Antigenicity of the 2015–2016 seasonal H1N1 human influenza virus HA and NA proteins

PLoS ONE

Volumn 12, Issue 11, 2017, Pages

  Clark, Amelia M ^a   DeDiego, Marta L ^a   Anderson, Christopher S ^a   Wang, Jiong ^a   Yang, Hongmei ^a   Nogales, Aitor ^a   Martinez Sobrido, Luis ^a   Zand, Martin S ^a   Sangster, Mark Y ^a   Topham, David J ^a  

^a UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HEMAGGLUTININ; NEUTRALIZING ANTIBODY; SIALIDASE; INFLUENZA VIRUS HEMAGGLUTININ; VIRUS ANTIGEN;

2009 H1N1 INFLUENZA; ADULT; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANIMAL CELL; ANTIBODY BLOOD LEVEL; ANTIBODY TITER; ANTIGENICITY; ARTICLE; BLOOD ANALYSIS; CONTROLLED STUDY; FEMALE; HUMAN; HUMAN CELL; INFECTION RISK; INFLUENZA A VIRUS (H1N1); MALE; NEW YORK; NONHUMAN; NOSE SMEAR; PROTEIN BINDING; SEASONAL INFLUENZA; SEQUENCE ANALYSIS; VIRUS ISOLATION; ANIMAL; DOG; IMMUNOLOGY; INFLUENZA; SEASON; VIROLOGY;

ANIMALS; ANTIGENS, VIRAL; DOGS; HEMAGGLUTININ GLYCOPROTEINS, INFLUENZA VIRUS; HUMANS; INFLUENZA A VIRUS, H1N1 SUBTYPE; INFLUENZA, HUMAN; NEURAMINIDASE; NEW YORK; SEASONS;

EID: 85034057016     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0188267     Document Type: Article

References (88)

1. Webster RG, Bean WJ Jr. (1978) Genetics of influenza virus. Annu Rev Genet 12: 415–431. https://doi.org/10.1146/annurev.ge.12.120178.002215 PMID: 371528
2. Klenk HD, Garten W (1994) Host cell proteases controlling virus pathogenicity. Trends Microbiol 2: 39–43. PMID: 8162439
3. Wilson IA, Skehel JJ, Wiley DC (1981) Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature 289: 366–373. PMID: 7464906
4. 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. PMID: 6186384
5. Weis W, Brown JH, Cusack S, Paulson JC, Skehel JJ, Wiley DC (1988) Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid. Nature 333: 426–431. https://doi.org/10.1038/ 333426a0 PMID: 3374584
6. Hamilton BS, Whittaker GR, Daniel S (2012) Influenza virus-mediated membrane fusion: determinants of hemagglutinin fusogenic activity and experimental approaches for assessing virus fusion. Viruses 4: 1144–1168. https://doi.org/10.3390/v4071144 PMID: 22852045
7. Skehel JJ, Wiley DC (2000) Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 69: 531–569. https://doi.org/10.1146/annurev.biochem.69.1.531 PMID: 10966468
8. ECDC (2016) Influenza virus characterisation, summary Europe, June 2016. Stockholm: European Centre for Disease Prevention and Control.
