Advances in Therapy

, Volume 28, Issue 2, pp 91–109 | Cite as

Prevention of serious respiratory syncytial virus-related illness. I: Disease pathogenesis and early attempts at prevention

  • Jessie R. Groothuis
  • J. Michael Hoopes
  • Val G. Hemming Jessie
Open Access


Respiratory syncytial virus (RSV) was first described 160 years ago but was not officially recognized as a cause of serious illness in children until the late 1950s. It has been estimated that virtually all children have had at least one RSV infection by their second birthday. RSV is responsible for annual disease outbreaks, usually during a defined winter seasonal period that can vary by community and year. RSV is recognized as the leading cause of hospitalization among young children worldwide. Infants of young chronologic age and children with predisposing factors, such as premature birth, pulmonary disease, or congenital heart disease, are most susceptible to serious illness. Unlike other viruses, immunity to RSV infection is incomplete and short lived, and reinfection is common throughout life. Initial attempts to develop a vaccine in the 1960s met with unexpected and tragic results; many children vaccinated with a formalin-inactivated wild-type virus developed serious pulmonary disease upon subsequent natural infection. Numerous other vaccine technologies have since been studied, including vectored approaches, virus-like particles, DNA vaccines, and live attenuated virus vaccine. As of early 2010, only two companies or institutions had RSV vaccine candidates in early clinical trials, and no vaccine is likely to be licensed for marketing in the immediate future.


children history immunoglobulin immunoprophylaxis monoclonal antibody respiratory syncytial virus vaccine 


  1. 1.
    Hall CB. Respiratory syncytial virus. In: Feigen RD, Cherry JD, eds. Textbook of Pediatric Infectious Diseases. Philadelphia, PA: WB Saunders; 1987:1653–1675.Google Scholar
  2. 2.
    Hall CB. Respiratory syncytial virus and parainfluenza virus. N Engl J Med. 2001;344:1917–1928.PubMedCrossRefGoogle Scholar
  3. 3.
    Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009;360:588–598.PubMedCrossRefGoogle Scholar
  4. 4.
    Leader S, Kohlhase K. Respiratory syncytial virus-coded pediatric hospitalizations, 1997 to 1999. Pediatr Infect Dis J. 2002;21:629–632.PubMedCrossRefGoogle Scholar
  5. 5.
    Ruuskanen O, Ogra PL. Respiratory syncytial virus. Curr Probl Pediatr. 1993;23:50–79.PubMedCrossRefGoogle Scholar
  6. 6.
    Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ. Bronchiolitis-associated hospitalizations among US children, 1980–1996. JAMA. 1999;282:1440–1446.PubMedCrossRefGoogle Scholar
  7. 7.
    Leader S, Kohlhase K. Recent trends in severe respiratory syncytial virus (RSV) among US infants, 1997 to 2000. J Pediatr. 2003;143:S127–132.PubMedGoogle Scholar
  8. 8.
    McLaurin K, Leader S. Growing impact of RSV hospitalizations among infants in the US, 1997–2002. Paper presented at: Pediatric Academic Societies’ Meeting; May 14–17, 2005; Washington, DC, USA.Google Scholar
  9. 9.
    Nair H, Nokes DJ, Gessner BD, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010;375:1545–1555.PubMedCrossRefGoogle Scholar
  10. 10.
    Carroll KN, Gebretsadik T, Griffin MR, et al. Increasing burden and risk factors for bronchiolitis-related medical visits in infants enrolled in a state health care insurance plan. Pediatrics. 2008;122:58–64.PubMedCrossRefGoogle Scholar
  11. 11.
    Forbes ML, Hall CB, Jackson A, Masaquel AS, Mahadevia PJ. Comparative costs of hospitalisation among infants at high risk for respiratory syncytial virus lower respiratory tract infection during the first year of life. J Med Econ. 2010;13:136–141.PubMedCrossRefGoogle Scholar
  12. 12.
    Ruotsalainen M, Piippo-Savolainen E, Hyvarinen MK, Korppi M. Respiratory morbidity in adulthood after respiratory syncytial virus hospitalization in infancy. Pediatr Infect Dis J. 2010;29:872–874.PubMedCrossRefGoogle Scholar
  13. 13.
    Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet. 1999;354:541–545.PubMedCrossRefGoogle Scholar
  14. 14.
    Sigurs N, Aljassim F, Kjellman B, et al. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Thorax. 2010;65:1045–1052.PubMedCrossRefGoogle Scholar
  15. 15.
    Eberle J. A Treatise on the Diseases and Physical Education of Children. Philadelphia, PA: Lippincott, Grambo and Co.; 1850.Google Scholar
  16. 16.
