In the shadow of hemagglutinin: A growing interest in influenza viral neuraminidase and its role as a vaccine antigen

Viruses

Volumn 6, Issue 6, 2014, Pages 2465-2494

  Wohlbold, Teddy John ^a   Krammer, Florian ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Cross protection; Influenza virus; Influenza virus vaccine; Neuraminidase; Sialidase; Universal influenza virus vaccine

Indexed keywords

AMANTADINE; DNA VACCINE; INFLUENZA VACCINE; LATENCY ASSOCIATED PEPTIDE; MONOCLONAL ANTIBODY; MUCIN; OSELTAMIVIR; PLACEBO; RIMANTADINE; TRANSFORMING GROWTH FACTOR BETA; TRIPLE VACCINE; UNCLASSIFIED DRUG; VIRUS HEMAGGLUTININ; VIRUS LIKE PARTICLE VACCINE; VIRUS SIALIDASE; X 32; X 42; ZANAMIVIR; INFLUENZA VIRUS HEMAGGLUTININ; NA PROTEIN, INFLUENZA A VIRUS; SIALIDASE; VIRUS ANTIGEN; VIRUS PROTEIN;

AMINO ACID SEQUENCE; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; COMPLEMENT DEPENDENT CYTOTOXICITY; CROSS PROTECTION; DISEASE SEVERITY; DOMINANCE BEHAVIOR; DRUG DESIGN; DRUG TARGETING; ELECTRON MICROSCOPY; ENZYME ACTIVITY; ENZYME STRUCTURE; EVOLUTION; HETEROLOGOUS IMMUNITY; HUMAN; HUMORAL IMMUNITY; IMMUNE RESPONSE; IMMUNOGENICITY; INFLUENZA; INFLUENZA VIRUS; INFLUENZA VIRUS A H1N1; INFLUENZA VIRUS A H5N1; INFLUENZA VIRUS B; INFLUENZA VIRUS C; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHYLOGENETIC TREE; PROTEIN FUNCTION; PROTEIN SYNTHESIS INHIBITION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SEROCONVERSION; VACCINATION; VIROLOGY; VIRUS INHIBITION; VIRUS SHEDDING; ANIMAL; CHEMISTRY; IMMUNOLOGY; INFLUENZA VIRUS A; INFLUENZA, HUMAN; METABOLISM;

ANIMALS; ANTIGENS, VIRAL; HEMAGGLUTININ GLYCOPROTEINS, INFLUENZA VIRUS; HUMANS; INFLUENZA A VIRUS; INFLUENZA VACCINES; INFLUENZA, HUMAN; NEURAMINIDASE; VIRAL PROTEINS;

EID: 84903131264     PISSN: 19994915     EISSN: None     Source Type: Journal    
DOI: 10.3390/v6062465     Document Type: Review

References (115)

1. Pappas, G.; Kiriaze, I.J.; Falagas, M. E. Insights into infectious disease in the era of Hippocrates. Int. J. Infect. Dis. 2008, 12, 347-350.
2. Johnson, N.P.; Mueller, J. Updating the accounts: Global mortality of the 1918-1920-Spanish{norm of matrix} influenza pandemic. Bull. Hist. Med. 2002, 76, 105-115.
3. Wright, P.F.; Neumann, G.; Kawaoka, Y. Orthomyxoviruses. Fields Virol. 2013, 2, 1693-1740.
4. The World Health Organization. Influenza (Seasonal): Fact Sheet No. 211; The World Health Organization: Geneva, Switzerland, 2009.
5. Molinari, N.A.; Ortega-Sanchez, I.R.; Messonnier, M.L.; Thompson, W.W.; Wortley, P.M.; Weintraub, E.; Bridges, C.B. The annual impact of seasonal influenza in the US: Measuring disease burden and costs. Vaccine 2007, 25, 5086-5096.
6. Shaw, M.; Palese, P. Orthomyxoviridae: The Viruses and Their Replication. Fields Virol. 2013, 2, 1648-1689.
7. CDC. Types of Influenza Viruses{pipe}Seasonal Influenza (Flu); Centers for Disease Control and Prevention: Atlanta, GA, USA, 2013.
