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The challenges of creating a universal influenza vaccine


Periodically emerging new influenza strains along with the lack of population immunity to these new viruses can lead to a pandemic, making influenza infection especially dangerous. The fragmented nature of the influenza virus genome contributes to the formation of influenza virus reassortants containing genomic fragments from different strains. This mechanism is one of the reasons for the existing influenza virus antigenic diversity in nature and the occurrence of influenza pandemics. Vaccination is the best measure to prevent the spread of influenza infection, however, the efficacy of existing vaccines is not sufficient, especially for the elderly and small children. Specific immunity developed after disease or immunization poorly protects against infection by influenza viruses of another subtype. In this regard, there is an urgent need for a more effective universal influenza vaccine that provides a long-lasting wide cross-protective immunity, and is able to resist to influenza A and B viruses of all known subtypes. Basic approaches and challenges in creating such a vaccine are discussed in this review.

About the Author

A. Y. Egorov
HSC Development Ltd

Andrej Egorov



1. Bhat N, Wright JG, Broder KR, Murray EL, Greenberg ME, Glover MJ, Likos AM, Posey DL, Klimov A, Lindstrom SE, Balish A, Medina MJ, Wallis TR, Guarner J, Paddock CD, Shieh WJ, Zaki SR, Sejvar JJ, Shay DK, Harper SA, Cox NJ, Fukuda K, Uyeki TM. Influenza-associated deaths among children in the United States, 2003-2004. N Engl J Med 2005; 353, 2559-67.

2. Molinari NA, Ortega-Sanchez IR, Messonnier ML, Thompson WW, Wortley PM, Weintraub E, Bridges CB. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine 2007; 25, 5086-96.

3. Estimates of deaths associated with seasonal influenza - United States, 1976-2007. MMWR Morb Mortal Wkly Rep 2010; 59, 1057-62.

4. Girard MP, Cherian T, Pervikov Y, Kieny MP. A review of vaccine research and development: human acute respiratory infections. Vaccine 2005; 23, 5708-24.

5. Shah NS, Greenberg JA, McNulty MC, Gregg KS, Riddell J, Mangino JE, Weber DM, Hebert CL, Marzec NS, Barron MA, Chaparro-Rojas F, Restrepo A, Hemmige V, Prasidthrathsint K, Cobb S, Herwaldt L, Raabe V, Cannavino CR, Hines AG, Bares SH, Antiporta PB, Scardina T, Patel U, Reid G, Mohazabnia P, Kachhdiya S, Le BM, Park CJ, Ostrowsky B, Robicsek A, Smith BA, Schied J, Bhatti MM, Mayer S, Sikka M, Murphy-Aguilu I, Patwari P, Abeles SR, Torriani FJ, Abbas Z, Toya S, Doktor K, Chakrabarti A, Doblecki-Lewis S, Looney DJ, David MZ. Severe Influenza in 33 US Hospitals, 2013-2014: Complications and Risk Factors for Death in 507 Patients. Infect Control Hosp Epidemiol 2015; 36, 1251-60.

6. Zheng W, Tao YJ. Structure and assembly of the influenza A virus ribonucleoprotein complex. FEBS Lett 2013; 587, 1206-14.

7. Buehler J, Navi D, Lorusso A, Vincent A, Lager K, Miller CL. Influenza A virus PB1-F2 protein expression is regulated in a strain-specific manner by sequences located downstream of the PB1-F2 initiation codon. J Virol 2013; 87, 10687-99.

8. Zamarin D, Garcia-Sastre A, Xiao X, Wang R, Palese P. Influenza virus PB1-F2 protein induces cell death through mitochondrial ANT3 and VDAC1. PLoS Pathog 2005; 1, e4.

9. Bullough PA, Hughson FM, Skehel JJ, Wiley DC. Structure of influenza haemagglutinin at the pH of membrane fusion. Nature 1994; 371, 37-43.

10. Ekiert DC, Bhabha G, Elsliger MA, Friesen RH, Jongeneelen M, Throsby M, Goudsmit J, Wilson IA. Antibody recognition of a highly conserved influenza virus epitope. Science 2009; 324, 246-51.