    Adams JM. Primary virus pneumonitis with cytoplasmic inclusion bodies: study of an epidemic involving thirty-two infants, with nine deaths. JAMA. 1941;116:925–933.Google Scholar
  17. 17.
    Adams JM, Green RG, Evans CA, Northrop B. Primary virus pneumonitis: a comparative study of two epidemics. J Pediatr. 1942;20:405–420.CrossRefGoogle Scholar
  18. 18.
    Blount RE Jr, Morris JA, Savage RE. Recovery of cytopathogenic agent from chimpanzees with coryza. Proc Soc Exp Biol Med. 1956;92:544–549.PubMedGoogle Scholar
  19. 19.
    Chanock R, Finberg L. Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). II. Epidemiologic aspects of infection in infants and young children. Am J Hyg. 1957;66:291–300.PubMedGoogle Scholar
  20. 20.
    Chanock R, Roizman B, Myers R. Recovery from infants with respiratory illness of a virus related to chimpanzee coryza agent (CCA). I. Isolation, properties and characterization. Am J Hyg. 1957;66:281–290.PubMedGoogle Scholar
  21. 21.
    Chin J, Magoffin RL, Shearer LA, Schieble JH, Lennette EH. Field evaluation of a respiratory syncytial virus vaccine and a trivalent parainfluenza virus vaccine in a pediatric population. Am J Epidemiol. 1969;89:449–463.PubMedGoogle Scholar
  22. 22.
    Fulginiti VA, Eller JJ, Sieber OF, Joyner JW, Minamitani M, Meiklejohn G. Respiratory virus immunization. I. A field trial of two inactivated respiratory virus vaccines; an aqueous trivalent parainfluenza virus vaccine and an alum-precipitated respiratory syncytial virus vaccine. Am J Epidemiol. 1969;89:435–448.PubMedGoogle Scholar
  23. 23.
    Kapikian AZ, Mitchell RH, Chanock RM, Shvedoff RA, Stewart CE. An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. Am J Epidemiol. 1969;89:405–421.PubMedGoogle Scholar
  24. 24.
    Kim HW, Canchola JG, Brandt CD, et al. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol. 1969;89:422–434.PubMedGoogle Scholar
  25. 25.
    Dreizin RS, Vyshnevetskaia LO, Bagdamian EE, Iankevich OD, Tarasova LB. Experimental RS virus infection of cotton rats. A viral and immunofluorescent study [in Russian]. Vopr Virusol. 1971;16:670–676.PubMedGoogle Scholar
  26. 26.
    Prince GA, Jenson AB, Horswood RL, Camargo E, Chanock RM. The pathogenesis of respiratory syncytial virus infection in cotton rats. Am J Pathol. 1978;93:771–791.PubMedGoogle Scholar
  27. 27.
    Prince GA, Horswood RL, Camargo E, Koenig D, Chanock RM. Mechanisms of immunity to respiratory syncytial virus in cotton rats. Infect Immun. 1983;42:81–87.PubMedGoogle Scholar
  28. 28.
    Belshe RB, Van Voris LP, Mufson MA. Parenteral administration of live respiratory syncytial virus vaccine: results of a field trial. J Infect Dis. 1982;145:311–319.PubMedCrossRefGoogle Scholar
  29. 29.
    Hemming VG, Rodriguez W, Kim HW, et al. Intravenous immunoglobulin treatment of respiratory syncytial virus infections in infants and young children. Antimicrob Agents Chemother. 1987;31:1882–1886.PubMedGoogle Scholar
  30. 30.
    Groothuis JR, Levin MJ, Rodriguez W, et al. Use of intravenous gamma globulin to passively immunize high-risk children against respiratory syncytial virus: safety and pharmacokinetics. The RSVIG Study Group. Antimicrob Agents Chemother. 1991;35:1469–1473.Google Scholar
  31. 31.
    Meissner HC, Fulton DR, Groothuis JR, et al. Controlled trial to evaluate protection of high-risk infants against respiratory syncytial virus disease by using standard intravenous immune globulin. Antimicrob Agents Chemother. 1993;37:1655–1658.PubMedGoogle Scholar
  32. 32.
    Belshe RB, Anderson EL, Walsh EE. Immunogenicity of purified F glycoprotein of respiratory syncytial virus: clinical and immune responses to subsequent natural infection in children. J Infect Dis. 1993;168:1024–1029.PubMedCrossRefGoogle Scholar
  33. 33.
    Tristram DA, Welliver RC, Mohar CK, Hogerman DA, Hildreth SW, Paradiso P. Immunogenicity and safety of respiratory syncytial virus subunit vaccine in seropositive children 18–36 months old. J Infect Dis. 1993;167:191–195.PubMedCrossRefGoogle Scholar
  34. 34.