8. CDC. Seasonal Influenza (Flu)-Weekly Report: Influenza Summary Update; Centers for Disease Control and Prevention: Atlanta, GA, USA, 2013.
9. Tong, S.; Zhu, X.; Li, Y.; Shi, M.; Zhang, J.; Bourgeois, M.; Yang, H.; Chen, X.; Recuenco, S.; Gomez, J.; et al. New world bats harbor diverse influenza a viruses. PLoS Pathog. 2013, 9, e1003657.
10. Arzey, G.G.; Kirkland, P.D.; Arzey, K.E.; Frost, M.; Maywood, P.; Conaty, S.; Hurt, A.C.; Deng, Y.; Barr, I.; Dwyer, D.E.; et al. Influenza Virus A (H10N7) in Chickens and Poultry Abattoir Workers, Australia. Emerg. Infect. Dis. 2012, 18, 814-816.
11. Beare, A.S.; Webster, R.G. Replication of avian influenza viruses in humans. Arch. Virol. 1991, 119, 37-42.
12. CDC Update: Influenza Activity-United States and Worldwide, 2002-2003 Season, and Composition of the 2003-2004 Influenza Vaccine. Available online: http://www.cdc.gov/mmwr/ preview/mmwrhtml/mm5222a2.htm/ (accessed on 6 January 2013).
13. Johansson, B.E.; Cox, M.M.J. Influenza viral neuraminidase: The forgotten antigen. Expert Rev. Vaccines 2011, 10, 1683-1695.
14. Kayali, G.; Ortiz, E.J.; Chorazy, M.L.; Gray, G.C. Evidence of previous avian influenza infection among US turkey workers. Zoonoses Public Health 2010, 57, 265-272.
15. Kayali, G.; Barbour, E.; Dbaibo, G.; Tabet, C.; Saade, M.; Shaib, H. A; Debeauchamp, J.; Webby, R.J. Evidence of infection with H4 and H11 avian influenza viruses among Lebanese chicken growers. PLoS One 2011, 6, e26818.
16. WHO/CDS/CSR/RMD EID Weekly Updates: Emerging and Reemerging Infectious Diseases, Region of the Americas. Available online: http://www1.paho.org/English/AD/DPC/CD/eid-eer-07-may-2004.htm#birdflu/ (accessed on 18 November 2013).
17. Yuan, J.; Zhang, L.; Kan, X.; Jiang, L.; Yang, J.; Guo, Z.; Ren, Q. Origin and molecular characteristics of a novel 2013 avian influenza A(H6N1) virus causing human infection in Taiwan. Clin. Infect. Dis. 2013, 57, 1367-1368.
18. Chen, H.; Yuan, H.; Gao, R.; Zhang, J.; Wang, D.; Xiong, Y.; Fan, G.; Yang, F.; Li, X.; Zhou, J. Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: A descriptive study. Lancet 2014, 383, 714-721.
19. Pica, N.; Palese, P. Toward a universal influenza virus vaccine: Prospects and challenges. Annu. Rev. Med. 2013, 64, 189-202.
20. Zachary, K.C. Treatment of Seasonal Influenza in Adults. Available online: http://www. uptodate.com/contents/treatment-of-seasonal-influenza-in-adults?detectedLanguage=en&source= search_result&search=influenza&selectedTitle=1%7E150&provider=noProvider#H13/ (accessed on 18 November 2013).
21. Krammer, F.; Grabherr, R. Alternative influenza vaccines made by insect cells. Trends Mol. Med. 2010, 16, 313-320.
22. Dormitzer, P.R.; Tsai, T.F.; del Giudice, G. New technologies for influenza vaccines. Hum. Vaccines Immunother. 2012, 8, 45-58.
23. Quan, F.-S.; Huang, C.; Compans, R.W.; Kang, S.-M. Virus-like particle vaccine induces protective immunity against homologous and heterologous strains of influenza virus. J. Virol. 2007, 81, 3514-3524.
24. Klausberger, M.; Wilde, M.; Palmberger, D.; Hai, R.; Albrecht, R.A.; Margine, I.; Hirsh, A.; García-Sastre, A.; Grabherr, R.; Krammer, F. One-shot vaccination with an insect cell-derived low-dose influenza A H7 virus-like particle preparation protects mice against H7N9 challenge. Vaccine 2014, 32, 355-362.
