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Committing the Oldest Sins in the Newest Kind of Ways—Antibodies Targeting the Influenza Virus Type A Hemagglutinin Globular Head

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  • Authors: Jens C. Krause1, James E. Crowe, JR.2
  • Editors: James E. Crowe Jr.3, Diana Boraschi4, Rino Rappuoli5
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Children's Hospital, University of Freiburg Medical Center, 79106 Freiburg, Germany; 2: Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232-0417; 3: Vanderbilt University School of Medicine, Nashville, TN; 4: National Research Council, Pisa, Italy; 5: Novartis Vaccines, Siena, Italy
  • Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.AID-0021-2014
  • Received 14 July 2014 Accepted 17 July 2014 Published 24 October 2014
  • James E. Crowe, Jr., MD, james.crowe@vanderbilt.edu
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  • Abstract:

    The globular head of the trimeric influenza hemagglutinin (HA) contains the receptor-binding domain (RBD) and is the target of potently neutralizing human monoclonal antibodies (mAbs) with high activity. In general, these mAbs are induced easily by vaccination, but only infrequently display cross-neutralizing activity against antigenic drift variants or even against HA molecules from viruses of heterologous subtypes. Recently, the atomic resolution structures of several such antibodies in complex with HA have been determined by X-ray crystallography. Not surprisingly, cross-reactive globular head antibodies target, at least partially, the conserved RBD. The cross-reactive potential of such mAbs is limited by contacts of hypervariable HA residues outside the conserved RBD. The RBD of H2 HA seems especially immunogenic. Increasing the immunogenicity of the RBD of other HA subtypes may be a step toward a universal influenza vaccine. The germ line-encoded Phe54 residue of the CDR-H2 of the V1-69 germ line sequence appears to be ideally suited not only to reach into a conserved, hydrophobic pocket on the HA stem, but also to reach into the conserved, hydrophobic pocket that is the RBD. We have cloned antibodies from different individuals that are encoded by the V1-69 germ line gene segment that contact the universally conserved Trp153 on the bottom of the RBD. These antibodies serve as further evidence of antibody genetic sequence convergence across individuals.

  • Citation: Krause J, Crowe, JR. J. 2014. Committing the Oldest Sins in the Newest Kind of Ways—Antibodies Targeting the Influenza Virus Type A Hemagglutinin Globular Head. Microbiol Spectrum 2(5):AID-0021-2014. doi:10.1128/microbiolspec.AID-0021-2014.

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Viral Proteins
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References

