Avian influenza viruses: a severe threat of a pandemic in children?

  • John V. Williams
Part of the Birkhäuser Advances in Infectious Diseases book series (BAID)


Influenza virus is a leading cause of human respiratory illnesses, causing significant annual morbidity and mortality. The greatest severity of illness due to seasonal influenza occurs in infants less than 6 months of age and the elderly. In recent years, avian influenza virus infections with high mortality have occurred in humans. Many of these avian influenza virus infections have occurred in children, and unlike seasonal influenza, the most severe disease and highest death rates have occurred in children and young adults. Treatment and prevention options for avian influenza viruses are limited at present, although much research effort is directed toward these areas. Avian-derived influenza viruses are potential causes of pandemic influenza that could have a dramatic impact on children worldwide.


Influenza Virus Avian Influenza Influenza Vaccine Avian Influenza Virus H5N1 Influenza 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    World Health Organization (2006) Acute Respiratory Infections: Influenza. World Health Organization, GenevaGoogle Scholar
  2. 2.
    Neuzil KM, Mellen BG, Wright PF, Mitchel EF Jr, Griffin MR (2000) The effect of influenza on hospitalizations, outpatient visits, and courses of antibiotics in children. N Engl J Med 342: 225–231PubMedCrossRefGoogle Scholar
  3. 3.
    Neuzil KM, Zhu Y, Griffin MR, Edwards KM, Thompson JM, Tollefson SJ, Wright PF (2002) Burden of interpandemic influenza in children younger than 5 years: a 25-year prospective study. J Infect Dis 185: 147–152PubMedCrossRefGoogle Scholar
  4. 4.
    Glezen WP, Couch RB (1978) Interpandemic influenza in the Houston area, 1974–76. N Engl J Med 298: 587–592PubMedCrossRefGoogle Scholar
  5. 5.
    Glezen WP (1980) Considerations of the risk of influenza in children and indications for prophylaxis. Rev Infect Dis 2: 408–420PubMedGoogle Scholar
  6. 6.
    Claas EC, Kawaoka Y, de Jong JC, Masurel N, Webster RG (1994) Infection of children with avian-human reassortant influenza virus from pigs in Europe. Virology 204: 453–457PubMedCrossRefGoogle Scholar
  7. 7.
    Luk J, Gross P, Thompson WW (2001) Observations on mortality during the 1918 influenza pandemic. Clin Infect Dis 33: 1375–1378PubMedCrossRefGoogle Scholar
  8. 8.
    Johnson NP, Mueller J (2002) Updating the accounts: global mortality of the 1918–1920 “Spanish” influenza pandemic. Bull Hist Med 76: 105–115PubMedCrossRefGoogle Scholar
  9. 9.
    Taubenberger JK, Reid AH, Krafft AE, Bijwaard KE, Fanning TG (1997) Initial genetic characterization of the 1918 “Spanish” influenza virus. Science 275: 1793–1796PubMedCrossRefGoogle Scholar
  10. 10.
    Reid AH, Fanning TG, Hultin JV, Taubenberger JK (1999) Origin and evolution of the 1918 “Spanish” influenza virus hemagglutinin gene. Proc Natl Acad Sci USA 96: 1651–1656PubMedCrossRefGoogle Scholar
  11. 11.
    Reid AH, Fanning TG, Janczewski TA, Taubenberger JK (2000) Characterization of the 1918 “Spanish” influenza virus neuraminidase gene. Proc Natl Acad Sci USA 97: 6785–6790PubMedCrossRefGoogle Scholar
  12. 12.
    Basler CF, Reid AH, Dybing JK, Janczewski TA, Fanning TG, Zheng H, Salvatore M, Perdue ML, Swayne DE, Garcia-Sastre A et al (2001) Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes. Proc Natl Acad Sci USA 98: 2746–2751PubMedCrossRefGoogle Scholar
  13. 13.
    Reid AH, Fanning TG, Janczewski TA, McCall S, Taubenberger JK (2002) Characterization of the 1918 “Spanish” influenza virus matrix gene segment. J Virol 76: 10717–10723PubMedCrossRefGoogle Scholar
  14. 14.
    Reid AH, Fanning TG, Janczewski TA, Lourens RM, Taubenberger JK (2004) Novel origin of the 1918 pandemic influenza virus nucleoprotein gene. J Virol 78: 12462–12470PubMedCrossRefGoogle Scholar
  15. 15.