25. Krammer, F.; Palese, P. Influenza virus hemagglutinin stalk-based antibodies and vaccines. Curr. Opin. Virol. 2013, 3, 521-530.
26. Gerhard, W.; Yewdell, J.; Frankel, M.E.; Webster, R. Antigenic structure of influenza virus haemagglutinin defined by hybridoma antibodies. Nature 1981, 290, 713-716.
27. Hensley, S.E.; Das, S.R.; Bailey, A.L.; Schmidt, L.M.; Hickman, H.D.; Jayaraman, A.; Viswanathan, K.; Raman, R.; Sasisekharan, R.; Bennink, J.R.; et al. Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift. Science 2009, 326, 734-736.
28. Marcelin, G.; Sandbulte, M.R.; Webby, R.J. Contribution of antibody production against neuraminidase to the protection afforded by influenza vaccines. Rev. Med. Virol. 2012, 22, 267-279.
29. Eichelberger, M.; Golding, H.; Hess, M.; Weir, J.; Subbarao, K.; Luke, C.J.; Friede, M.; Wood, D. FDA/NIH/WHO public workshop on immune correlates of protection against influenza A viruses in support of pandemic vaccine development, Bethesda, Maryland, US, December 10-11, 2007. Vaccine 2008, 26, 4299-4303.
30. Bright, R.A.; Neuzil, K.M.; Pervikov, Y.; Palkonyay, L. WHO meeting on the role of neuraminidase in inducing protective immunity against influenza infection, Vilamoura, Portugal, September 14, 2008. Vaccine 2009, 27, 6366-6369.
31. Hirst, G.K. The quantitiative determination of influenza virus and antibodies by means of red cell agglutination. J. Exp. Med. 1942, 75, 49-64.
32. Burnet, M. quoted in. Aust. J. Exp. Biol. Med. Sci. 1948, 26, 410.
33. Seto, J.T.; Drzeniek, R.; Rott, R. Isolation of a low molecular weight sialidase (neuraminidase) from influenza virus. Biochim. Biophys. Acta Enzymol. Biol. Oxid. 1966, 113, 402-404.
34. Varghese, J.N.; Laver, W.G.; Colman, P.M. Structure of the influenza virus glycoprotein antigen neuraminidase at 2.9 A resolution. Nature 1983, 303, 35-40.
35. Wilson, I.A.; Skehel, J.J.; Wiley, D.C. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 [angst] resolution. Nature 1981, 289, 366-373.
36. Palese, P.; Schulman, J.L.; Bodo, G.; Meindl, P. Inhibition of influenza and parainfluenza virus replication in tissue culture by 2-deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid (FANA). Virology 1974, 59, 490-498.
37. Von Itzstein, M.; Wu, W.-Y.; Kok, G.B.; Pegg, M.S.; Dyason, J.C.; Jin, B.; Phan, T.V.; Smythe, M.L.; White, H.F.; Oliver, S.W.; et al. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 1993, 363, 418-423.
38. Air, G.M. Influenza neuraminidase. Influ. Respir. Viruses 2012, 6, 245-256.
39. Xu, X.; Zhu, X.; Dwek, R.A.; Stevens, J.; Wilson, I.A. Structural characterization of the 1918 influenza virus H1N1 neuraminidase. J. Virol. 2008, 82, 10493-10501.
40. Zhu, X.; McBride, R.; Nycholat, C.M.; Yu, W.; Paulson, J.C.; Wilson, I.A. Influenza virus neuraminidases with reduced enzymatic activity that avidly bind sialic Acid receptors. J. Virol. 2012, 86, 13371-13383.
41. Paterson, R.G.; Lamb, R.A. Conversion of a class II integral membrane protein into a soluble and efficiently secreted protein: Multiple intracellular and extracellular oligomeric and conformational forms. J. Cell Biol. 1990, 110, 999-1011.
42. Bucher, D.J.; Kilbourne, E.D. A 2 (N2) neuraminidase of the X-7 influenza virus recombinant: Determination of molecular size and subunit composition of the active unit. J. Virol. 1972, 10, 60-66.
43. Technical Note: R&D Systems Structural Characterization of the 1918 Influenza Virus Neuraminidase. Available online: http://www.rndsystems.com/cb_detail_objectname_cb09i2_ technical_notes.aspx/(accessed on 10 November 2013).
