Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation

Immunity

Volumn 48, Issue 2, 2018, Pages 339-349.e5

  Goodwin, Eileen ^a   Gilman, Morgan S A ^b   Wrapp, Daniel ^b   Chen, Man ^c   Ngwuta, Joan O ^c   Moin, Syed M ^c   Bai, Patricia ^b   Sivasubramanian, Arvind ^a   Connor, Ruth I ^b   Wright, Peter F ^b   Graham, Barney S ^c   McLellan, Jason S ^b   Walker, Laura M ^a  

^a Adimab LLC   (United States)

^b DARTMOUTH MEDICAL SCHOOL   (United States)

^c NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

crystal structures; germline; IGHV3 11:IGLV1 40; IGHV3 21:IGLV1 40; naive B cells; pneumoviridae

Indexed keywords

NEUTRALIZING ANTIBODY; RESPIRATORY SYNCYTIAL VIRUS VACCINE; VIRUS ANTIBODY; VIRUS FUSION PROTEIN;

AMINO ACID SEQUENCE; ANTIBODY PRODUCTION; ANTIGEN BINDING; ARTICLE; B LYMPHOCYTE; BINDING SITE; CELL EXPANSION; CLINICAL ARTICLE; CONTROLLED STUDY; FEMALE; HUMAN; INFANT; MALE; NONHUMAN; RESPIRATORY SYNCYTIAL VIRUS INFECTION; SOMATIC HYPERMUTATION; VIRUS NEUTRALIZATION; ANIMAL; BIOSYNTHESIS; IMMUNOLOGY; MOUSE;

ANIMALS; ANTIBODIES, NEUTRALIZING; ANTIBODIES, VIRAL; B-LYMPHOCYTES; HUMANS; INFANT; MICE; RESPIRATORY SYNCYTIAL VIRUS INFECTIONS; RESPIRATORY SYNCYTIAL VIRUS VACCINES; SOMATIC HYPERMUTATION, IMMUNOGLOBULIN; VIRAL FUSION PROTEINS;

EID: 85040793236     PISSN: 10747613     EISSN: 10974180     Source Type: Journal    
DOI: 10.1016/j.immuni.2018.01.005     Document Type: Article

References (66)