11. Krystal M, Elliott RM, Benz EW, Jr., Young JF, Palese P. Evolution of influenza A and B viruses: conservation of structural features in the hemagglutinin genes. Proc Natl Acad Sci U S A 1982; 79, 4800-4.

12. Tong S, Zhu X, Li Y, Shi M, Zhang J, Bourgeois M, Yang H, Chen X, Recuenco S, Gomez J, Chen LM, Johnson A, Tao Y, Dreyfus C, Yu W, McBride R, Carney PJ, Gilbert AT, Chang J, Guo Z, Davis CT, Paulson JC, Stevens J, Rupprecht CE, Holmes EC, Wilson IA, Donis RO. New world bats harbor diverse influenza A viruses. PLoS Pathog 2013; 9, e1003657.

13. Jefferson T, Rivetti A, Di Pietrantonj C, Demicheli V, Ferroni E. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev 2012; 8, CD004879.

14. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2011; 12, 36-44.

15. Pfleiderer M, Trouvin JH, Brasseur D, Granstrom M, Shivji R, Mura M, Cavaleri M. Summary of knowledge gaps related to quality and efficacy of current influenza vaccines. Vaccine 2014; 32, 4586-91.

16. Andersohn F, Bornemann R, Damm O, Frank M, Mittendorf T, Theidel U. Vaccination of children with a live-attenuated, intranasal influenza vaccine - analysis and evaluation through a Health Technology Assessment. GMS Health Technol Assess 2014; 10, Doc03.

17. Skowronski DM, Chambers C, Sabaiduc S, De Serres G, Dickinson JA, Winter AL, Drews SJ, Fonseca K, Charest H, Gubbay JB, Petric M, Krajden M, Kwindt TL, Martineau C, Eshaghi A, Bastien N, Li Y. Interim estimates of 2014/15 vaccine effectiveness against influenza A(H3N2) from Canada’s Sentinel Physician Surveillance Network, January 2015. Euro Surveill 2015; 20.

18. 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. Airborne transmission of influenza A/ H5N1 virus between ferrets. Science 2012; 336, 1534- 41.

19. Linster M, van Boheemen S, de Graaf M, Schrauwen EJ, Lexmond P, Manz B, Bestebroer TM, Baumann J, van Riel D, Rimmelzwaan GF, Osterhaus AD, Matrosovich M, Fouchier RA, Herfst S. Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus. Cell 2014; 157, 329-39.

20. 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. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 2012; 486, 420-8.

21. Terajima M, Babon JA, Co MD, Ennis FA. Crossreactive human B cell and T cell epitopes between influenza A and B viruses. Virol J 2013; 10, 244.

22. 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. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature 2008; 453, 667-71.

23. Skehel JJ, Bayley PM, Brown EB, Martin SR, Waterfield MD, White JM, Wilson IA, Wiley DC. Changes in the conformation of influenza virus hemagglutinin at the pH optimum of virus-mediated membrane fusion. Proc Natl Acad Sci U S A 1982; 79, 968-72.

24. Carragher DM, Kaminski DA, Moquin A, Hartson L, Randall TD. A novel role for non-neutralizing antibodies against nucleoprotein in facilitating resistance to influenza virus. J Immunol 2008; 181, 4168-76.

25. Vareckova E, Mucha V, Wharton SA, Kostolansky F. Inhibition of fusion activity of influenza A haemagglutinin mediated by HA2-specific monoclonal antibodies. Arch Virol 2003; 148, 469-86.

26. Terajima M, Co MD, Cruz J, Ennis FA. High AntibodyDependent Cellular Cytotoxicity Antibody Titers to H5N1 and H7N9 Avian Influenza A Viruses in Healthy US Adults and Older Children. J Infect Dis 2015; 212, 1052-60.

27. Jegaskanda S, Job ER, Kramski M, Laurie K, Isitman G, de Rose R, Winnall WR, Stratov I, Brooks AG, Reading PC, Kent SJ. Cross-reactive influenza-specific antibody-dependent cellular cytotoxicity antibodies in the absence of neutralizing antibodies. J Immunol 2013; 190, 1837-48.