44. Sylte, M.J.; Suarez, D.L. Influenza neuraminidase as a vaccine antigen. Curr. Top. Microbiol. Immunol. 2009, 333, 227-241.
45. Laver, G.; Potter, C.W. Influenza virus surface glycoproteins, haemagglutinin and neuraminidase: A personal account. In Perspectives in Medical Virology; Elsevier: Amsterdam, The Netherlands, 2002; Volume 7, pp. 31-47.
46. Doyle, T.M.; Hashem, A.M.; Li, C.; van Domselaar, G.; Larocque, L.; Wang, J.; Smith, D.; Cyr, T.; Farnsworth, A.; He, R.; et al. Universal anti-neuraminidase antibody inhibiting all influenza A subtypes. Antivir. Res. 2013, 100, 567-574.
47. Doyle, T.M.; Li, C.; Bucher, D.J.; Hashem, A.M.; van Domselaar, G.; Wang, J.; Farnsworth, A.; She, Y.-M.; Cyr, T.; He, R.; et al. A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug resistant strains. Biochem. Biophys. Res. Commun. 2013, 441, 226-229.
48. Wan, H.; Gao, J.; Xu, K.; Chen, H.; Couzens, L.K.; Rivers, K.H.; Easterbrook, J.D.; Yang, K.; Zhong, L.; Rajabi, M.; et al. Molecular basis for broad neuraminidase immunity: Conserved epitopes in seasonal and pandemic H1N1 as well as H5N1 influenza viruses. J. Virol. 2013, 87, 9290-9300.
49. Palese, P.; Tobita, K.; Ueda, M.; Compans, R.W. Characterization of temperature sensitive influenza virus mutants defective in neuraminidase. Virology 1974, 61, 397-410.
50. Hooper, K.A.; Bloom, J.D. A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein. J. Virol. 2013, doi:10.1128/JVI.01889-13.
51. Matrosovich, M.N.; Matrosovich, T.Y.; Roberts, N.A.; Klenk, H.; Gray, T. Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. 2004, 78, 12665-12667.
52. Cohen, M.; Zhang, X.-Q.; Senaati, H.P.; Chen, H.-W.; Varki, N.M.; Schooley, R.T.; Gagneux, P. Influenza A penetrates host mucus by cleaving sialic acids with neuraminidase. Virol. J. 2013, 10, 321.
53. Li, M.O.; Wan, Y.Y.; Sanjabi, S.; Robertson, A.-K.L.; Flavell, R.A. Transforming growth factor-beta regulation of immune responses. Annu. Rev. Immunol. 2006, 24, 99-146.
54. Barcellos-Hoff, M.H.; Dix, T.A. Redox-Mediated Activation of Latent Transforming Growth factor-beta1. Mol. Endocrinol. 1996, 10, 1077-1083.
55. Brown, P.; Wakefield, L.; Levinson, A.; Sporn, M. Physicochemical activation of recombinant latent transforming growth factor-beta's 1, 2, and 3. Growth Factors 1990, 3, 35-43.
56. Gantt, K.R.; Schultz-Cherry, S.; Rodriguez, N.; Jeronimo, S.M.B.; Nascimento, E.T.; Goldman, T.L.; Recker, T.J.; Miller, M.A.; Wilson, M.E. Activation of TGF-beta by Leishmania chagasi: Importance for parasite survival in macrophages. J. Immunol. 2003, 170, 2613-2620.
57. Schultz-Cherry, S.; Hinshaw, V.S. Influenza virus neuraminidase activates latent transforming growth factor beta. J. Virol. 1996, 70, 8624-8629.
58. Carlson, C.M.; Turpin, E.A.; Moser, L.A.; O'Brien, K.B.; Cline, T.D.; Jones, J.C.; Tumpey, T.M.; Katz, J.M.; Kelley, L.A.; Gauldie, J.; et al. Transforming growth factor-β: Activation by neuraminidase and role in highly pathogenic H5N1 influenza pathogenesis. PLoS Pathog. 2010, 6, e1001136.
59. Webster, R.G.; Brown, L.E.; Laver, W.G. Antigenic and biological characterization of influenza virus neuraminidase (N2) with monoclonal antibodies. Virology 1984, 135, 30-42.