9. Krause JC, Tumpey TM, Huffman CJ, McGraw PA, Pearce MB, Tsibane T, et al. (2010) Naturally occurring human monoclonal antibodies neutralize both 1918 and 2009 pandemic influenza A (H1N1) viruses. J Virol 84: 3127–3130. https://doi.org/10.1128/JVI.02184-09 PMID: 20042511
10. Colman PM, Ward CW (1985) Structure and diversity of influenza virus neuraminidase. Curr Top Microbiol Immunol 114: 177–255. PMID: 2581739
11. Cohen M, Zhang XQ, Senaati HP, Chen HW, Varki NM, Schooley RT, et al. (2013) Influenza A penetrates host mucus by cleaving sialic acids with neuraminidase. Virol J 10: 321. https://doi.org/10.1186/ 1743-422X-10-321 PMID: 24261589
12. Varghese JN, Laver WG, Colman PM (1983) Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 A resolution. Nature 303: 35–40. PMID: 6843658
13. Hensley SE (2014) Challenges of selecting seasonal influenza vaccine strains for humans with diverse pre-exposure histories. Curr Opin Virol 8: 85–89. https://doi.org/10.1016/j.coviro.2014.07.007 PMID: 25108824
14. Neu KE, Henry Dunand CJ, Wilson PC (2016) Heads, stalks and everything else: how can antibodies eradicate influenza as a human disease? Curr Opin Immunol 42: 48–55. https://doi.org/10.1016/j.coi.2016.05.012 PMID: 27268395
15. Corti D, Cameroni E, Guarino B, Kallewaard NL, Zhu Q, Lanzavecchia A (2017) Tackling influenza with broadly neutralizing antibodies. Curr Opin Virol 24: 60–69. https://doi.org/10.1016/j.coviro.2017.03.002 PMID: 28527859
16. Wohlbold TJ, Krammer F (2014) In the shadow of hemagglutinin: a growing interest in influenza viral neuraminidase and its role as a vaccine antigen. Viruses 6: 2465–2494. https://doi.org/10.3390/ v6062465 PMID: 24960271
17. Margine I, Hai R, Albrecht RA, Obermoser G, Harrod AC, Banchereau J, et al. (2013) H3N2 influenza virus infection induces broadly reactive hemagglutinin stalk antibodies in humans and mice. J Virol 87: 4728–4737. https://doi.org/10.1128/JVI.03509-12 PMID: 23408625
18. Ekiert DC, Bhabha G, Elsliger MA, Friesen RH, Jongeneelen M, Throsby M, et al. (2009) Antibody recognition of a highly conserved influenza virus epitope. Science 324: 246–251. https://doi.org/10.1126/science.1171491 PMID: 19251591
19. Laguio-Vila MR, Thompson MG, Reynolds S, Spencer SM, Gaglani M, Naleway A, et al. (2015) Comparison of serum hemagglutinin and neuraminidase inhibition antibodies after 2010–2011 trivalent inactivated influenza vaccination in healthcare personnel. Open Forum Infect Dis 2: ofu115. https://doi.org/10.1093/ofid/ofu115 PMID: 25884004
20. Couch RB, Atmar RL, Franco LM, Quarles JM, Wells J, Arden N, et al. (2013) Antibody Correlates and Predictors of Immunity to Naturally Occurring Influenza in Humans and the Importance of Antibody to the Neuraminidase. Journal of Infectious Diseases 207: 974–981. https://doi.org/10.1093/infdis/jis935 PMID: 23307936
21. Salzberg S (2008) The contents of the syringe. Nature 454: 160–161. https://doi.org/10.1038/454160a PMID: 18615063
22. Shih AC, Hsiao TC, Ho MS, Li WH (2007) Simultaneous amino acid substitutions at antigenic sites drive influenza A hemagglutinin evolution. Proc Natl Acad Sci U S A 104: 6283–6288. https://doi.org/10.1073/pnas.0701396104 PMID: 17395716
23. Petrie JG, Parkhouse K, Ohmit SE, Malosh RE, Monto AS, Hensley SE (2016) Antibodies Against the Current Influenza A(H1N1) Vaccine Strain Do Not Protect Some Individuals From Infection With Contemporary Circulating Influenza A(H1N1) Virus Strains. J Infect Dis 214: 1947–1951. https://doi.org/10.1093/infdis/jiw479 PMID: 27923954
24. Osterholm MT, Kelley NS, Sommer A, Belongia EA (2012) Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 12: 36–44. https://doi.org/10.1016/ S1473-3099(11)70295-X PMID: 22032844
25. Davlin SL, Blanton L, Kniss K, Mustaquim D, Smith S, Kramer N, et al. (2016) Influenza Activity—United States, 2015–16 Season and Composition of the 2016–17 Influenza Vaccine. CDC. 567–575 p.