1. Wilson IA, Skehel JJ, Wiley DC. 1981. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature 289:366–373. [PubMed][CrossRef]
2. Xu R, Ekiert DC, Krause JC, Hai R, Crowe JEJ, Wilson IA. 2010. Structural basis of preexisting immunity to the 2009 H1N1 pandemic influenza virus. Science 328:357–360. [PubMed][CrossRef]
3. Corti D, Voss J, Gamblin SJ, Codoni G, Macagno A, Jarrossay D, Vachieri SG, Pinna D, Minola A, Vanzetta F, Silacci C, Fernandez-Rodriguez BM, Agatic G, Bianchi S, Giacchetto-Sasselli I, Calder L, Sallusto F, Collins P, Haire LF, Temperton N, Langedijk JP, Skehel JJ, Lanzavecchia A. 2011. A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science 333:850–856. [PubMed][CrossRef]
4. Ekiert DC, Friesen RH, Bhabha G, Kwaks T, Jongeneelen M, Yu W, Ophorst C, Cox F, Korse HJ, Brandenburg B, Vogels R, Brakenhoff JP, Kompier R, Koldijk MH, Cornelissen LA, Poon LL, Peiris M, Koudstaal W, Wilson IA, Goudsmit J. 2011. A highly conserved neutralizing epitope on group 2 influenza A viruses. Science 333:843–850. [PubMed][CrossRef]
5. Okuno Y, Isegawa Y, Sasao F, Ueda S. 1993. A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains. J Virol 67:2552–2558. [PubMed]
6. Wrammert J, Koutsonanos D, Li GM, Edupuganti S, Sui J, Morrissey M, McCausland M, Skountzou I, Hornig M, Lipkin WI, Mehta A, Razavi B, Del Rio C, Zheng NY, Lee JH, Huang M, Ali Z, Kaur K, Andrews S, Amara RR, Wang Y, Das SR, O'Donnell CD, Yewdell JW, Subbarao K, Marasco WA, Mulligan MJ, Compans R, Ahmed R, Wilson PC. 2011. Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med 208:181–193. [PubMed][CrossRef]
7. Davenport FM, Hennessy AV, Francis T, Jr. 1953. Epidemiologic and immunologic significance of age distribution of antibody to antigenic variants of influenza virus. J Exp Med 98:641–656. [PubMed][CrossRef]
8. Fish S, Zenowich E, Fleming M, Manser T. 1989. Molecular analysis of original antigenic sin. I. Clonal selection, somatic mutation, and isotype switching during a memory B cell response. J Exp Med 170:1191–1209. [PubMed][CrossRef]
9. Krause R. 2006. The swine flu episode and the fog of epidemics. Emerg Infect Dis 12:40–43. [PubMed][CrossRef]
10. Wrammert J, Smith K, Miller J, Langley WA, Kokko K, Larsen C, Zheng NY, Mays I, Garman L, Helms C, James J, Air GM, Capra JD, Ahmed R, Wilson PC. 2008. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature 453:667–671. [PubMed][CrossRef]
11. Palese P, Wang TT. 30 August 2011. Why do influenza virus subtypes die out? A hypothesis. MBio doi:10.1128/mBio.00150-11. [PubMed][CrossRef]
12. Wrammert J, Onlamoon N, Akondy RS, Perng GC, Polsrila K, Chandele A, Kwissa M, Pulendran B, Wilson PC, Wittawatmongkol O, Yoksan S, Angkasekwinai N, Pattanapanyasat K, Chokephaibulkit K, Ahmed R. 2012. Rapid and massive virus-specific plasmablast responses during acute dengue virus infection in humans. J Virol 86:2911–2918. [PubMed][CrossRef]
13. Krause JC, Tsibane T, Tumpey TM, Huffman CJ, Basler CF, Crowe JE. 2011. A broadly neutralizing human monoclonal antibody that recognizes a conserved, novel epitope on the globular head of the influenza H1N1 virus hemagglutinin. J Virol 85:10905–10908. [PubMed][CrossRef]
14. Krause JC, Tsibane T, Tumpey TM, Huffman CJ, Briney BS, Smith SA, Basler CF, Crowe JE, Jr. 2011. Epitope-specific human influenza antibody repertoires diversify by B cell intraclonal sequence divergence and interclonal convergence. J Immunol 187:3704–3711. [PubMed][CrossRef]
15. Whittle JR, Zhang R, Khurana S, King LR, Manischewitz J, Golding H, Dormitzer PR, Haynes BF, Walter EB, Moody MA, Kepler TB, Liao HX, Harrison SC. 2011. Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. Proc Natl Acad Sci USA 108:14216–14221. [PubMed][CrossRef]
16. Krause JC, Tsibane T, Tumpey TM, Huffman CJ, Albrecht R, Blum DL, Ramos I, Fernandez-Sesma A, Edwards KM, García-Sastre A, Basler CF, Crowe JE. 2012. Human monoclonal antibodies to pandemic 1957 H2N2 and pandemic 1968 H3N2 influenza viruses. J Virol 86:6334–6340. [PubMed][CrossRef]
17. Xu R, Krause JC, McBride R, Paulson JC, Crowe JE, Wilson IA. 2013. A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin. Nat Struct Mol Biol 20:363–370. [PubMed][CrossRef]
18. National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Food and Drug Administration. 2012. Universal Influenza Vaccines Meeting Summary. 19 to 20 June 2012.
19. Caton AJ, Brownlee GG, Yewdell JW, Gerhard W. 1982. The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell 31:417–427. [PubMed][CrossRef]