60. Hurwitz, J.L.; Hackett, C.J.; Elizabeth, C.; Gerhard, W. Murine Th response to influenza virus: Recognition of hemagglutinin, neuraminidase, matrix, and nucleoproteins. J. Immunol. 1994, 134, 1994-1998.
61. Herrera, M.T.; Gonzalez, Y.; Juárez, E.; Hernández-Sánchez, F.; Carranza, C.; Sarabia, C.; Guzman-Beltran, S.; Manjarrez, M.E.; Muñoz-Torrico, M.; Garcia-Garcia, L.; et al. Humoral and cellular responses to a non-adjuvanted monovalent H1N1 pandemic influenza vaccine in hospital employees. BMC Infect. Dis. 2013, 13, 544.
62. Thomas, P.G.; Keating, R.; Hulse-Post, D.J.; Doherty, P.C. Cell-mediated protection in influenza infection. Emerg. Infect. Dis. 2006, 12, 48-54.
63. Johansson, B.E.; Moran, T.M.; Bona, C.A.; Popple, S.W.; Kilbourne, E.D. 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. 1987, 139, 2010-2014.
64. Kilbourne, E.D. Comparative efficacy of neuraminidase-specific and conventional influenza virus vaccines in induction of antibody to neuraminidase in humans. J. Infect. Dis. 1976, 134, 384-394.
65. Powers, D.C.; Kilbourne, E.D.; Johansson, B.E. Neuraminidase-specific antibody responses to inactivated influenza virus vaccine in young and elderly adults. Clin. Diagn. Lab. Immunol. 1996, 3, 511-516.
66. Couch, R.B.; Atmar, R.L.; Keitel, W.A.; Quarles, J.M.; Wells, J.; Arden, N.; Niño, D. Randomized comparative study of the serum antihemagglutinin and antineuraminidase antibody responses to six licensed trivalent influenza vaccines. Vaccine 2012, 31, 190-195.
67. Sultana, I.; Yang, K.; Getie-Kebtie, M.; Couzens, L.; Markoff, L.; Alterman, M.; Eichelberger, M.C. Stability of neuraminidase in inactivated influenza vaccines. Vaccine 2014, 32, 2225-2230.
68. Akram, A.; Inman, R.D. Immunodominance: A pivotal principle in host response to viral infections. Clin. Immunol. 2012, 143, 99-115.
69. Johansson, B.E.; Bucher, D.J.; Kilbourne, E.D. Purified influenza virus hemagglutinin and neuraminidase are equivalent in stimulation of antibody response but induce contrasting types of immunity to infection. J. Virol. 1989, 63, 1239-1246.
70. Lamb, R.A. The influenza virus RNA segments and their encoded proteins. In Genetics of Influenza Viruses; Palese, P., Kingsbury, D.M., Eds.; Springer-Verlag Wein: New York, NY, USA, 1983.
71. Johansson, B.E.; Moran, T.M.; Kilbourne, E.D. Antigen-presenting B cells and helper T cells cooperatively mediate intravirionic antigenic competition between influenza A virus surface glycoproteins. Proc. Natl. Acad. Sci. USA 1987, 84, 6869-6873.
72. Johansson, B.E.; Kilbourne, E.D. Dissociation of influenza virus hemagglutinin and neuraminidase eliminates their intravirionic antigenic competition. J. Virol. 1993, 67, 5721-5723.
73. Ogra, P.L.; Chow, T.; Beutner, K.R.; Rubi, E.; Strussenberg, J.; DeMello, S.; Rizzone, C. Clinical and immunologic evaluation of neuraminidase-specific influenza A virus vaccine in humans. J. Infect. Dis. 1977, 135, 499-506.
74. Krammer, F.; Palese, P. Universal influenza virus vaccines: Need for clinical trials. Nat. Immunol. 2014, 15, 3-5.
75. Margine, I.; Hai, R.; Albrecht, R.A.; Obermoser, G.; Harrod, A.C.; Banchereau, J.; Palucka, K.; García-Sastre, A.; Palese, P.; Treanor, J.J.; et al. H3N2 influenza virus infection induces broadly reactive hemagglutinin stalk antibodies in humans and mice. J. Virol. 2013, 87, 4728-4737.