26. DeDiego ML, Anderson CS, Yang H, Holden-Wiltse J, Fitzgerald T, Treanor JJ, et al. (2016) Directed selection of influenza virus produces antigenic variants that match circulating human virus isolates and escape from vaccine-mediated immune protection. Immunology 148: 160–173. https://doi.org/10.1111/imm.12594 PMID: 26854888
27. Baker SF, Nogales A, Santiago FW, Topham DJ, Martinez-Sobrido L (2015) Competitive detection of influenza neutralizing antibodies using a novel bivalent fluorescence-based microneutralization assay (BiFMA). Vaccine 33: 3562–3570. https://doi.org/10.1016/j.vaccine.2015.05.049 PMID: 26044496
28. Baker SF, Guo H, Albrecht RA, Garcia-Sastre A, Topham DJ, Martinez-Sobrido L (2013) Protection against lethal influenza with a viral mimic. J Virol 87: 8591–8605. https://doi.org/10.1128/JVI.01081-13 PMID: 23720727
29. DeDiego ML, Nogales A, Lambert-Emo K, Martinez-Sobrido L, Topham DJ (2016) NS1 Protein Mutation I64T Affects Interferon Responses and Virulence of Circulating H3N2 Human Influenza A Viruses. J Virol 90: 9693–9711. https://doi.org/10.1128/JVI.01039-16 PMID: 27535054
30. Nogales A, Martinez-Sobrido L, Topham DJ, DeDiego ML (2016) NS1 protein amino acid changes D189N and V194I affect interferon responses, thermosensitivity and virulence of circulating H3N2 human influenza A viruses. J Virol.
31. Quinlivan M, Zamarin D, Garcia-Sastre A, Cullinane A, Chambers T, Palese P (2005) Attenuation of equine influenza viruses through truncations of the NS1 protein. J Virol 79: 8431–8439. https://doi.org/10.1128/JVI.79.13.8431-8439.2005 PMID: 15956587
32. Marsh GA, Hatami R, Palese P (2007) Specific residues of the influenza A virus hemagglutinin viral RNA are important for efficient packaging into budding Virions. Journal of Virology 81: 9727–9736. https://doi.org/10.1128/JVI.01144-07 PMID: 17634232
33. Krammer F, Margine I, Tan GS, Pica N, Krause JC, Palese P (2012) A carboxy-terminal trimerization domain stabilizes conformational epitopes on the stalk domain of soluble recombinant hemagglutinin substrates. PLoS One 7: e43603. https://doi.org/10.1371/journal.pone.0043603 PMID: 22928001
34. Wang J, Hilchey SP, Hyrien O, Huertas N, Perry S, Ramanunninair M, et al. (2015) Multi-Dimensional Measurement of Antibody-Mediated Heterosubtypic Immunity to Influenza. PLoS One 10: e0129858. https://doi.org/10.1371/journal.pone.0129858 PMID: 26103163
35. Lambre CR, Terzidis H, Greffard A, Webster RG (1990) Measurement of anti-influenza neuraminidase antibody using a peroxidase-linked lectin and microtitre plates coated with natural substrates. J Immunol Methods 135: 49–57. PMID: 1703190
36. Couzens L, Gao J, Westgeest K, Sandbulte M, Lugovtsev V, Fouchier R, et al. (2014) An optimized enzyme-linked lectin assay to measure influenza A virus neuraminidase inhibition antibody titers in human sera. J Virol Methods 210: 7–14. https://doi.org/10.1016/j.jviromet.2014.09.003 PMID: 25233882
37. Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32: 1792–1797. https://doi.org/10.1093/nar/gkh340 PMID: 15034147
38. Edgar RC (2004) MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5: 113. https://doi.org/10.1186/1471-2105-5-113 PMID: 15318951
39. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, et al. (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23: 2947–2948. https://doi.org/10.1093/bioinformatics/ btm404 PMID: 17846036
40. Kosakovsky Pond SL, Frost SD (2005) Not so different after all: a comparison of methods for detecting amino acid sites under selection. Mol Biol Evol 22: 1208–1222. https://doi.org/10.1093/molbev/msi105 PMID: 15703242
41. Pond SLK, Poon AFY, Frost SDW, editors (2007) Estimating selection pressures on alignments of coding sequences: Analyses using HyPhy. 81 p.