28. Thomas PG, Keating R, Hulse-Post DJ, Doherty PC. Cell-mediated protection in influenza infection. Emerg Infect Dis 2006; 12, 48-54.

29. Kreijtz JH, de Mutsert G, van Baalen CA, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. Cross-recognition of avian H5N1 influenza virus by human cytotoxic T-lymphocyte populations directed to human influenza A virus. J Virol 2008; 82, 5161-6.

30. Kreijtz JH, Bodewes R, van Amerongen G, Kuiken T, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. Primary influenza A virus infection induces crossprotective immunity against a lethal infection with a heterosubtypic virus strain in mice. Vaccine 2007; 25, 612-20.

31. van de Sandt CE, Kreijtz JH, de Mutsert G, GeelhoedMieras MM, Hillaire ML, Vogelzang-van Trierum SE, Osterhaus AD, Fouchier RA, Rimmelzwaan GF. Human cytotoxic T lymphocytes directed to seasonal influenza A viruses cross-react with the newly emerging H7N9 virus. J Virol 2013; 88, 1684-93.

32. Hillaire ML, Vogelzang-van Trierum SE, Kreijtz JH, de Mutsert G, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. Human T-cells directed to seasonal influenza A virus cross-react with 2009 pandemic influenza A (H1N1) and swine-origin triple-reassortant H3N2 influenza viruses. J Gen Virol 2012; 94, 583-92.

33. Bodewes R, Kreijtz JH, Geelhoed-Mieras MM, van Amerongen G, Verburgh RJ, van Trierum SE, Kuiken T, Fouchier RA, Osterhaus AD, Rimmelzwaan GF. Vaccination against seasonal influenza A/H3N2 virus reduces the induction of heterosubtypic immunity against influenza A/H5N1 virus infection in ferrets. J Virol 2011; 85, 2695-702.

34. Florek NW, Weinfurter JT, Jegaskanda S, Brewoo JN, Powell TD, Young GR, Das SC, Hatta M, Broman KW, Hungnes O, Dudman SG, Kawaoka Y, Kent SJ, Stinchcomb DT, Osorio JE, Friedrich TC. Modified vaccinia virus Ankara encoding influenza virus hemagglutinin induces heterosubtypic immunity in macaques. J Virol 2014; 88, 13418-28.

35. Nakayama M, Shichinohe S, Itoh Y, Ishigaki H, Kitano M, Arikata M, Pham VL, Ishida H, Kitagawa N, Okamatsu M, Sakoda Y, Ichikawa T, Tsuchiya H, Nakamura S, Le QM, Ito M, Kawaoka Y, Kida H, Ogasawara K. Protection against H5N1 highly pathogenic avian and pandemic (H1N1) 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine. PLoS ONE 2014; 8, e82740.

36. Hillaire ML, van Trierum SE, Kreijtz JH, Bodewes R, Geelhoed-Mieras MM, Nieuwkoop NJ, Fouchier RA, Kuiken T, Osterhaus AD, Rimmelzwaan GF. Crossprotective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells. J Gen Virol 2011; 92, 2339-49.

37. Wilkinson TM, Li CK, Chui CS, Huang AK, Perkins M, Liebner JC, Lambkin-Williams R, Gilbert A, Oxford J, Nicholas B, Staples KJ, Dong T, Douek DC, McMichael AJ, Xu XN. Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med 2012; 18, 274-80.

38. McMichael AJ, Gotch FM, Noble GR, Beare PA. Cytotoxic T-cell immunity to influenza. N Engl J Med 1983; 309, 13-7.

39. Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W, Carman W, Bean T, Barclay W, Deeks JJ, Lalvani A. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med 2013; 19, 1305-12.

40. McKinstry KK, Strutt TM, Kuang Y, Brown DM, Sell S, Dutton RW, Swain SL. Memory CD4+ T cells protect against influenza through multiple synergizing mechanisms. J Clin Invest 2012; 122, 2847-56.

41. Boonnak K, Subbarao K. Memory CD4+ T cells: beyond «helper» functions. J Clin Invest 2012; 122, 2768-70.

42. Altenburg AF, Rimmelzwaan GF, de Vries RD. Virusspecific T cells as correlate of (cross-)protective immunity against influenza. Vaccine 2014; 33, 500-6.