1. Acosta, P.L., Caballero, M.T., Polack, F.P., Brief history and characterization of enhanced respiratory syncytial virus disease. Clin. Vaccine Immunol. 23 (2015), 189–195.
2. Adams, P.D., Grosse-Kunstleve, R.W., Hung, L.W., Ioerger, T.R., McCoy, A.J., Moriarty, N.W., Read, R.J., Sacchettini, J.C., Sauter, N.K., Terwilliger, T.C., PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr. D Biol. Crystallogr. 58 (2002), 1948–1954.
3. Anderson, L.J., Hierholzer, J.C., Stone, Y.O., Tsou, C., Fernie, B.F., Identification of epitopes on respiratory syncytial virus proteins by competitive binding immunoassay. J. Clin. Microbiol. 23 (1986), 475–480.
4. Anderson, L.J., Dormitzer, P.R., Nokes, D.J., Rappuoli, R., Roca, A., Graham, B.S., Strategic priorities for respiratory syncytial virus (RSV) vaccine development. Vaccine 31:Suppl 2 (2013), B209–B215.
5. Bailey, J.R., Flyak, A.I., Cohen, V.J., Li, H., Wasilewski, L.N., Snider, A.E., Wang, S., Learn, G.H., Kose, N., Loerinc, L., et al. Broadly neutralizing antibodies with few somatic mutations and hepatitis C virus clearance. JCI Insight, 2, 2017, 92872.
6. Battles, M.B., Langedijk, J.P., Furmanova-Hollenstein, P., Chaiwatpongsakorn, S., Costello, H.M., Kwanten, L., Vranckx, L., Vink, P., Jaensch, S., Jonckers, T.H., et al. Molecular mechanism of respiratory syncytial virus fusion inhibitors. Nat. Chem. Biol. 12 (2016), 87–93.
7. Battye, T.G., Kontogiannis, L., Johnson, O., Powell, H.R., Leslie, A.G., iMOSFLM: a new graphical interface for diffraction-image processing with MOSFLM. Acta Crystallogr. D Biol. Crystallogr. 67 (2011), 271–281.
8. Beeler, J.A., van Wyke Coelingh, K., Neutralization epitopes of the F glycoprotein of respiratory syncytial virus: effect of mutation upon fusion function. J. Virol. 63 (1989), 2941–2950.
9. Burton, D.R., Hangartner, L., Broadly neutralizing antibodies to HIV and their role in vaccine design. Annu. Rev. Immunol. 34 (2016), 635–659.
10. Chen, M., Chang, J.S., Nason, M., Rangel, D., Gall, J.G., Graham, B.S., Ledgerwood, J.E., A flow cytometry-based assay to assess RSV-specific neutralizing antibody is reproducible, efficient and accurate. J. Immunol. Methods 362 (2010), 180–184.
11. Collaborative Computational Project, Number 4. The CCP4 suite: programs for protein crystallography. Acta Crystallogr. D Biol. Crystallogr. 50 (1994), 760–763.
12. Corti, D., Bianchi, S., Vanzetta, F., Minola, A., Perez, L., Agatic, G., Guarino, B., Silacci, C., Marcandalli, J., Marsland, B.J., et al. Cross-neutralization of four paramyxoviruses by a human monoclonal antibody. Nature 501 (2013), 439–443.
13. Crooks, G.E., Hon, G., Chandonia, J.M., Brenner, S.E., WebLogo: a sequence logo generator. Genome Res. 14 (2004), 1188–1190.
14. Emsley, P., Cowtan, K., Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60 (2004), 2126–2132.
15. Esposito, S., Scarselli, E., Lelii, M., Scala, A., Vitelli, A., Capone, S., Fornili, M., Biganzoli, E., Orenti, A., Nicosia, A., et al. Antibody response to respiratory syncytial virus infection in children <18 months old. Hum. Vaccin. Immunother. 12 (2016), 1700–1706.
16. Evans, P.R., Murshudov, G.N., How good are my data and what is the resolution?. Acta Crystallogr. D Biol. Crystallogr. 69 (2013), 1204–1214.
17. Fuentes, S., Coyle, E.M., Beeler, J., Golding, H., Khurana, S., Antigenic fingerprinting following primary RSV infection in young children identifies novel antigenic sites and reveals unlinked evolution of human antibody repertoires to fusion and attachment glycoproteins. PLoS Pathog., 12, 2016, e1005554.