    Falsey AR, Walsh EE. Safety and immunogenicity of a respiratory syncytial virus subunit vaccine (PFP-2) in ambulatory adults over age 60. Vaccine. 1996;14:1214–1218.PubMedCrossRefGoogle Scholar
  35. 35.
    Groothuis JR, King SJ, Hogerman DA, Paradiso PR, Simoes EA. Safety and immunogenicity of a purified F protein respiratory syncytial virus (PFP-2) vaccine in seropositive children with bronchopulmonary dysplasia. J Infect Dis. 1998;177:467–469.PubMedCrossRefGoogle Scholar
  36. 36.
    Piedra PA, Grace S, Jewell A, et al. Sequential annual administration of purified fusion protein vaccine against respiratory syncytial virus in children with cystic fibrosis. Pediatr Infect Dis J. 1998;17:217–224.PubMedCrossRefGoogle Scholar
  37. 37.
    Power UF, Nguyen TN, Rietveld E, et al. Safety and immunogenicity of a novel recombinant subunit respiratory syncytial virus vaccine (BBG2Na) in healthy young adults. J Infect Dis. 2001;184:1456–1460.PubMedCrossRefGoogle Scholar
  38. 38.
    Munoz FM, Piedra PA, Glezen WP. Safety and immunogenicity of respiratory syncytial virus purified fusion protein-2 vaccine in pregnant women. Vaccine. 2003;21:3465–3467.PubMedCrossRefGoogle Scholar
  39. 39.
    Groothuis JR, Simoes EA, Levin MJ, et al. Prophylactic administration of respiratory syncytial virus immune globulin to high-risk infants and young children. The Respiratory Syncytial Virus Immune Globulin Study Group. N Engl J Med. 1993;329:1524–1530.PubMedCrossRefGoogle Scholar
  40. 40.
    The PREVENT Study Group. Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis. Pediatrics. 1997;99:93–99.CrossRefGoogle Scholar
  41. 41.
    Simoes EA, Sondheimer HM, Top FH Jr, et al. Respiratory syncytial virus immune globulin for prophylaxis against respiratory syncytial virus disease in infants and children with congenital heart disease. The Cardiac Study Group. J Pediatr. 1998;133:492–499.Google Scholar
  42. 42.
    The IMpact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics. 1998;102:531–537.CrossRefGoogle Scholar
  43. 43.
    OraVax Reports Results from Phase III Trial of HNK20. Nosedrop for Respiratory Syncytial Virus in Infants [press release]. Cambridge (MA): OraVax; March 19, 1997.Google Scholar
  44. 44.
    Meissner HC, Groothuis JR, Rodriguez WJ, et al. Safety and pharmacokinetics of an intramuscular monoclonal antibody (SB 209763) against respiratory syncytial virus (RSV) in infants and young children at risk for severe RSV disease. Antimicrob Agents Chemother. 1999;43:1183–1188.PubMedGoogle Scholar
  45. 45.
    Rodriguez WJ, Gruber WC, Welliver RC, et al. Respiratory syncytial virus (RSV) immune globulin intravenous therapy for RSV lower respiratory tract infection in infants and young children at high risk for severe RSV infections: Respiratory Syncytial Virus Immune Globulin Study Group. Pediatrics. 1997;99:454–461.PubMedCrossRefGoogle Scholar
  46. 46.
    Feltes TF, Cabalka AK, Meissner HC, et al. Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease. J Pediatr. 2003;143:532–540.PubMedCrossRefGoogle Scholar
  47. 47.
    Carbonell-Estrany X, Simoes EA, Dagan R, et al. Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial. Pediatrics. 2010;125:e35–51.PubMedCrossRefGoogle Scholar
  48. 48.
    Feltes TF, Sondheimer HM, Harris BS, et al. A randomized controlled trial of RSV prophylaxis with motavizumab vs palivizumab in young children with hemodynamically significant congenital heart disease (CHD). Paper presented at: Pediatric Academic Societies Annual Meeting; May 1–4, 2010; Vancouver, BC, Canada.Google Scholar
  49. 49.
    Chandran A, Millar EV, Weatherholtz R, et al. Safety and efficacy of motavizumab in the prevention of RSV disease in healthy infants. Paper presented at: American Pediatric Society/77th Annual Meeting for the Society for Pediatric Research; May 4, 2008; Honolulu, HI, USA.Google Scholar
  50. 50.
    Beem M, Wright FH, Hamre D, Egerer R, Oehme M. Association of the chimpanzee coryza agent with acute respiratory disease in children. N Engl J Med. 1960;263:523–530.PubMedCrossRefGoogle Scholar
  51. 51.
    Chanock RM, Kim HW, Vargosko AJ, et al. Respiratory syncytial virus. I. Virus recovery and other observations during 1960 outbreak of bronchiolitis, pneumonia, and minor respiratory diseases in children. JAMA. 1961;176:647–653.PubMedGoogle Scholar
  52. 52.