42. Anderson CS, DeDiego ML, Thakar J, Topham DJ (2016) Novel Sequence-Based Mapping of Recently Emerging H5NX Influenza Viruses Reveals Pandemic Vaccine Candidates. PLoS One 11: e0160510. https://doi.org/10.1371/journal.pone.0160510 PMID: 27494186
43. Kilbourne ED, Johansson BE, Grajower B (1990) Independent and disparate evolution in nature of influenza A virus hemagglutinin and neuraminidase glycoproteins. Proc Natl Acad Sci U S A 87: 786–790. PMID: 2300562
44. Laver WG, Air GM, Webster RG, Markoff LJ (1982) Amino acid sequence changes in antigenic variants of type A influenza virus N2 neuraminidase. Virology 122: 450–460. PMID: 6183823
45. Appiah GD, Blanton L, D’Mello T, Kniss K, Smith S, Mustaquim D, et al. (2015) Influenza Activity—United States, 2014–15 Season and Composition of the 2015–16 Influenza Vaccine. CDC. 583–590 p.
46. Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, et al. (2009) Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science 325: 197–201. https://doi.org/10.1126/science.1176225 PMID: 19465683
47. Xu R, Ekiert DC, Krause JC, Hai R, Crowe JE Jr., Wilson IA (2010) Structural basis of preexisting immunity to the 2009 H1N1 pandemic influenza virus. Science 328: 357–360. https://doi.org/10.1126/science.1186430 PMID: 20339031
48. Xu R, McBride R, Nycholat CM, Paulson JC, Wilson IA (2012) Structural characterization of the hemagglutinin receptor specificity from the 2009 H1N1 influenza pandemic. J Virol 86: 982–990. https://doi.org/10.1128/JVI.06322-11 PMID: 22072785
49. Burke DF, Smith DJ (2014) A recommended numbering scheme for influenza A HA subtypes. PLoS One 9: e112302. https://doi.org/10.1371/journal.pone.0112302 PMID: 25391151
50. Li Q, Qi J, Zhang W, Vavricka CJ, Shi Y, Wei J, et al. (2010) The 2009 pandemic H1N1 neuraminidase N1 lacks the 150-cavity in its active site. Nat Struct Mol Biol 17: 1266–1268. https://doi.org/10.1038/nsmb.1909 PMID: 20852645
51. Lu X, Liu F, Zeng H, Sheu T, Achenbach JE, Veguilla V, et al. (2014) Evaluation of the antigenic relatedness and cross-protective immunity of the neuraminidase between human influenza A (H1N1) virus and highly pathogenic avian influenza A (H5N1) virus. Virology 454–455: 169–175. https://doi.org/10.1016/j.virol.2014.02.011 PMID: 24725943
52. Han X, Bushweller JH, Cafiso DS, Tamm LK (2001) Membrane structure and fusion-triggering conformational change of the fusion domain from influenza hemagglutinin. Nat Struct Biol 8: 715–720. https://doi.org/10.1038/90434 PMID: 11473264
53. Gambaryan AS, Matrosovich MN (2015) What adaptive changes in hemagglutinin and neuraminidase are necessary for emergence of pandemic influenza virus from its avian precursor? Biochemistry (Mosc) 80: 872–880.
54. Meyer AG, Dawson ET, Wilke CO (2013) Cross-species comparison of site-specific evolutionary-rate variation in influenza haemagglutinin. Philos Trans R Soc Lond B Biol Sci 368: 20120334. https://doi.org/10.1098/rstb.2012.0334 PMID: 23382434
55. Meyer AG, Wilke CO (2015) Geometric Constraints Dominate the Antigenic Evolution of Influenza H3N2 Hemagglutinin. PLoS Pathog 11: e1004940.