76. Wang, T.T.; Tan, G.S.; Hai, R.; Pica, N.; Petersen, E.; Moran, T.M.; Palese, P. Broadly protective monoclonal antibodies against H3 influenza viruses following sequential immunization with different hemagglutinins. PLoS Pathog. 2010, 6, e1000796.
77. Wang, T.T.; Tan, G.S.; Hai, R.; Pica, N.; Ngai, L.; Ekiert, D.C.; Wilson, I.A.; García-Sastre, A.; Moran, T.M.; Palese, P. Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes. Proc. Natl. Acad. Sci. USA 2010, 107, 18979-18984.
78. Hai, R.; Krammer, F.; Tan, G.S.; Pica, N.; Eggink, D.; Maamary, J.; Margine, I.; Albrecht, R.A.; Palese, P. Influenza viruses expressing chimeric hemagglutinins: Globular head and stalk domains derived from different subtypes. J. Virol. 2012, 86, 5774-5781.
79. Krammer, F.; Pica, N.; Hai, R.; Margine, I.; Palese, P. Chimeric hemagglutinin influenza virus vaccine constructs elicit broadly protective stalk-specific antibodies. J. Virol. 2013, 87, 6542-6550.
80. Krammer, F.; Pica, N.; Hai, R.; Tan, G.S.; Palese, P. Hemagglutinin stalk-reactive antibodies are boosted following sequential infection with seasonal and pandemic H1N1 influenza virus in mice. J. Virol. 2012, 86, 10302-10307.
81. Krammer, F.; Margine, I.; Hai, R.; Flood, A.; Hirsh, A.; Tsvetnitsky, V.; Chen, D.; Palese, P. H3 stalk-based chimeric hemagglutinin influenza virus constructs protect mice from H7N9 challenge. J. Virol. 2014, 88, 2340-2343.
82. Krammer, F.; Hai, R.; Yondola, M.; Tan, G.S.; Leyva-Grado, V.H.; Ryder, A.B.; Miller, M.S.; Rose, J.K.; Palese, P.; García-Sastre, A.; et al. Assessment of influenza virus hemagglutinin stalk-based immunity in ferrets. J. Virol. 2014, 88, 3432-3442.
83. Fritz, R.; Sabarth, N.; Kiermayr, S.; Hohenadl, C.; Howard, M.K.; Ilk, R.; Kistner, O.; Ehrlich, H.J.; Barrett, P.N.; Kreil, T.R. A vero cell-derived whole-virus H5N1 vaccine effectively induces neuraminidase-inhibiting antibodies. J. Infect. Dis. 2012, 205, 28-34.
84. Van der Velden, M.V.W.; Fritz, R.; Pöllabauer, E.M.; Portsmouth, D.; Howard, M.K.; Kreil, T.R.; Dvorak, T.; Fritsch, S.; Vesikari, T.; Diez-Domingo, J.; et al. Safety and immunogenicity of a vero cell culture-derived whole-virus influenza A(H5N1) vaccine in a pediatric population. J. Infect. Dis. 2014, 209, 12-23.
85. Fries, L.F.; Smith, G.E.; Glenn, G.M. A recombinant viruslike particle influenza A (H7N9) vaccine. N. Engl. J. Med. 2013, 369, 2564-2566.
86. Schulman, J.L.; Khakpour, M.; Kilbourne, E. Protective effects of specific immunity to viral neuraminidase on influenza virus infection in mice. J. Virol. 1968, 2, 778-776.
87. Rott, R.; Becht, H.; Orlich, M. The significance of influenza virus neuraminidase in immunity. J. Gen. Virol. 1974, 22, 35-41.
88. Monto, A.S.; Kendal, A.P. Effect of neuraminidase antibody on Hong Kong influenza. Lancet 1973, 1, 623-625.
89. Couch, R.B.; Kasel, J.A.; Gerin, J.L.; Schulman, J.L.; Kilbourne, E.D.; Lanier, W.S.; Warden, A.; Taylor, B. Induction of partial immunity to influenza by a neuraminidase-specific vaccine. J. Infect. Dis. 1974, 129, 411-420.
90. Palese, P.; Wang, T.T. Why do influenza virus subtypes die out? A hypothesis. mBio 2011, 2, doi:10.1128/mBio.00150-11.
