by which mutations at His274 alter sensitivity of influenza A virus N1 neuraminidase to oseltamivir carboxylate and zanamivir. Antimicrob. Agents Chemother. 46: 3809-3816. http://dx.doi.org/10.1128/AAC.46.12.3809-3816.2002.
63. Brandes M, Klauschen F, Kuchen S, Germain RN. 2013. A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection. Cell 154:197-212. http://dx.doi.org/10.1016/j.cell.2013.06.013.
64. Govorkova EA, Leneva IA, Goloubeva OG, Bush K, Webster RG. 2001. Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses. Antimicrob. Agents Chemother. 45:2723-2732. http://dx.doi.org/10.1128/AAC.45.10.2723-2732.2001.
65. Doyle TM, Jaentschke B, Van Domselaar G, Hashem AM, Farnsworth A, Forbes NE, Li C, Wang J, He R, Brown EG, Li X. 2013. The universal epitope of influenza A viral neuraminidase fundamentally contributes to enzyme activity and viral replication. J. Biol. Chem. 288:18283-18289. http://dx.doi.org/10.1074/jbc.M113.468884.
66. Gravel C, Li C, Wang J, Hashem AM, Jaentschke B, Xu KW, Lorbetskie B, Gingras G, Aubin Y, Van Domselaar G, Girard M, He R, Li X. 2010. Qualitative and quantitative analyses of virtually all subtypes of influenza A and B viral neuraminidases using antibodies targeting the universally conserved sequences. Vaccine 28:5774-5784. http://dx.doi.org/10.1016/j.vaccine.2010.06.075.
67. Wan H, Gao J, Xu K, Chen H, Couzens LK, Rivers KH, Easterbrook JD, Yang K, Zhong L, Rajabi M, Ye J, Sultana I, Wan XF, Liu X, Perez DR, Taubenberger JK, Eichelberger MC. 2013. Molecular basis for broad neuraminidase immunity: conserved epitopes in seasonal and pandemic H1N1 as well as H5N1 influenza viruses. J. Virol. 87:9290-9300. http://dx.doi.org/10.1128/JVI.01203-13.
68. McKimm-Breschkin JL, Blick TJ, Sahasrabudhe A, Tiong T, Marshall D, Hart GJ, Bethell RC, Penn CR. 1996. Generation and characterization of variants of NWS/G70C influenza virus after in vitro passage in 4-amino-Neu5Ac2en and 4-guanidino-Neu5Ac2en. Antimicrob. Agents Chemother. 40:40-46.
69. Johansson BE, Moran TM, Bona CA, Popple SW, Kilbourne ED. 1987. Immunologic response to influenza virus neuraminidase is influenced by prior experience with the associated viral hemagglutinin. II. Sequential infection of mice simulates human experience. J. Immunol. 139:2010-2014.
70. Schulman JL, Khakpour M, Kilbourne ED. 1968. Protective effects of specific immunity to viral neuraminidase on influenza virus infection of mice. J. Virol. 2:778-786.
71. Cate TR, Rayford Y, Nino D, Winokur P, Brady R, Belshe R, Chen W, Atmar RL, Couch RB. 2010. A high dosage influenza vaccine induced significantly more neuraminidase antibody than standard vaccine among elderly subjects. Vaccine 28:2076-2079. http://dx.doi.org/10.1016/j.vaccine.2009.12.041.
72. Air GM. 2012. Influenza neuraminidase. Influenza Other Respir. Viruses 6:245-256. http://dx.doi.org/10.1111/j.1750-2659.2011.00304.x.
73. Hensley SE, Das SR, Gibbs JS, Bailey AL, Schmidt LM, Bennink JR, Yewdell JW. 2011. Influenza A virus hemagglutinin antibody escape promotes neuraminidase antigenic variation and drug resistance. PLoS One 6:e15190. http://dx.doi.org/10.1371/journal.pone.0015190.