56. Suzuki Y, Gojobori T (1999) A method for detecting positive selection at single amino acid sites. Mol Biol Evol 16: 1315–1328. PMID: 10563013
57. Nielsen R, Yang Z (1998) Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. Genetics 148: 929–936. PMID: 9539414
58. Lee AJ, Das SR, Wang W, Fitzgerald T, Pickett BE, Aevermann BD, et al. (2015) Diversifying Selection Analysis Predicts Antigenic Evolution of 2009 Pandemic H1N1 Influenza A Virus in Humans. J Virol 89: 5427–5440. https://doi.org/10.1128/JVI.03636-14 PMID: 25741011
59. Su YC, Bahl J, Joseph U, Butt KM, Peck HA, Koay ES, et al. (2015) Phylodynamics of H1N1/2009 influenza reveals the transition from host adaptation to immune-driven selection. Nat Commun 6: 7952. https://doi.org/10.1038/ncomms8952 PMID: 26245473
60. Komissarov A, Fadeev A, Sergeeva M, Petrov S, Sintsova K, Egorova A, et al. (2016) Rapid spread of influenza A(H1N1)pdm09 viruses with a new set of specific mutations in the internal genes in the beginning of 2015/2016 epidemic season in Moscow and Saint Petersburg (Russian Federation). Influenza Other Respir Viruses 10: 247–253. https://doi.org/10.1111/irv.12389 PMID: 26992820
61. Virelizier JL (1975) Host defenses against influenza virus: the role of anti-hemagglutinin antibody. J Immunol 115: 434–439. PMID: 807637
62. Ohmit SE, Petrie JG, Cross RT, Johnson E, Monto AS (2011) Influenza hemagglutination-inhibition antibody titer as a correlate of vaccine-induced protection. J Infect Dis 204: 1879–1885. https://doi.org/10.1093/infdis/jir661 PMID: 21998477
63. Hobson D, Curry RL, Beare AS, Ward-Gardner A (1972) The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J Hyg (Lond) 70: 767–777.
64. Henry C, Palm AE, Krammer F, Wilson PC (2017) From Original Antigenic Sin to the Universal Influenza Virus Vaccine. Trends Immunol.
65. Pica N, Hai R, Krammer F, Wang TT, Maamary J, Eggink D, et al. (2012) Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses. Proceedings of the National Academy of Sciences of the United States of America 109: 2573–2578. https://doi.org/10.1073/pnas.1200039109 PMID: 22308500
66. Thomson CA, Wang Y, Jackson LM, Olson M, Wang W, Liavonchanka A, et al. (2012) Pandemic H1N1 influenza infection and vaccination in humans induces cross-protective antibodies that target the hemagglutinin stem. Frontiers in Immunology 3.
67. Sui J, Hwang WC, Perez S, Wei G, Aird D, Chen LM, et al. (2009) Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol 16: 265–273. https://doi.org/10.1038/nsmb.1566 PMID: 19234466
68. Johansson BE, Kilbourne ED (1993) Dissociation of Influenza-Virus Hemagglutinin and Neuraminidase Eliminates Their Intravirionic Antigenic-Competition. Journal of Virology 67: 5721–5723. PMID: 8371337
69. Kosik I, Yewdell JW (2017) Influenza A virus hemagglutinin specific antibodies interfere with virion neuraminidase activity via two distinct mechanisms. Virology 500: 178–183. https://doi.org/10.1016/j.virol.2016.10.024 PMID: 27825034
70. Stohr K, Bucher D, Colgate T, Wood J (2012) Influenza virus surveillance, vaccine strain selection, and manufacture. Methods Mol Biol 865: 147–162. https://doi.org/10.1007/978-1-61779-621-0_9 PMID: 22528158
71. Li Y, Myers JL, Bostick DL, Sullivan CB, Madara J, Linderman SL, et al. (2013) Immune history shapes specificity of pandemic H1N1 influenza antibody responses. J Exp Med 210: 1493–1500. https://doi.org/10.1084/jem.20130212 PMID: 23857983
72. Linderman SL, Chambers BS, Zost SJ, Parkhouse K, Li Y, Herrmann C, et al. (2014) Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013–2014 influenza season. Proceedings of the National Academy of Sciences of the United States of America 111: 15798–15803. https://doi.org/10.1073/pnas.1409171111 PMID: 25331901
73. Katz J, Shu Y, McCauley J, Subbarao K, Webby R, Odagiri T, et al. (2017) Recommended composition of influenza virus vaccines for use in the 2017–2018 northern hemisphere influenza season. World Health Organization. 7 p.