91. Abed, Y.; Hardy, I.; Li, Y.; Boivin, G. Divergent evolution of hemagglutinin and neuraminidase genes in recent influenza A:H3N2 viruses isolated in Canada. J. Med. Virol. 2002, 67, 589-595.
92. Kilbourne, E.D.; Johansson, B.E.; Grajower, B. Independent and disparate evolution in nature of influenza A virus hemagglutinin and neuraminidase glycoproteins. Proc. Natl. Acad. Sci. USA 1990, 87, 786-790.
93. Venkatramani, L.; Bochkareva, E.; Lee, J.T.; Gulati, U.; Graeme Laver, W.; Bochkarev, A.; Air, G.M. An epidemiologically significant epitope of a 1998 human influenza virus neuraminidase forms a highly hydrated interface in the NA-antibody complex. J. Mol. Biol. 2006, 356, 651-663.
94. Xu, J.; Davis, C.T.; Christman, M.C.; Rivailler, P.; Zhong, H.; Donis, R.O.; Lu, G. Evolutionary history and phylodynamics of influenza A and B neuraminidase (NA) genes inferred from large-scale sequence analyses. PLoS One 2012, 7, e38665.
95. Johansson, B.E.; Pokorny, B.A.; Tiso, V.A. Supplementation of conventional trivalent influenza vaccine with purified viral N1 and N2 neuraminidases induces a balanced immune response without antigenic competition. Vaccine 2002, 20, 1670-1674.
96. Cate, T.R.; Rayford, Y.; Niño, D.; Winokur, P.; Brady, R.; Belshe, R.; Chen, W.; Atmar, R.L.; Couch, R.B. A high dosage influenza vaccine induced significantly more neuraminidase antibody than standard vaccine among elderly subjects. Vaccine 2010, 28, 2076-2079.
97. Yang, Y.-L.; Chang, S.-H.; Gong, X.; Wu, J.; Liu, B. Expression, purification and characterization of low-glycosylation influenza neuraminidase in α-1,6-mannosyltransferase defective Pichia pastoris. Mol. Biol. Rep. 2012, 39, 857-864.
98. Kilbourne, E.D.; Couch, R.B.; Kasel, J.A.; Keitel, W.A.; Cate, T.R.; Quarles, J.H.; Grajower, B.; Pokorny, B.A.; Johansson, B.E. Purified influenza A virus N2 neuraminidase vaccine is immunogenic and non-toxic in humans. Vaccine 1995, 13, 1799-1803.
99. Hocart, M.; Grajower, B.; Donabedian, A.; Pokorny, B.; Whitaker, C.; Kilbourne, E.D. Preparation and characterization of a purified influenza virus neuraminidase vaccine. Vaccine 1995, 13, 1793-1798.
100. Martinet, W.; Saelens, X.; Deroo, T.; Neirynck, S.; Contreras, R.; Min Jou, W.; Fiers, W. Protection of mice against a lethal influenza challenge by immunization with yeast-derived recombinant influenza neuraminidase. Eur. J. Biochem. 1997, 247, 332-338.
101. Chen, Z.; Matsuo, K.; Asanuma, H.; Takahashi, H.; Iwasaki, T.; Suzuki, Y.; Alzawa, C.; Kurata, T.; Tamura, S. Enhanced protection against a lethal influenza virus challenge by immunization with both hemagglutinin-and neuraminidase-expressing DNAs. Vaccine 1999, 17, 653-659.
102. Chen, Z.; Kadowaki, S.; Hagiwara, Y.; Yoshikawa, T.; Matsuo, K.; Kurata, T.; Tamura, S. Cross-protection against a lethal influenza virus infection by DNA vaccine to neuraminidase. Vaccine 2000, 18, 3214-3222.
103. Bosch, B.J.; Bodewes, R.; de Vries, R.P.; Kreijtz, J.H.C.M.; Bartelink, W.; van Amerongen, G.; Rimmelzwaan, G.F.; de Haan, C.A.M.; Osterhaus, A.D.M.E.; Rottier, P.J.M. Recombinant soluble, multimeric HA and NA exhibit distinctive types of protection against pandemic swine-origin 2009 A(H1N1) influenza virus infection in ferrets. J. Virol. 2010, 84, 10366-10374.