18. García-Barreno, B., Palomo, C., Peñas, C., Delgado, T., Perez-Breña, P., Melero, J.A., Marked differences in the antigenic structure of human respiratory syncytial virus F and G glycoproteins. J. Virol. 63 (1989), 925–932.
19. Gietz, R.D., Schiestl, R.H., High-efficiency yeast transformation using the LiAc/SS carrier DNA/PEG method. Nat. Protoc. 2 (2007), 31–34.
20. Gilman, M.S., Castellanos, C.A., Chen, M., Ngwuta, J.O., Goodwin, E., Moin, S.M., Mas, V., Melero, J.A., Wright, P.F., Graham, B.S., et al. Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors. Sci. Immunol., 1, 2016, 1.
21. Glezen, W.P., Taber, L.H., Frank, A.L., Kasel, J.A., Risk of primary infection and reinfection with respiratory syncytial virus. Am. J. Dis. Child. 140 (1986), 543–546.
22. Graham, B.S., Vaccine development for respiratory syncytial virus. Curr. Opin. Virol. 23 (2017), 107–112.
23. Griffin, M.P., Khan, A.A., Esser, M.T., Jensen, K., Takas, T., Kankam, M.K., Villafana, T., Dubovsky, F., Safety, tolerability, and pharmacokinetics of MEDI8897, the respiratory syncytial virus prefusion F-targeting monoclonal antibody with an extended half-life, in healthy adults. Antimicrob. Agents Chemother. 61 (2017), e01714–e01716.
24. Hall, C.B., Walsh, E.E., Long, C.E., Schnabel, K.C., Immunity to and frequency of reinfection with respiratory syncytial virus. J. Infect. Dis. 163 (1991), 693–698.
25. Homaira, N., Rawlinson, W., Snelling, T.L., Jaffe, A., Effectiveness of palivizumab in preventing RSV hospitalization in high risk children: a real-world perspective. Int. J. Pediatr., 2014, 2014, 571609.
26. Huang, K., Incognito, L., Cheng, X., Ulbrandt, N.D., Wu, H., Respiratory syncytial virus-neutralizing monoclonal antibodies motavizumab and palivizumab inhibit fusion. J. Virol. 84 (2010), 8132–8140.
27. Jain, T., Sun, T., Durand, S., Hall, A., Houston, N.R., Nett, J.H., Sharkey, B., Bobrowicz, B., Caffry, I., Yu, Y., et al. Biophysical properties of the clinical-stage antibody landscape. Proc. Natl. Acad. Sci. USA 114 (2017), 944–949.
28. Jans, J., Pettengill, M., Kim, D., van der Made, C., de Groot, R., Henriet, S., de Jonge, M.I., Ferwerda, G., Levy, O., Human newborn B cells mount an interferon-α/β receptor-dependent humoral response to respiratory syncytial virus. J. Allergy Clin. Immunol. 139 (2017), 1997–2000.e4.
29. Kamal-Bahl, S., Doshi, J., Campbell, J., Economic analyses of respiratory syncytial virus immunoprophylaxis in high-risk infants: a systematic review. Arch. Pediatr. Adolesc. Med. 156 (2002), 1034–1041.
30. Killikelly, A.M., Kanekiyo, M., Graham, B.S., Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus. Sci. Rep., 6, 2016, 34108.
31. Krarup, A., Truan, D., Furmanova-Hollenstein, P., Bogaert, L., Bouchier, P., Bisschop, I.J., Widjojoatmodjo, M.N., Zahn, R., Schuitemaker, H., McLellan, J.S., Langedijk, J.P., A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism. Nat. Commun., 6, 2015, 8143.
32. Kwakkenbos, M.J., Diehl, S.A., Yasuda, E., Bakker, A.Q., van Geelen, C.M., Lukens, M.V., van Bleek, G.M., Widjojoatmodjo, M.N., Bogers, W.M., Mei, H., et al. Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming. Nat. Med. 16 (2010), 123–128.
33. Lambert, D.M., Barney, S., Lambert, A.L., Guthrie, K., Medinas, R., Davis, D.E., Bucy, T., Erickson, J., Merutka, G., Petteway, S.R. Jr., Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion. Proc. Natl. Acad. Sci. USA 93 (1996), 2186–2191.