74. Nicholls JM, Chan RW, Russell RJ, Air GM, Peiris JS (2008) Evolving complexities of influenza virus and its receptors. Trends Microbiol 16: 149–157. https://doi.org/10.1016/j.tim.2008.01.008 PMID: 18375125
75. Couch RB, Kasel JA, Gerin JL, Schulman JL, Kilbourne ED (1974) Induction of partial immunity to influenza by a neuraminidase-specific vaccine. J Infect Dis 129: 411–420. PMID: 4593871
76. Monto AS, Petrie JG, Cross RT, Johnson E, Liu M, Zhong WM, et al. (2015) Antibody to Influenza Virus Neuraminidase: An Independent Correlate of Protection. Journal of Infectious Diseases 212: 1191–1199. https://doi.org/10.1093/infdis/jiv195 PMID: 25858957
77. Das SR, Hensley SE, David A, Schmidt L, Gibbs JS, Puigbo P, et al. (2011) Fitness costs limit influenza A virus hemagglutinin glycosylation as an immune evasion strategy. Proceedings of the National Academy of Sciences of the United States of America 108: E1417–E1422. https://doi.org/10.1073/pnas. 1108754108 PMID: 22106257
78. Myers JL, Wetzel KS, Linderman SL, Li Y, Sullivan CB, Hensley SE (2013) Compensatory Hemagglutinin Mutations Alter Antigenic Properties of Influenza Viruses. Journal of Virology 87: 11168–11172. https://doi.org/10.1128/JVI.01414-13 PMID: 23926344
79. Hensley SE, Das SR, Bailey AL, Schmidt LM, Hickman HD, Jayaraman A, et al. (2009) Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift. Science 326: 734–736. https://doi.org/10.1126/science.1178258 PMID: 19900932
80. Xu R, Zhu X, McBride R, Nycholat CM, Yu W, Paulson JC, et al. (2012) Functional balance of the hemagglutinin and neuraminidase activities accompanies the emergence of the 2009 H1N1 influenza pandemic. J Virol 86: 9221–9232. https://doi.org/10.1128/JVI.00697-12 PMID: 22718832
81. Gaymard A, Le Briand N, Frobert E, Lina B, Escuret V (2016) Functional balance between neuraminidase and haemagglutinin in influenza viruses. Clin Microbiol Infect 22: 975–983. https://doi.org/10.1016/j.cmi.2016.07.007 PMID: 27424943
82. Hensley SE, Das SR, Gibbs JS, Bailey AL, Schmidt LM, Bennink JR, et al. (2011) Influenza A Virus Hemagglutinin Antibody Escape Promotes Neuraminidase Antigenic Variation and Drug Resistance. Plos One 6.
83. Skehel JJ, Stevens DJ, Daniels RS, Douglas AR, Knossow M, Wilson IA, et al. (1984) A carbohydrate side chain on hemagglutinins of Hong Kong influenza viruses inhibits recognition by a monoclonal antibody. Proc Natl Acad Sci U S A 81: 1779–1783. PMID: 6584912
84. Anderson CS, Ortega S, Chaves FA, Clark AM, Yang H, Topham DJ, et al. (2017) Natural and directed antigenic drift of the H1 influenza virus hemagglutinin stalk domain. Scientific Reports https://doi.org/10.1038/s41598-017-14931-7 PMID: 29097696
85. Tan GS, Krammer F, Eggink D, Kongchanagul A, Moran TM, Palese P (2012) A pan-H1 anti-hemagglutinin monoclonal antibody with potent broad-spectrum efficacy in vivo. J Virol 86: 6179–6188. https://doi.org/10.1128/JVI.00469-12 PMID: 22491456
86. Krammer F, Pica N, Hai R, Tan GS, Palese P (2012) Hemagglutinin Stalk-Reactive Antibodies Are Boosted following Sequential Infection with Seasonal and Pandemic H1N1 Influenza Virus in Mice. J Virol 86: 10302–10307. https://doi.org/10.1128/JVI.01336-12 PMID: 22787225
87. Thomson CA, Wang Y, Jackson LM, Olson M, Wang W, Liavonchanka A, et al. (2012) Pandemic H1N1 Influenza Infection and Vaccination in Humans Induces Cross-Protective Antibodies that Target the Hemagglutinin Stem. Front Immunol 3: 87. https://doi.org/10.3389/fimmu.2012.00087 PMID: 22586427
88. Chai N, Swem LR, Reichelt M, Chen-Harris H, Luis E, Park S, et al. (2016) Two Escape Mechanisms of Influenza A Virus to a Broadly Neutralizing Stalk-Binding Antibody. PLoS Pathog 12: e1005702. https://doi.org/10.1371/journal.ppat.1005702 PMID: 27351973