104. Wu, C.-Y.; Yeh, Y.-C.; Chan, J.-T.; Yang, Y.-C.; Yang, J.-R.; Liu, M.-T.; Wu, H.-S.; Hsiao, P.-W. A VLP vaccine induces broad-spectrum cross-protective antibody immunity against H5N1 and H1N1 subtypes of influenza A virus. PLoS One 2012, 7, e42363.
105. Easterbrook, J.D.; Schwartzman, L.M.; Gao, J.; Kash, J.C.; Morens, D.M.; Couzens, L.; Wan, H.; Eichelberger, M.C.; Taubenberger, J.K. Protection against a lethal H5N1 influenza challenge by intranasal immunization with virus-like particles containing 2009 pandemic H1N1 neuraminidase in mice. Virology 2012, 432, 39-44.
106. Quan, F.-S.; Kim, M.-C.; Lee, B.-J.; Song, J.-M.; Compans, R.W.; Kang, S.-M. Influenza M1 VLPs containing neuraminidase induce heterosubtypic cross-protection. Virology 2012, 430, 127-135.
107. Rockman, S.; Brown, L.E.; Barr, I.G.; Gilbertson, B.; Lowther, S.; Kachurin, A.; Kachurina, O.; Klippel, J.; Bodle, J.; Pearse, M.; et al. Neuraminidase-inhibiting antibody is a correlate of cross-protection against lethal H5N1 influenza virus in ferrets immunized with seasonal influenza vaccine. J. Virol. 2013, 87, 3053-3061.
108. Sylte, M.J.; Hubby, B.; Suarez, D.L. Influenza neuraminidase antibodies provide partial protection for chickens against high pathogenic avian influenza infection. Vaccine 2007, 25, 3763-3772.
109. Marcelin, G.; Bland, H.M.; Negovetich, N.J.; Sandbulte, M.R.; Ellebedy, A.H.; Webb, A.D.; Griffin, Y.S.; DeBeauchamp, J.L.; McElhaney, J.E.; Webby, R.J. Inactivated seasonal influenza vaccines increase serum antibodies to the neuraminidase of pandemic influenza A(H1N1) 2009 virus in an age-dependent manner. J. Infect. Dis. 2010, 202, 1634-1638.
110. Marcelin, G.; DuBois, R.; Rubrum, A.; Russell, C.J.; McElhaney, J.E.; Webby, R.J. A contributing role for anti-neuraminidase antibodies on immunity to pandemic H1N1 2009 influenza A virus. PLoS One 2011, 6, e26335.
111. Xie, H.; Li, X.; Gao, J.; Lin, Z.; Jing, X.; Plant, E.; Zoueva, O.; Eichelberger, M.C.; Ye, Z. Revisiting the 1976-swine flue vaccine clinical trials: Cross-reactive hemagglutinin and neuraminidase antibodies and their role in protection against the 2009 H1N1 pandemic virus in mice. Clin. Infect. Dis. 2011, 53, 1179-1187.
112. Smith, D.J. Mapping the antigenic and genetic evolution of influenza virus. Science 2004, 305, 371-376.
113. Sandbulte, M.R.; Westgeest, K.B.; Gao, J.; Xu, X.; Klimov, A.I.; Russell, C.A.; Burke, D.F.; Smith, D.J.; Fouchier, R.A.M.; Eichelberger, M.C. Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses. Proc. Natl. Acad. Sci. USA 2011, 108, 20748-20753.
114. Van Reeth, K.; Braeckmans, D.; Cox, E.; van Borm, S.; van den Berg, T.; Goddeeris, B.; de Vleeschauwer, A. Prior infection with an H1N1 swine influenza virus partially protects pigs against a low pathogenic H5N1 avian influenza virus. Vaccine 2009, 27, 6330-6339.
115. Shoji, Y.; Chichester, J.A.; Palmer, G.A.; Farrance, C.E.; Stevens, R.; Stewart, M.; Goldschmidt, L.; Deyde, V.; Gubareva, L.; Klimov, A.; et al. An influenza N1 neuraminidase-specific monoclonal antibody with broad neuraminidase inhibition activity against H5N1 HPAI viruses. Hum. Vaccines 2011, 7, 199-204.