20. Krause JC, Tumpey TM, Huffman CJ, McGraw PA, Pearce MB, Tsibane T, Hai R, Basler CF, Crowe JE. 2010. Naturally occurring human monoclonal antibodies neutralize both 1918 and 2009 pandemic influenza A (H1N1) viruses. J Virol 84:3127–3130. [PubMed][CrossRef]
21. Manicassamy B, Medina RA, Hai R, Tsibane T, Stertz S, Nistal-Villan E, Palese P, Basler CF, Garcia-Sastre A. 2010. Protection of mice against lethal challenge with 2009 H1N1 influenza A virus by 1918-like and classical swine H1N1 based vaccines. PLoS Pathog 6:e1000745. doi: 10.1371/journal.ppat.1000745. [PubMed][CrossRef]
22. Brownlee GG, Fodor E. 2001. The predicted antigenicity of the haemagglutinin of the 1918 Spanish influenza pandemic suggests an avian origin. Philos Trans R Soc Lond B Biol Sci 356:1871–1876. [PubMed][CrossRef]
23. Tsibane T, Ekiert DC, Krause JC, Martinez O, Crowe JE, Wilson IA, Basler CF. 2012. Influenza human monoclonal antibody 1F1 interacts with three major antigenic sites and residues mediating human receptor specificity in H1N1 viruses. PLoS Pathog 8:e1003067. doi:10.1371/journal.ppat.1003067. [PubMed][CrossRef]
24. Wiley DC, Wilson IA, Skehel JJ. 1981. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 289:373–378. [PubMed][CrossRef]
25. Fleury D, Wharton SA, Skehel JJ, Knossow M, Bizebard T. 1998. Antigen distortion allows influenza virus to escape neutralization. Nat Struct Biol 5:119–123. [PubMed][CrossRef]
26. Fleury D, Barrere B, Bizebard T, Daniels RS, Skehel JJ, Knossow M. 1999. A complex of influenza hemagglutinin with a neutralizing antibody that binds outside the virus receptor binding site. Nat Struct Biol 6:530–534. [PubMed][CrossRef]
27. Fleury D, Daniels RS, Skehel JJ, Knossow M, Bizebard T. 2000. Structural evidence for recognition of a single epitope by two distinct antibodies. Proteins 40:572–578. [PubMed][CrossRef]
28. Barbey-Martin C, Gigant B, Bizebard T, Calder LJ, Wharton SA, Skehel JJ, Knossow M. 2002. An antibody that prevents the hemagglutinin low pH fusogenic transition. Virology 294:70–74. [PubMed][CrossRef]
29. Knossow M, Skehel JJ. 2006. Variation and infectivity neutralization in influenza. Immunology 119:1–7. [PubMed][CrossRef]
30. Yamada A, Brown LE, Webster RG. 1984. Characterization of H2 influenza virus hemagglutinin with monoclonal antibodies: influence of receptor specificity. Virology 138:276–286. [PubMed][CrossRef]
31. Connor RJ, Kawaoka Y, Webster RG, Paulson JC. 1994. Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology 205:17–23. [PubMed][CrossRef]
32. Krause JC, Ekiert DC, Tumpey TM, Smith PB, Wilson IA, Crowe JE, Jr. 2011. An insertion mutation that distorts antibody binding site architecture enhances function of a human antibody. MBio 2:e00345-10. doi:10.1128/mBio.00345-10. [PubMed][CrossRef]
33. Yu X, Tsibane T, McGraw PA, House FS, Keefer CJ, Hicar MD, Tumpey TM, Pappas C, Perrone LA, Martinez O, Stevens J, Wilson IA, Aguilar PV, Altschuler EL, Basler CF, Crowe JE, Jr. 2008. Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature 455:532–536. [PubMed][CrossRef]
34. Shope RE. 1931. Swine influenza. I. Experimental transmission and pathology. J Exp Med 54:349–359. [PubMed][CrossRef]
35. Wei CJ, Boyington JC, Dai K, Houser KV, Pearce MB, Kong WP, Yang ZY, Tumpey TM, Nabel GJ. 2010. Cross-neutralization of 1918 and 2009 influenza viruses: role of glycans in viral evolution and vaccine design. Sci Transl Med 2:24ra21. doi:10.1126/scitranslmed.3000799. [PubMed][CrossRef]
36. Herzenberg LA, Black SJ, Tokuhisa T. 1980. Memory B cells at successive stages of differentiation. Affinity maturation and the role of IgD receptors. J Exp Med 151:1071–1087. [PubMed][CrossRef]
37. Gamblin SJ, Haire LF, Russell RJ, Stevens DJ, Xiao B, Ha Y, Vasisht N, Steinhauer DA, Daniels RS, Elliot A, Wiley DC, Skehel JJ. 2004. The structure and receptor binding properties of the 1918 influenza hemagglutinin. Science 303:1838–1842. [PubMed][CrossRef]
38. Stevens J, Corper AL, Basler CF, Taubenberger JK, Palese P, Wilson IA. 2004. Structure of the uncleaved human H1 hemagglutinin from the extinct 1918 influenza virus. Science 303:1866–1870. [PubMed][CrossRef]
39. Glaser L, Stevens J, Zamarin D, Wilson IA, Garcia-Sastre A, Tumpey TM, Basler CF, Taubenberger JK, Palese P. 2005. A single amino acid substitution in 1918 influenza virus hemagglutinin changes receptor binding specificity. J Virol 79:11533–11536. [PubMed][CrossRef]