74. Shoji Y, Chichester JA, Palmer GA, Farrance CE, Stevens R, Stewart M, Goldschmidt L, Deyde V, Gubareva L, Klimov A, Mett V, Yusibov V. 2011. An influenza N1 neuraminidase-specific monoclonal antibody with broad neuraminidase inhibition activity against H5N1 HPAI viruses. Hum. Vaccin. 7(Suppl):199-204. http://dx.doi.org/10.4161/hv.7.0.14595.
75. Nimmerjahn F, Ravetch JV. 2008. Fcgamma receptors as regulators of immune responses. Nat. Rev. Immunol. 8:34-47. http://dx.doi.org/10.1038/nri2206.
76. Desmyter A, Transue TR, Ghahroudi MA, Thi MH, Poortmans F, Hamers R, Muyldermans S, Wyns L. 1996. Crystal structure of a camel single-domain VH antibody fragment in complex with lysozyme. Nat. Struct. Biol. 3:803-811. http://dx.doi.org/10.1038/nsb0996-803.
77. Colman PM, Laver WG, Varghese JN, Baker AT, Tulloch PA, Air GM, Webster RG. 1987. Three-dimensional structure of a complex of antibody with influenza virus neuraminidase. Nature 326:358-363. http://dx.doi.org/10.1038/326358a0.
78. Malby RL, McCoy AJ, Kortt AA, Hudson PJ, Colman PM. 1998. Three-dimensional structures of single-chain Fv-neuraminidase complexes. J. Mol. Biol. 279:901-910. http://dx.doi.org/10.1006/jmbi.1998.1794.
79. Malby RL, Tulip WR, Harley VR, McKimm-Breschkin JL, Laver WG, Webster RG, Colman PM. 1994. The structure of a complex between the NC10 antibody and influenza virus neuraminidase and comparison with the overlapping binding site of the NC41 antibody. Structure 2:733-746. http://dx.doi.org/10.1016/S0969-2126(00)00074-5.
80. Tulip WR, Varghese JN, Laver WG, Webster RG, Colman PM. 1992. Refined crystal structure of the influenza virus N9 neuraminidase-NC41 Fab complex. J. Mol. Biol. 227:122-148. http://dx.doi.org/10.1016/0022-2836(92)90687-F.
81. De Muynck B, Navarre C, Boutry M. 2010. Production of antibodies in plants: status after twenty years. Plant Biotechnol. J. 8:529-563. http://dx.doi.org/10.1111/j.1467-7652.2009.00494.x.
82. Ismaili A, Jalali-Javaran M, Rasaee MJ, Rahbarizadeh F, Forouzandeh-Moghadam M, Memari HR. 2007. Production and characterization of anti-(mucin MUC1) single-domain antibody in tobacco (Nicotiana tabacum cultivar Xanthi). Biotechnol. Appl. Biochem. 47:11-19. http://dx.doi.org/10.1042/BA20060071.
83. Jobling SA, Jarman C, Teh MM, Holmberg N, Blake C, Verhoeyen ME. 2003. Immunomodulation of enzyme function in plants by single-domain antibody fragments. Nat. Biotechnol. 21:77-80. http://dx.doi.org/10.1038/nbt772.
84. Winichayakul S, Pernthaner A, Scott R, Vlaming R, Roberts N. 2009. Head-to-tail fusions of camelid antibodies can be expressed in planta and bind in rumen fluid. Biotechnol. Appl. Biochem. 53:111-122. http://dx.doi.org/10.1042/BA20080076.
85. De Buck S, Nolf J, De Meyer T, Virdi V, De Wilde K, Van Lerberge E, Van Droogenbroeck B, Depicker A. 2013. Fusion of an Fc chain to aVHH boosts the accumulation levels in Arabidopsis seeds. Plant Biotechnol. J. 11:1006-1016. http://dx.doi.org/10.1111/pbi.12094.