43. LaMere MW, Lam HT, Moquin A, Haynes L, Lund FE, Randall TD, Kaminski DA. Contributions of antinucleoprotein IgG to heterosubtypic immunity against influenza virus. J Immunol 2011; 186, 4331-9.

44. Hillaire ML, Osterhaus AD, Rimmelzwaan GF. Induction of virus-specific cytotoxic T lymphocytes as a basis for the development of broadly protective influenza vaccines. J Biomed Biotechnol 2011; 2011, 939860.

45. Gianfrani C, Oseroff C, Sidney J, Chesnut RW, Sette A. Human memory CTL response specific for influenza A virus is broad and multispecific. Hum Immunol 2000; 61, 438-52.

46. Taylor DN, Treanor JJ, Sheldon EA, Johnson C, Umlauf S, Song L, Kavita U, Liu G, Tussey L, Ozer K, Hofstaetter T, Shaw A. Development of VAX128, a recombinant hemagglutinin (HA) influenza-flagellin fusion vaccine with improved safety and immune response. Vaccine 2012; 30, 5761-9.

47. Steel J, Lowen AC, Pena L, Angel M, Solorzano A, Albrecht R, Perez DR, Garcia-Sastre A, Palese P. Live attenuated influenza viruses containing NS1 truncations as vaccine candidates against H5N1 highly pathogenic avian influenza. J Virol 2009; 83, 1742-53.

48. Terajima M, Cruz J, Co MD, Lee JH, Kaur K, Wrammert J, Wilson PC, Ennis FA. Complement-dependent lysis of influenza a virus-infected cells by broadly crossreactive human monoclonal antibodies. J Virol 2011; 85, 13463-7.

49. Jegaskanda S, Weinfurter JT, Friedrich TC, Kent SJ. Antibody-dependent cellular cytotoxicity is associated with control of pandemic H1N1 influenza virus infection of macaques. J Virol 2013; 87, 5512-22.

50. Moody MA, Zhang R, Walter EB, Woods CW, Ginsburg GS, McClain MT, Denny TN, Chen X, Munshaw S, Marshall DJ, Whitesides JF, Drinker MS, Amos JD, Gurley TC, Eudailey JA, Foulger A, DeRosa KR, Parks R, Meyerhoff RR, Yu JS, Kozink DM, Barefoot BE, Ramsburg EA, Khurana S, Golding H, Vandergrift NA, Alam SM, Tomaras GD, Kepler TB, Kelsoe G, Liao HX, Haynes BF. H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination. PLoS ONE 2011; 6, e25797.

51. Margine I, Hai R, Albrecht RA, Obermoser G, Harrod AC, Banchereau J, Palucka K, Garcia-Sastre A, Palese P, Treanor JJ, Krammer F. H3N2 influenza virus infection induces broadly reactive hemagglutinin stalk antibodies in humans and mice. J Virol 2013; 87, 4728-37.

52. Corti D, Suguitan AL, Jr., Pinna D, Silacci C, Fernandez-Rodriguez BM, Vanzetta F, Santos C, Luke CJ, Torres-Velez FJ, Temperton NJ, Weiss RA, Sallusto F, Subbarao K, Lanzavecchia A. Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine. J Clin Invest 2010; 120, 1663-73.

53. Krammer F, Pica N, Hai R, Tan GS, Palese P. Hemagglutinin Stalk-Reactive Antibodies Are Boosted following Sequential Infection with Seasonal and Pandemic H1N1 Influenza Virus in Mice. J Virol 2012; 86, 10302-7.

54. Pica N, Hai R, Krammer F, Wang TT, Maamary J, Eggink D, Tan GS, Krause JC, Moran T, Stein CR, Banach D, Wrammert J, Belshe RB, Garcia-Sastre A, Palese P. Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses. Proc Natl Acad Sci U S A 2012; 109, 2573-8.

55. He XS, Sasaki S, Baer J, Khurana S, Golding H, Treanor JJ, Topham DJ, Sangster MY, Jin H, Dekker CL, Subbarao K, Greenberg HB. Heterovariant cross-reactive B-cell responses induced by the 2009 pandemic influenza virus A subtype H1N1 vaccine. J Infect Dis 2012; 207, 288-96.