40. Stevens J, Blixt O, Glaser L, Taubenberger JK, Palese P, Paulson JC, Wilson IA. 2006. Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities. J Mol Biol 355:1143–1155. [PubMed][CrossRef]
41. Colman PM, Tulip WR, Varghese JN, Tulloch PA, Baker AT, Laver WG, Air GM, Webster RG. 1989. Three-dimensional structures of influenza virus neuraminidase-antibody complexes. Philos Trans R Soc Lond B Biol Sci 323:511–518. [PubMed][CrossRef]
42. Naeve CW, Hinshaw VS, Webster RG. 1984. Mutations in the hemagglutinin receptor-binding site can change the biological properties of an influenza virus. J Virol 51:567–569. [PubMed]
43. Daniels PS, Jeffries S, Yates P, Schild GC, Rogers GN, Paulson JC, Wharton SA, Douglas AR, Skehel JJ, Wiley DC. 1987. The receptor-binding and membrane-fusion properties of influenza virus variants selected using anti-haemagglutinin monoclonal antibodies. EMBO J 6:1459–1465. [PubMed]
44. Schmidt AG, Xu H, Khan AR, O'Donnell T, Khurana S, King LR, Manischewitz J, Golding H, Suphaphiphat P, Carfi A, Settembre EC, Dormitzer PR, Kepler TB, Zhang R, Moody MA, Haynes BF, Liao H-X, Shaw DE, Harrison SC. 2013. Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody. Proc Natl Acad Sci USA 110:264–269. [PubMed][CrossRef]
45. Hong M, Lee PS, Hoffman RMB, Zhu X, Krause JC, Laursen NS, Yoon S-I, Song L, Tussey L, Crowe JE, Ward AB, Wilson IA. 2013. Antibody recognition of the pandemic H1N1 Influenza virus hemagglutinin receptor binding site. J Virol 87:12471–12480. [PubMed][CrossRef]
46. Ohshima N, Iba Y, Kubota-Koketsu R, Asano Y, Okuno Y, Kurosawa Y. 2011. Naturally occurring antibodies in humans can neutralize a variety of influenza virus strains, including H3, H1, H2, and H5. J Virol 85:11048–11057. [PubMed][CrossRef]
47. Yoshida R, Igarashi M, Ozaki H, Kishida N, Tomabechi D, Kida H, Ito K, Takada A. 2009. Cross-protective potential of a novel monoclonal antibody directed against antigenic site B of the hemagglutinin of influenza A viruses. PLoS Pathog 5:e1000350. doi:10.1371/journal.ppat.1000350. [PubMed][CrossRef]
48. Lee PS, Yoshida R, Ekiert DC, Sakai N, Suzuki Y, Takada A, Wilson IA. 2012. Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity. Proc Natl Acad Sci USA 109:17040–17045. [PubMed][CrossRef]
49. Ekiert DC, Kashyap AK, Steel J, Rubrum A, Bhabha G, Khayat R, Lee JH, Dillon MA, O'Neil RE, Faynboym AM, Horowitz M, Horowitz L, Ward AB, Palese P, Webby R, Lerner RA, Bhatt RR, Wilson IA. 2012. Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature 489:526–532. [PubMed][CrossRef]
50. Thornburg NJ, Nannemann DP, Blum DL, Belser JA, Tumpey TM, Desphande S, Fritz GA, Sapparapu G, Krause JC, Lee JH, Warm AB, Lee DE, Li S, Winarski KL, Spiller BW, Meiler J, Crowe JE, Jr. 2013. Human antibodies that neutralize respiratory droplet transmissible H5N1 influenza viruses. J Clin Invest 123:4405–4409. [PubMed][CrossRef]
51. Fleishman SJ, Whitehead TA, Ekiert DC, Dreyfus C, Corn JE, Strauch EM, Wilson IA, Baker D. 2011. Computational design of proteins targeting the conserved stem region of influenza hemagglutinin. Science 332:816–821. [PubMed][CrossRef]
52. Whitehead TA, Chevalier A, Song Y, Dreyfus C, Fleishman SJ, De Mattos C, Myers CA, Kamisetty H, Blair P, Wilson IA, Baker D. 2012. Optimization of affinity, specificity and function of designed influenza inhibitors using deep sequencing. Nat Biotechnol 30:543–548. [PubMed][CrossRef]
53. Wei C-J, Yassine HM, McTamney PM, Gall JG, Whittle JR, Boyington JC, Nabel GJ. 2012. Elicitation of broadly neutralizing influenza antibodies in animals with previous influenza exposure. Sci Transl Med 4:147ra114. doi:10.1126/scitranslmed.3004273. [PubMed][CrossRef]
54. Khurana S, Chearwae W, Castellino F, Manischewitz J, King LR, Honorkiewicz A, Rock MT, Edwards KM, Del Giudice G, Rappuoli R, Golding H. 2010. Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus. Sci Transl Med 2:15ra5. doi:10.1126/scitranslmed.3000624. [PubMed][CrossRef]
55. Haynes BF, Kelsoe G, Harrison SC, Kepler TB. 2012. B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study. Nat Biotechnol 30:423–433. [PubMed][CrossRef]
56. Medina RA, Stertz S, Manicassamy B, Zimmermann P, Sun X, Albrecht RA, Uusi-Kerttula H, Zagordi O, Belshe RB, Frey SE, Tumpey TM, Garcia-Sastre A. 2013. Glycosylations in the globular head of the hemagglutinin protein modulate the virulence and antigenic properties of the H1N1 influenza viruses. Sci Transl Med 5:187ra70. doi:10.1126/scitranslmed.3005996. [PubMed][CrossRef]
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2014-10-24
2017-04-23