    Tumpey TM, Basler CF, Aguilar PV, Zeng H, Solorzano A, Swayne DE, Cox NJ, Katz JM, Taubenberger JK, Palese P, Garcia-Sastre A (2005) Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 310: 77–80PubMedCrossRefGoogle Scholar
  16. 16.
    Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG (2005) Characterization of the 1918 influenza virus polymerase genes. Nature 437: 889–893PubMedCrossRefGoogle Scholar
  17. 17.
    Tumpey TM, Garcia-Sastre A, Taubenberger JK, Palese P, Swayne DE, Pantin-Jackwood MJ, Schultz-Cherry S, Solorzano A, Van Rooijen N, Katz JM, Basler CF (2005) Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice. J Virol 79: 14933–14944PubMedCrossRefGoogle Scholar
  18. 18.
    Tumpey TM, Garcia-Sastre A, Taubenberger JK, Palese P, Swayne DE, Basler CF (2004) Pathogenicity and immunogenicity of influenza viruses with genes from the 1918 pandemic virus. Proc Natl Acad Sci USA 101: 3166–3171PubMedCrossRefGoogle Scholar
  19. 19.
    Kash JC, Basler CF, Garcia-Sastre A, Carter V, Billharz R, Swayne DE, Przygodzki RM, Taubenberger JK, Katze MG, Tumpey TM (2004) Global host immune response: pathogenesis and transcriptional profiling of type A influenza viruses expressing the hemagglutinin and neuraminidase genes from the 1918 pandemic virus. J Virol 78: 9499–9511PubMedCrossRefGoogle Scholar
  20. 20.
    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: 11533–11536PubMedCrossRefGoogle Scholar
  21. 21.
    Webster RG, Kawaoka Y, Bean WJ Jr (1986) Molecular changes in A/Chicken/Pennsylvania/83 (H5N2) influenza virus associated with acquisition of virulence. Virology 149: 165–173PubMedCrossRefGoogle Scholar
  22. 22.
    Horimoto T, Rivera E, Pearson J, Senne D, Krauss S, Kawaoka Y, Webster RG (1995) Origin and molecular changes associated with emergence of a highly pathogenic H5N2 influenza virus in Mexico. Virology 213: 223–230PubMedCrossRefGoogle Scholar
  23. 23.
    Cauthen AN, Swayne DE, Schultz-Cherry S, Perdue ML, Suarez DL (2000) Continued circulation in China of highly pathogenic avian influenza viruses encoding the hemagglutinin gene associated with the 1997 H5N1 outbreak in poultry and humans. J Virol 74: 6592–6599PubMedCrossRefGoogle Scholar
  24. 24.
    Ungchusak K, Auewarakul P, Dowell SF, Kitphati R, Auwanit W, Puthavathana P, Uiprasertkul M, Boonnak K, Pittayawonganon C, Cox NJ et al (2005) Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med 352: 333–340PubMedCrossRefGoogle Scholar
  25. 25.
    Olsen SJ, Ungchusak K, Sovann L, Uyeki TM, Dowell SF, Cox NJ, Aldis W, Chunsuttiwat S (2005) Family clustering of avian influenza A (H5N1). Emerg Infect Dis 11: 1799–1801PubMedGoogle Scholar
  26. 26.
    World Health Organization (2006) Avian influenza — situation in Indonesia — update 14. In: Disease Outbreak News, 23 May 2006Google Scholar
  27. 27.
    Hatta M, Gao P, Halfmann P, Kawaoka Y (2001) Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293: 1840–1842PubMedCrossRefGoogle Scholar
  28. 28.
    Rimmelzwaan GF, van Riel D, Baars M, Bestebroer TM, van Amerongen G, Fouchier RA, Osterhaus AD, Kuiken T (2006) Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts. Am J Pathol 168: 176–183; quiz 364PubMedCrossRefGoogle Scholar
  29. 29.
    Kuiken T, Rimmelzwaan G, van Riel D, van Amerongen G, Baars M, Fouchier R, Osterhaus A (2004) Avian H5N1 influenza in cats. Science 306: 241PubMedCrossRefGoogle Scholar
  30. 30.