56. Tamura M, Webster RG, Ennis FA. Antibodies to HA and NA augment uptake of influenza A viruses into cells via Fc receptor entry. Virology 1991; 182, 211-9.

57. Gauger PC, Vincent AL, Loving CL, Henningson JN, Lager KM, Janke BH, Kehrli ME, Jr., Roth JA. Kinetics of lung lesion development and pro-inflammatory cytokine response in pigs with vaccine-associated enhanced respiratory disease induced by challenge with pandemic (2009) A/H1N1 influenza virus. Vet Pathol 2012; 49, 900-12.

58. Gauger PC, Vincent AL, Loving CL, Lager KM, Janke BH, Kehrli ME, Jr., Roth JA. Enhanced pneumonia and disease in pigs vaccinated with an inactivated humanlike (delta-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus. Vaccine 2011; 29, 2712-9.

59. Kitikoon P, Nilubol D, Erickson BJ, Janke BH, Hoover TC, Sornsen SA, Thacker EL. The immune response and maternal antibody interference to a heterologous H1N1 swine influenza virus infection following vaccination. Vet Immunol Immunopathol 2006; 112, 117-28.

60. Vincent AL, Lager KM, Janke BH, Gramer MR, Richt JA. Failure of protection and enhanced pneumonia with a US H1N2 swine influenza virus in pigs vaccinated with an inactivated classical swine H1N1 vaccine. Vet Microbiol 2008; 126, 310-23.

61. Khurana S, Loving CL, Manischewitz J, King LR, Gauger PC, Henningson J, Vincent AL, Golding H. Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease. Sci Transl Med 2013; 5, 200ra114.

62. Vincent AL, Ma W, Lager KM, Richt JA, Janke BH, Sandbulte MR, Gauger PC, Loving CL, Webby RJ, Garcia-Sastre A. Live attenuated influenza vaccine provides superior protection from heterologous infection in pigs with maternal antibodies without inducing vaccine-associated enhanced respiratory disease. J Virol 2012; 86, 10597-605.

63. Gauger PC, Loving CL, Khurana S, Lorusso A, Perez DR, Kehrli ME, Jr., Roth JA, Golding H, Vincent AL. Live attenuated influenza A virus vaccine protects against A(H1N1)pdm09 heterologous challenge without vaccine associated enhanced respiratory disease. Virology 2014; 471-473, 93-104.

64. WHO Product Development for Vaccines Advisory Committee (PD-VAC) meeting – 2015. Available:

65. Heiny AT, Miotto O, Srinivasan KN, Khan AM, Zhang GL, Brusic V, Tan TW, August JT. Evolutionarily conserved protein sequences of influenza a viruses, avian and human, as vaccine targets. PLoS ONE 2007; 2, e1190.

66. Virelizier JL, Allison AC, Oxford JS, Schild GC. Early presence of ribonucleoprotein antigen on surface of influenza virus-infected cells. Nature 1977; 266, 52-4.

67. Fiers W, De Filette M, El Bakkouri K, Schepens B, Roose K, Schotsaert M, Birkett A, Saelens X. M2ebased universal influenza A vaccine. Vaccine 2009; 27, 6280-3.

68. Stepanova LA, Kotlyarov RY, Kovaleva AA, Potapchuk MV, Korotkov AV, Sergeeva MV, Kasianenko MA, Kuprianov VV, Ravin NV, Tsybalova LM, Skryabin KG, Kiselev OI. Protection against multiple influenza A virus strains induced by candidate recombinant vaccine based on heterologous M2e peptides linked to flagellin. PLoS ONE 2015; 10, e0119520.

69. Neirynck S, Deroo T, Saelens X, Vanlandschoot P, Jou WM, Fiers W. A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nat Med 1999; 5, 1157-63.

70. De Filette M, Ramne A, Birkett A, Lycke N, Lowenadler B, Min Jou W, Saelens X, Fiers W. The universal influenza vaccine M2e-HBc administered intranasally in combination with the adjuvant CTA1- DD provides complete protection. Vaccine 2006; 24, 544-51.