Abstract:

The globular head of the trimeric influenza hemagglutinin (HA) contains the receptor-binding domain (RBD) and is the target of potently neutralizing human monoclonal antibodies (mAbs) with high activity. In general, these mAbs are induced easily by vaccination, but only infrequently display cross-neutralizing activity against antigenic drift variants or even against HA molecules from viruses of heterologous subtypes. Recently, the atomic resolution structures of several such antibodies in complex with HA have been determined by X-ray crystallography. Not surprisingly, cross-reactive globular head antibodies target, at least partially, the conserved RBD. The cross-reactive potential of such mAbs is limited by contacts of hypervariable HA residues outside the conserved RBD. The RBD of H2 HA seems especially immunogenic. Increasing the immunogenicity of the RBD of other HA subtypes may be a step toward a universal influenza vaccine. The germ line-encoded Phe54 residue of the CDR-H2 of the V1-69 germ line sequence appears to be ideally suited not only to reach into a conserved, hydrophobic pocket on the HA stem, but also to reach into the conserved, hydrophobic pocket that is the RBD. We have cloned antibodies from different individuals that are encoded by the V1-69 germ line gene segment that contact the universally conserved Trp153 on the bottom of the RBD. These antibodies serve as further evidence of antibody genetic sequence convergence across individuals.

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FIGURE 1

Space-filling model of influenza hemagglutinin HA based on PDB 1RD8 ( 38 ). The three protomers of the HA trimer are colored white, gray, or black. doi:10.1128/microbiolspec.AID-0021-2014.f1

Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.AID-0021-2014
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TABLE 1

Characteristics of globular head versus stem HA antibodies

Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.AID-0021-2014
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TABLE 2

Select cross-reactive globular head HA antibodies

Source: microbiolspec October 2014 vol. 2 no. 5 doi:10.1128/microbiolspec.AID-0021-2014

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