    Zitzow LA, Rowe T, Morken T, Shieh WJ, Zaki S, Katz JM (2002) Pathogenesis of avian influenza A (H5N1) viruses in ferrets. J Virol 76: 4420–4429PubMedCrossRefGoogle Scholar
  31. 31.
    Govorkova EA, Rehg JE, Krauss S, Yen HL, Guan Y, Peiris M, Nguyen TD, Hanh TH, Puthavathana P, Long HT, Buranathai C, Lim W, Webster RG, Hoffmann E (2005) Lethality to ferrets of H5N1 influenza viruses isolated from humans and poultry in 2004. J Virol 79: 2191–2198PubMedCrossRefGoogle Scholar
  32. 32.
    Van Borm S, Thomas I, Hanquet G, Lambrecht B, Boschmans M, Dupont G, Decaestecker M, Snacken R, van den Berg T (2005) Highly pathogenic H5N1 influenza virus in smuggled Thai eagles, Belgium. Emerg Infect Dis 11: 702–705PubMedGoogle Scholar
  33. 33.
    World Organisation for Animal Health (2006) Update on avian influenza in animals (type H5). Available from: Scholar
  34. 34.
    World Health Organization (2005) Avian influenza — new areas with infection in birds — update 34. In: Disease Outbreak News, 13 Oct 2005Google Scholar
  35. 35.
    Chen H, Smith GJ, Li KS, Wang J, Fan XH, Rayner JM, Vijaykrishna D, Zhang JX, Zhang LJ, Guo CT et al (2006) Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control. Proc Natl Acad Sci USA 103: 2845–2850PubMedCrossRefGoogle Scholar
  36. 36.
    Subbarao K, Klimov A, Katz J, Regnery H, Lim W, Hall H, Perdue M, Swayne D, Bender C, Huang J et al (1998) Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science 279: 393–396PubMedCrossRefGoogle Scholar
  37. 37.
    Yuen KY, Chan PK, Peiris M, Tsang DN, Que TL, Shortridge KF, Cheung PT, To WK, Ho ET, Sung R, Cheng AF (1998) Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet 351: 467–471PubMedCrossRefGoogle Scholar
  38. 38.
    Peiris JS, Yu WC, Leung CW, Cheung CY, Ng WF, Nicholls JM, Ng TK, Chan KH, Lai ST, Lim WL et al (2004) Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet 363: 617–619PubMedCrossRefGoogle Scholar
  39. 39.
    Peiris M, Yuen KY, Leung CW, Chan KH, Ip PL, Lai RW, Orr WK, Shortridge KF (1999) Human infection with influenza H9N2. Lancet 354: 916–917PubMedCrossRefGoogle Scholar
  40. 40.
    Fouchier RA, Schneeberger PM, Rozendaal FW, Broekman JM, Kemink SA, Munster V, Kuiken T, Rimmelzwaan GF, Schutten M, Van Doornum et al (2004) Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci USA 101: 1356–1361PubMedCrossRefGoogle Scholar
  41. 41.
    Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, Chunsuthiwat S, Sawanpanyalert P, Kijphati R, Lochindarat S, Srisan P, Suwan P, Osotthanakorn Y et al (2005) Human disease from influenza A (H5N1), Thailand, 2004. Emerg Infect Dis 11: 201–209PubMedGoogle Scholar
  42. 42.
    Tran TH, Nguyen TL, Nguyen TD, Luong TS, Pham PM, Nguyen VC, Pham TS, Vo CD, Le TQ, Ngo TT et al (2004) Avian influenza A (H5N1) in 10 patients in Vietnam. N Engl J Med 350: 1179–1188PubMedCrossRefGoogle Scholar
  43. 43.
    Areechokchai D, Jiraphongsa C, Laosiritaworn Y, Hanshaoworakul W, O’Reilly M (2006) Investigation of avian influenza (H5N1) outbreak in humans-Thailand, 2004. Morb Mortal Wkly Rep 55(Suppl 1): 3–6Google Scholar
  44. 44.
    de Jong MD, Bach VC, Phan TQ, Vo MH, Tran TT, Nguyen BH, Beld M, Le TP, Truong HK, Nguyen VV et al (2005) Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. N Engl J Med 352: 686–691PubMedCrossRefGoogle Scholar
  45. 45.
    World Health Organization (2006) Epidemiology of WHO-confirmed human cases of avian influenza A (H5N1) infection. Wkly Epidemiol Rec 81: 249–257Google Scholar
  46. 46.