71. Stanekova Z, Kiraly J, Stropkovska A, Mikuskova T, Mucha V, Kostolansky F, Vareckova E. Heterosubtypic protective immunity against influenza A virus induced by fusion peptide of the hemagglutinin in comparison to ectodomain of M2 protein. Acta Virol 2011; 55, 61-7.

72. Krammer F, Palese P, Steel J. Advances in universal influenza virus vaccine design and antibody mediated therapies based on conserved regions of the hemagglutinin. Curr Top Microbiol Immunol 2014; 386, 301-21.

73. Krammer F, Hai R, Yondola M, Tan GS, Leyva-Grado VH, Ryder AB, Miller MS, Rose JK, Palese P, GarciaSastre A, Albrecht RA. Assessment of influenza virus hemagglutinin stalk-based immunity in ferrets. J Virol 2014; 88, 3432-42.

74. Krammer F, Palese P. Universal influenza virus vaccines: need for clinical trials. Nat Immunol 2013; 15, 3-5.

75. Krammer F, Palese P. Influenza virus hemagglutinin stalk-based antibodies and vaccines. Curr Opin Virol 2013; 3, 521-30.

76. 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, 6542-50.

77. Impagliazzo A, Milder F, Kuipers H, Wagner MV, Zhu X, Hoffman RM, van Meersbergen R, Huizingh J, Wanningen P, Verspuij J, de Man M, Ding Z, Apetri A, Kukrer B, Sneekes-Vriese E, Tomkiewicz D, Laursen NS, Lee PS, Zakrzewska A, Dekking L, Tolboom J, Tettero L, van Meerten S, Yu W, Koudstaal W, Goudsmit J, Ward AB, Meijberg W, Wilson IA, Radosevic K. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science 2015; 349, 1301-6.

78. Kanekiyo M, Wei CJ, Yassine HM, McTamney PM, Boyington JC, Whittle JR, Rao SS, Kong WP, Wang L, Nabel GJ. Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature 2013; 499, 102-6.

79. Yassine HM, Boyington JC, McTamney PM, Wei CJ, Kanekiyo M, Kong WP, Gallagher JR, Wang L, Zhang Y, Joyce MG, Lingwood D, Moin SM, Andersen H, Okuno Y, Rao SS, Harris AK, Kwong PD, Mascola JR, Nabel GJ, Graham BS. Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat Med 2015; 21, 1065-70.

80. Coughlan L, Mullarkey C, Gilbert S. Adenoviral vectors as novel vaccines for influenza. J Pharm Pharmacol 2015; 67, 382-99.

81. Dudek T, Knipe DM. Replication-defective viruses as vaccines and vaccine vectors. Virology 2006; 344, 230-9.

82. He F, Madhan S, Kwang J. Baculovirus vector as a delivery vehicle for influenza vaccines. Expert Rev Vaccines 2009; 8, 455-67.

83. Draper SJ, Cottingham MG, Gilbert SC. Utilizing poxviral vectored vaccines for antibody inductionprogress and prospects. Vaccine 2013; 31, 4223-30.

84. Price GE, Soboleski MR, Lo CY, Misplon JA, Pappas C, Houser KV, Tumpey TM, Epstein SL. Vaccination focusing immunity on conserved antigens protects mice and ferrets against virulent H1N1 and H5N1 influenza A viruses. Vaccine 2009; 27, 6512-21.

85. Chun S, Li C, Van Domselaar G, Wang J, Farnsworth A, Cui X, Rode H, Cyr TD, He R, Li X. Universal antibodies and their applications to the quantitative determination of virtually all subtypes of the influenza A viral hemagglutinins. Vaccine 2008; 26, 6068-76.

86. Sedova ES, Shcherbinin DN, Migunov AI, Smirnov Iu A, Logunov D, Shmarov MM, Tsybalova LM, Naroditskii BS, Kiselev OI, Gintsburg AL. Recombinant influenza vaccines. Acta Naturae 2013; 4, 17-27.