34. Lambert, L., Sagfors, A.M., Openshaw, P.J., Culley, F.J., Immunity to RSV in early-life. Front. Immunol., 5, 2014, 466.
35. Legg, J.P., Hussain, I.R., Warner, J.A., Johnston, S.L., Warner, J.O., Type 1 and type 2 cytokine imbalance in acute respiratory syncytial virus bronchiolitis. Am. J. Respir. Crit. Care Med. 168 (2003), 633–639.
36. Lerner, R.A., Rare antibodies from combinatorial libraries suggests an S.O.S. component of the human immunological repertoire. Mol. Biosyst. 7 (2011), 1004–1012.
37. McCoy, A.J., Grosse-Kunstleve, R.W., Adams, P.D., Winn, M.D., Storoni, L.C., Read, R.J., Phaser crystallographic software. J. Appl. Cryst. 40 (2007), 658–674.
38. McLellan, J.S., Chen, M., Chang, J.S., Yang, Y., Kim, A., Graham, B.S., Kwong, P.D., Structure of a major antigenic site on the respiratory syncytial virus fusion glycoprotein in complex with neutralizing antibody 101F. J. Virol. 84 (2010), 12236–12244.
39. McLellan, J.S., Chen, M., Kim, A., Yang, Y., Graham, B.S., Kwong, P.D., Structural basis of respiratory syncytial virus neutralization by motavizumab. Nat. Struct. Mol. Biol. 17 (2010), 248–250.
40. McLellan, J.S., Yang, Y., Graham, B.S., Kwong, P.D., Structure of respiratory syncytial virus fusion glycoprotein in the postfusion conformation reveals preservation of neutralizing epitopes. J. Virol. 85 (2011), 7788–7796.
41. McLellan, J.S., Chen, M., Leung, S., Graepel, K.W., Du, X., Yang, Y., Zhou, T., Baxa, U., Yasuda, E., Beaumont, T., et al. Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science 340 (2013), 1113–1117.
42. Morin, A., Eisenbraun, B., Key, J., Sanschagrin, P.C., Timony, M.A., Ottaviano, M., Sliz, P., Collaboration gets the most out of software. eLife, 2, 2013, e01456.
43. Mousa, J.J., Kose, N., Matta, P., Gilchuk, P., Crowe, J.E. Jr., A novel pre-fusion conformation-specific neutralizing epitope on the respiratory syncytial virus fusion protein. Nat. Microbiol., 2, 2017, 16271.
44. Murphy, B.R., Walsh, E.E., Formalin-inactivated respiratory syncytial virus vaccine induces antibodies to the fusion glycoprotein that are deficient in fusion-inhibiting activity. J. Clin. Microbiol. 26 (1988), 1595–1597.
45. Murphy, B.R., Alling, D.W., Snyder, M.H., Walsh, E.E., Prince, G.A., Chanock, R.M., Hemming, V.G., Rodriguez, W.J., Kim, H.W., Graham, B.S., et al. Effect of age and preexisting antibody on serum antibody response of infants and children to the F and G glycoproteins during respiratory syncytial virus infection. J. Clin. Microbiol. 24 (1986), 894–898.
46. Panda, S., Ding, J.L., Natural antibodies bridge innate and adaptive immunity. J. Immunol. 194 (2015), 13–20.
47. PATH (2017). RSV Vaccine and mAb Snapshot. https://www.path.org/publications/files/CVIA_RSV_snapshot_fs.pdf.
48. Polack, F.P., Teng, M.N., Collins, P.L., Prince, G.A., Exner, M., Regele, H., Lirman, D.D., Rabold, R., Hoffman, S.J., Karp, C.L., et al. A role for immune complexes in enhanced respiratory syncytial virus disease. J. Exp. Med. 196 (2002), 859–865.
49. Potterton, E., Briggs, P., Turkenburg, M., Dodson, E., A graphical user interface to the CCP4 program suite. Acta Crystallogr. D Biol. Crystallogr. 59 (2003), 1131–1137.
50. Rechavi, E., Lev, A., Lee, Y.N., Simon, A.J., Yinon, Y., Lipitz, S., Amariglio, N., Weisz, B., Notarangelo, L.D., Somech, R., Timely and spatially regulated maturation of B and T cell repertoire during human fetal development. Sci. Transl. Med., 7, 2015, 276ra25.