    Ng WF, To KF, Lam WW, Ng TK, Lee KC (2006) The comparative pathology of severe acute respiratory syndrome and avian influenza A subtype H5N1 — a review. Hum Pathol 37: 381–390PubMedCrossRefGoogle Scholar
  47. 47.
    To KF, Chan PK, Chan KF, Lee WK, Lam WY, Wong KF, Tang NL, Tsang DN, Sung RY, Buckley TA et al (2001) Pathology of fatal human infection associated with avian influenza A H5N1 virus. J Med Virol 63: 242–246PubMedCrossRefGoogle Scholar
  48. 48.
    Kuiken T, Rimmelzwaan GF, Van Amerongen G, Osterhaus AD (2003) Pathology of human influenza A (H5N1) virus infection in cynomolgus macaques (Macaca fascicularis). Vet Pathol 40: 304–310PubMedCrossRefGoogle Scholar
  49. 49.
    Uyeki TM (2003) Influenza diagnosis and treatment in children: a review of studies on clinically useful tests and antiviral treatment for influenza. Pediatr Infect Dis J 22: 164–177PubMedCrossRefGoogle Scholar
  50. 50.
    Centers for Disease Control and Prevention (2006) High levels of adamantane resistance among influenza A (H3N2) viruses and interim guidelines for use of antiviral agents — United States, 2005–06 influenza season. Morb Mortal Wkly Rep 55: 44–46Google Scholar
  51. 51.
    Cheung CL, Rayner JM, Smith GJ, Wang P, Naipospos TS, Zhang J, Yuen KY, Webster RG, Peiris JS, Guan Y, Chen H (2006) Distribution of amantadineresistant H5N1 avian influenza variants in Asia. J Infect Dis 193: 1626–1629PubMedCrossRefGoogle Scholar
  52. 52.
    Ilyushina NA, Govorkova EA, Webster RG (2005) Detection of amantadineresistant variants among avian influenza viruses isolated in North America and Asia. Virology 341: 102–106PubMedCrossRefGoogle Scholar
  53. 53.
    Le QM, Kiso M, Someya K, Sakai YT, Nguyen TH, Nguyen KH, Pham ND, Ngyen HH, Yamada S, Muramoto Y et al (2005) Avian flu: isolation of drugresistant H5N1 virus. Nature 437: 1108PubMedCrossRefGoogle Scholar
  54. 54.
    Hayden F, Klimov A, Tashiro M, Hay A, Monto A, McKimm-Breschkin J, Macken C, Hampson A, Webster RG, Amyard M, Zambon M (2005) Neuraminidase inhibitor susceptibility network position statement: antiviral resistance in influenza A/H5N1 viruses. Antivir Ther 10: 873–877PubMedGoogle Scholar
  55. 55.
    Taylor J, Weinberg R, Kawaoka Y, Webster RG, Paoletti E (1988) Protective immunity against avian influenza induced by a fowlpox virus recombinant. Vaccine 6: 504–508PubMedCrossRefGoogle Scholar
  56. 56.
    Swayne DE, Beck JR, Perdue ML, Beard CW (2001) Efficacy of vaccines in chickens against highly pathogenic Hong Kong H5N1 avian influenza. Avian Dis 45: 355–365PubMedCrossRefGoogle Scholar
  57. 57.
    Swayne DE, Perdue ML, Beck JR, Garcia M, Suarez DL (2000) Vaccines protect chickens against H5 highly pathogenic avian influenza in the face of genetic changes in field viruses over multiple years. Vet Microbiol 74: 165–172PubMedCrossRefGoogle Scholar
  58. 58.
    Karaca K, Swayne DE, Grosenbaugh D, Bublot M, Robles A, Spackman E, Nordgren R (2005) Immunogenicity of fowlpox virus expressing the avian influenza virus H5 gene (TROVAC AIV-H5) in cats. Clin Diagn Lab Immunol 12: 1340–1342PubMedCrossRefGoogle Scholar
  59. 59.
    De BK, Shaw MW, Rota PA, Harmon MW, Esposito JJ, Rott R, Cox NJ, Kendal AP (1988) Protection against virulent H5 avian influenza virus infection in chickens by an inactivated vaccine produced with recombinant vaccinia virus. Vaccine 6: 257–261PubMedCrossRefGoogle Scholar
  60. 60.