87. Dreyfus C, Laursen NS, Kwaks T, Zuijdgeest D, Khayat R, Ekiert DC, Lee JH, Metlagel Z, Bujny MV, Jongeneelen M, van der Vlugt R, Lamrani M, Korse HJ, Geelen E, Sahin O, Sieuwerts M, Brakenhoff JP, Vogels R, Li OT, Poon LL, Peiris M, Koudstaal W, Ward AB, Wilson IA, Goudsmit J, Friesen RH. Highly conserved protective epitopes on influenza B viruses. Science 2012; 337, 1343-8.

88. Kosor Krnic E, Gagro A, Drazenovic V, Kuzman I, Jeren T, Cecuk-Jelicic E, Kerhin-Brkljacic V, GjeneroMargan I, Kaic B, Rakusic S, Sabioncello A, Markotic A, Rabatic S, Mlinaric-Galinovic G, Dekaris D. Enumeration of haemagglutinin-specific CD8+ T cells after influenza vaccination using MHC class I peptide tetramers. Scand J Immunol 2008; 67, 86-94.

89. Status of Vaccine Research and Development of Universal Influenza Vaccine Prepared for WHO PD-VAC. Available:

90. Tabynov K, Sansyzbay A, Kydyrbayev Z, Yespembetov B, Ryskeldinova S, Zinina N, Assanzhanova N, Sultankulova K, Sandybayev N, Khairullin B, Kuznetsova I, Ferko B, Egorov A. Influenza viral vectors expressing the Brucella OMP16 or L7/L12 proteins as vaccines against B. abortus infection. Virol J 2014; 11, 69.

91. Sereinig S, Stukova M, Zabolotnyh N, Ferko B, Kittel C, Romanova J, Vinogradova T, Katinger H, Kiselev O, Egorov A. Influenza virus NS vectors expressing the mycobacterium tuberculosis ESAT-6 protein induce CD4+ Th1 immune response and protect animals against tuberculosis challenge. Clin Vaccine Immunol 2006; 13, 898-904.

92. Stukova MA, Sereinig S, Zabolotnyh NV, Ferko B, Kittel C, Romanova J, Vinogradova TI, Katinger H, Kiselev OI, Egorov A. Vaccine potential of influenza vectors expressing Mycobacterium tuberculosis ESAT- 6 protein. Tuberculosis (Edinb) 2006; 86, 236-46.

93. Kittel C, Ferko B, Kurz M, Voglauer R, Sereinig S, Romanova J, Stiegler G, Katinger H, Egorov A. Generation of an influenza A virus vector expressing biologically active human interleukin-2 from the NS gene segment. J Virol 2005; 79, 10672-7.

94. Kittel C, Sereinig S, Ferko B, Stasakova J, Romanova J, Wolkerstorfer A, Katinger H, Egorov A. Rescue of influenza virus expressing GFP from the NS1 reading frame. Virology 2004; 324, 67-73.

95. Ferko B, Stasakova J, Sereinig S, Romanova J, Katinger D, Niebler B, Katinger H, Egorov A. Hyperattenuated recombinant influenza A virus nonstructural-proteinencoding vectors induce human immunodeficiency virus type 1 Nef-specific systemic and mucosal immune responses in mice. J Virol 2001; 75, 8899- 908.

96. Ferko B, Katinger D, Grassauer A, Egorov A, Romanova J, Niebler B, Katinger H, Muster T. Chimeric influenza virus replicating predominantly in the murine upper respiratory tract induces local immune responses against human immunodeficiency virus type 1 in the genital tract. J Infect Dis 1998; 178, 1359-68.

97. Wacheck V, Egorov A, Groiss F, Pfeiffer A, Fuereder T, Hoeflmayer D, Kundi M, Popow-Kraupp T, Redlberger-Fritz M, Mueller CA, Cinatl J, Michaelis M, Geiler J, Bergmann M, Romanova J, Roethl E, Morokutti A, Wolschek M, Ferko B, Seipelt J, DickGudenus R, Muster T. A novel type of influenza vaccine: safety and immunogenicity of replicationdeficient influenza virus created by deletion of the interferon antagonist NS1. J Infect Dis 2009; 201, 354-62.


For citations:

Egorov A.Y. The challenges of creating a universal influenza vaccine. Microbiology Independent Research Journal (MIR Journal). 2016;3(1):1-12. (In Russ.)

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