51. Reed, J.H., Jackson, J., Christ, D., Goodnow, C.C., Clonal redemption of autoantibodies by somatic hypermutation away from self-reactivity during human immunization. J. Exp. Med. 213 (2016), 1255–1265.
52. Ridings, J., Dinan, L., Williams, R., Roberton, D., Zola, H., Somatic mutation of immunoglobulin V(H)6 genes in human infants. Clin. Exp. Immunol. 114 (1998), 33–39.
53. Sande, C.J., Cane, P.A., Nokes, D.J., The association between age and the development of respiratory syncytial virus neutralising antibody responses following natural infection in infants. Vaccine 32 (2014), 4726–4729.
54. Sastre, P., Melero, J.A., García-Barreno, B., Palomo, C., Comparison of affinity chromatography and adsorption to vaccinia virus recombinant infected cells for depletion of antibodies directed against respiratory syncytial virus glycoproteins present in a human immunoglobulin preparation. J. Med. Virol. 76 (2005), 248–255.
55. Shi, T., McAllister, D.A., O'Brien, K.L., Simoes, E.A.F., Madhi, S.A., Gessner, B.D., Polack, F.P., Balsells, E., Acacio, S., Aguayo, C., et al., RSV Global Epidemiology Network. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet 390 (2017), 946–958.
56. Shinoff, J.J., O'Brien, K.L., Thumar, B., Shaw, J.B., Reid, R., Hua, W., Santosham, M., Karron, R.A., Young infants can develop protective levels of neutralizing antibody after infection with respiratory syncytial virus. J. Infect. Dis. 198 (2008), 1007–1015.
57. Siegrist, C.A., Aspinall, R., B-cell responses to vaccination at the extremes of age. Nat. Rev. Immunol. 9 (2009), 185–194.
58. Swers, J.S., Kellogg, B.A., Wittrup, K.D., Shuffled antibody libraries created by in vivo homologous recombination and yeast surface display. Nucleic Acids Res., 32, 2004, e36.
59. The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 102 (1998), 531–537.
60. Thomson, C.A., Bryson, S., McLean, G.R., Creagh, A.L., Pai, E.F., Schrader, J.W., Germline V-genes sculpt the binding site of a family of antibodies neutralizing human cytomegalovirus. EMBO J. 27 (2008), 2592–2602.
61. Tiller, T., Meffre, E., Yurasov, S., Tsuiji, M., Nussenzweig, M.C., Wardemann, H., Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J. Immunol. Methods 329 (2008), 112–124.
62. Wen, X., Mousa, J.J., Bates, J.T., Lamb, R.A., Crowe, J.E. Jr., Jardetzky, T.S., Structural basis for antibody cross-neutralization of respiratory syncytial virus and human metapneumovirus. Nat. Microbiol., 2, 2017, 16272.
63. Williams, J.V., Weitkamp, J.H., Blum, D.L., LaFleur, B.J., Crowe, J.E. Jr., The human neonatal B cell response to respiratory syncytial virus uses a biased antibody variable gene repertoire that lacks somatic mutations. Mol. Immunol. 47 (2009), 407–414.
64. Wu, S.J., Schmidt, A., Beil, E.J., Day, N.D., Branigan, P.J., Liu, C., Gutshall, L.L., Palomo, C., Furze, J., Taylor, G., et al. Characterization of the epitope for anti-human respiratory syncytial virus F protein monoclonal antibody 101F using synthetic peptides and genetic approaches. J. Gen. Virol. 88 (2007), 2719–2723.
65. Yeung, Y.A., Foletti, D., Deng, X., Abdiche, Y., Strop, P., Glanville, J., Pitts, S., Lindquist, K., Sundar, P.D., Sirota, M., et al. Germline-encoded neutralization of a Staphylococcus aureus virulence factor by the human antibody repertoire. Nat. Commun., 7, 2016, 13376.
66. Zhu, Q., McLellan, J.S., Kallewaard, N.L., Ulbrandt, N.D., Palaszynski, S., Zhang, J., Moldt, B., Khan, A., Svabek, C., McAuliffe, J.M., et al. A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants. Sci. Transl. Med., 9, 2017, aaj1928.