    Tumpey TM, Kapczynski DR, Swayne DE (2004) Comparative susceptibility of chickens and turkeys to avian influenza A H7N2 virus infection and protective efficacy of a commercial avian influenza H7N2 virus vaccine. Avian Dis 48: 167–176PubMedCrossRefGoogle Scholar
  61. 61.
    Halvorson DA (2002) The control of H5 or H7 mildly pathogenic avian influenza: a role for inactivated vaccine. Avian Pathol 31: 5–12PubMedCrossRefGoogle Scholar
  62. 62.
    Subbarao K, Chen H, Swayne D, Mingay L, Fodor E, Brownlee G, Xu X, Lu X, Katz J, Cox N, Matsuoka Y (2003) Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics. Virology 305: 192–200PubMedCrossRefGoogle Scholar
  63. 63.
    Liu M, Wood JM, Ellis T, Krauss S, Seiler P, Johnson C, Hoffmann E, Humberd J, Hulse D, Zhang Y et al (2003) Preparation of a standardized, efficacious agricultural H5N3 vaccine by reverse genetics. Virology 314: 580–590PubMedCrossRefGoogle Scholar
  64. 64.
    Horimoto T, Takada A, Iwatsuki-Horimoto K, Hatta M, Goto H, Kawaoka Y (2003) Generation of influenza A viruses with chimeric (type A/B) hemagglutinins. J Virol 77: 8031–8038PubMedCrossRefGoogle Scholar
  65. 65.
    Stech J, Garn H, Wegmann M, Wagner R, Klenk HD (2005) A new approach to an influenza live vaccine: modification of the cleavage site of hemagglutinin. Nat Med 11: 683–689PubMedCrossRefGoogle Scholar
  66. 66.
    Lu B, Zhou H, Ye D, Kemble G, Jin H (2005) Improvement of influenza A/Fujian/411/02 (H3N2) virus growth in embryonated chicken eggs by balancing the hemagglutinin and neuraminidase activities, using reverse genetics. J Virol 79: 6763–6771PubMedCrossRefGoogle Scholar
  67. 67.
    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: 8431–8439PubMedCrossRefGoogle Scholar
  68. 68.
    Palker T, Kiseleva I, Johnston K, Su Q, Toner T, Szymkowiak C, Kwan WS, Rubin B, Petrukhin L, Wlochowski J et al (2004) Protective efficacy of intranasal cold-adapted influenza A/New Caledonia/20/99 (H1N1) vaccines comprised of egg-or cell culture-derived reassortants. Virus Res 105: 183–194PubMedCrossRefGoogle Scholar
  69. 69.
    Subbarao K, Katz JM (2004) Influenza vaccines generated by reverse genetics. Curr Top Microbiol Immunol 283: 313–342PubMedGoogle Scholar
  70. 70.
    Ghendon YZ, Markushin SG, Akopova II, Koptiaeva IB, Nechaeva EA, Mazurkova LA, Radaeva IF, Kolokoltseva TD (2005) Development of cell culture (MDCK) live cold-adapted (CA) attenuated influenza vaccine. Vaccine 23: 4678–4684PubMedCrossRefGoogle Scholar
  71. 71.
    Oxford JS, Manuguerra C, Kistner O, Linde A, Kunze M, Lange W, Schweiger B, Spala G, Rebelo de Andrade H, Perez Brena PR et al (2005) A new European perspective of influenza pandemic planning with a particular focus on the role of mammalian cell culture vaccines. Vaccine 23: 5440–5449PubMedCrossRefGoogle Scholar
  72. 72.
    Subbarao K, Murphy BR, Fauci AS (2006) Development of effective vaccines against pandemic influenza. Immunity 24: 5–9PubMedCrossRefGoogle Scholar
  73. 73.
    Treanor JJ, Campbell JD, Zangwill KM, Rowe T, Wolff M (2006) Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine. N Engl J Med 354: 1343–1351PubMedCrossRefGoogle Scholar
  74. 74.
    Bresson JL, Perronne C, Launay O, Gerdil C, Saville M, Wood J, Hoschler K, Zambon MC (2006) Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial. Lancet 367: 1657–1664PubMedCrossRefGoogle Scholar
  75. 75.
    Garrison MW, Baker DE (1991) Therapeutic advances in the prevention of hepatitis B: yeast-derived recombinant hepatitis B vaccines. DICP 25: 617–627PubMedGoogle Scholar
  76. 76.
    Kuroda K, Hauser C, Rott R, Klenk HD, Doerfler W (1986) Expression of the influenza virus haemagglutinin in insect cells by a baculovirus vector. EMBO J 5: 1359–1365PubMedGoogle Scholar
  77. 77.
    Vanlandschoot P, Beirnaert E, Neirynck S, Saelens X, Jou WM, Fiers W (1996) Molecular and immunological characterization of soluble aggregated A/Victoria/3/75 (H3N2) influenza haemagglutinin expressed in insect cells. Arch Virol 141: 1715–1726PubMedCrossRefGoogle Scholar
  78. 78.
    Wang K, Holtz KM, Anderson K, Chubet R, Mahmoud W, Cox MM (2006) Expression and purification of an influenza hemagglutinin — one step closer to a recombinant protein-based influenza vaccine. Vaccine 24: 2176–2185PubMedCrossRefGoogle Scholar
  79. 79.
    Abe T, Takahashi H, Hamazaki H, Miyano-Kurosaki N, Matsuura Y, Takaku H (2003) Baculovirus induces an innate immune response and confers protection from lethal influenza virus infection in mice. J Immunol 171: 1133–1139PubMedGoogle Scholar
  80. 80.
    Brett IC, Johansson BE (2005) Immunization against influenza A virus: comparison of conventional inactivated, live-attenuated and recombinant baculovirus produced purified hemagglutinin and neuraminidase vaccines in a murine model system. Virology 339: 273–280PubMedCrossRefGoogle Scholar
  81. 81.
    Crawford J, Wilkinson B, Vosnesensky A, Smith G, Garcia M, Stone H, Perdue ML (1999) Baculovirus-derived hemagglutinin vaccines protect against lethal influenza infections by avian H5 and H7 subtypes. Vaccine 17: 2265–2274PubMedCrossRefGoogle Scholar
  82. 82.
    Olsen CW, McGregor MW, Dybdahl-Sissoko N, Schram BR, Nelson KM, Lunn DP, Macklin MD, Swain WF, Hinshaw VS (1997) Immunogenicity and efficacy of baculovirus-expressed and DNA-based equine influenza virus hemagglutinin vaccines in mice. Vaccine 15: 1149–1156PubMedCrossRefGoogle Scholar
  83. 83.
    Lakey DL, Treanor JJ, Betts RF, Smith GE, Thompson J, Sannella E, Reed G, Wilkinson BE, Wright PF (1996) Recombinant baculovirus influenza A hemagglutinin vaccines are well tolerated and immunogenic in healthy adults. J Infect Dis 174: 838–841PubMedGoogle Scholar
  84. 84.
    Powers DC, McElhaney JE, Florendo OA Jr, Manning MC, Upshaw CM, Bentley DW, Wilkinson BE (1997) Humoral and cellular immune responses following vaccination with purified recombinant hemagglutinin from influenza A (H3N2) virus. J Infect Dis 175: 342–351PubMedGoogle Scholar
  85. 85.
    Treanor JJ, Betts RF, Smith GE, Anderson EL, Hackett CS, Wilkinson BE, Belshe RB, Powers DC (1996) Evaluation of a recombinant hemagglutinin expressed in insect cells as an influenza vaccine in young and elderly adults. J Infect Dis 173: 1467–1470PubMedGoogle Scholar
  86. 86.
    Treanor JJ, Schiff GM, Couch RB, Cate TR, Brady RC, Hay CM, Wolff M, She D, Cox MM (2006) Dose-related safety and immunogenicity of a trivalent baculovirus-expressed influenza-virus hemagglutinin vaccine in elderly adults. J Infect Dis 193: 1223–1228PubMedCrossRefGoogle Scholar
  87. 87.
    Treanor JJ, Wilkinson BE, Masseoud F, Hu-Primmer J, Battaglia R, O’Brien D, Wolff M, Rabinovich G, Blackwelder W, Katz JM (2001) Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans. Vaccine 19: 1732–1737PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2007

Authors and Affiliations

  • John V. Williams
    • 1
  1. 1.Division of Pediatric Infectious DiseasesVanderbilt University Medical CenterNashvilleUSA

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