    Parrott RH, Vargosko AJ, Kim HW, et al. Respiratory syncytial virus. II. Serologic studies over a 34-month period of children with bronchiolitis, pneumonia, and minor respiratory diseases. JAMA. 1961;176:653–657.PubMedGoogle Scholar
  53. 53.
    Adams JM, Imagawa DT, Zike K. Epidemic bronchiolitis and pneumonitis related to respiratory syncytial virus. JAMA. 1961;176:1037–1039.PubMedGoogle Scholar
  54. 54.
    Hamparian VV, Ketler A, Hilleman MR, et al. Studies of acute respiratory illnesses caused by respiratory syncytial virus. 1. Laboratory findings in 109 cases. Proc Soc Exp Biol Med. 1961;106:717–722.PubMedGoogle Scholar
  55. 55.
    Kapikian AZ, Bell JA, Mastrota FM, Johnson KM, Huebner RJ, Chanock RM. An outbreak of febrile illness and pneumonia associated with respiratory syncytial virus infection. Am J Hyg. 1961;74:234–248.PubMedGoogle Scholar
  56. 56.
    Peacock DB, Clarke SK. Respiratory syncytial virus in Britain. Lancet. 1961;ii:466.CrossRefGoogle Scholar
  57. 57.
    Rowe DS, Michaels RH. Isolation of the respiratory syncytial virus from a patient with pneumonia. Pediatrics. 1960;26:623–629.PubMedGoogle Scholar
  58. 58.
    Chanock RM, Parrott RH, Vargosko AJ, Kapikian AZ, Knight V, Johnson KM. Acute respiratory diseases of viral etiology. IV. Respiratory syncytial virus. Am J Public Health Nations Health. 1962;52:918–925.PubMedCrossRefGoogle Scholar
  59. 59.
    Beem M. Repeated infections with respiratory syncytial virus. J Immunol. 1967;98:1115–1122.PubMedGoogle Scholar
  60. 60.
    Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child. 1986;140:543–546.PubMedGoogle Scholar
  61. 61.
    Hall CB, Walsh EE, Long CE, Schnabel KC. Immunity to and frequency of reinfection with respiratory syncytial virus. J Infect Dis. 1991;163:693–698.PubMedCrossRefGoogle Scholar
  62. 62.
    Henderson FW, Collier AM, Clyde WA Jr, Denny FW. Respiratory-syncytial-virus infections, reinfections and immunity. A prospective, longitudinal study in young children. N Engl J Med. 1979;300:530–534.PubMedCrossRefGoogle Scholar
  63. 63.
    Bruhn FW, Yeager AS. Respiratory syncytial virus in early infancy. Circulating antibody and the severity of infection. Am J Dis Child. 1977;131:145–148.PubMedGoogle Scholar
  64. 64.
    Kasel JA, Walsh EE, Frank AL, Baxter BD, Taber LH, Glezen WP. Relation of serum antibody to glycoproteins of respiratory syncytial virus with immunity to infection in children. Viral Immunol. 1987;1:199–205.PubMedCrossRefGoogle Scholar
  65. 65.
    Lamprecht CL, Krause HE, Mufson MA. Role of maternal antibody in pneumonia and bronchiolitis due to respiratory syncytial virus. J Infect Dis. 1976;134:211–217.PubMedCrossRefGoogle Scholar
  66. 66.
    Ogilvie MM, Vathenen AS, Radford M, Codd J, Key S. Maternal antibody and respiratory syncytial virus infection in infancy. J Med Virol. 1981;7: 263–271.PubMedCrossRefGoogle Scholar
  67. 67.
    Parrott RH, Kim HW, Arrobio JO, et al. Epidemiology of respiratory syncytial virus infection in Washington, D.C. II. Infection and disease with respect to age, immunologic status, race and sex. Am J Epidemiol. 1973;98:289–300.PubMedGoogle Scholar
  68. 68.
    Welliver RC. Review of epidemiology and clinical risk factors for severe respiratory syncytial virus (RSV) infection. J Pediatr. 2003;143:S112–117.PubMedCrossRefGoogle Scholar
  69. 69.
    Committee on Infectious Diseases. Modified 69. recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. Pediatrics. 2009;124:1694–1701CrossRefGoogle Scholar
  70. 70.
    Makari D, Groothuis J. Health risks of the late-preterm infant. Neonatol Today. 2009;4:1–8.CrossRefGoogle Scholar
  71. 71.
    Engle WA, Tomashek KM, Wallman C. “Late-71. preterm” infants: a population at risk. Pediatrics. 2007;120:1390–1401.PubMedCrossRefGoogle Scholar
  72. 72.
    Boyce TG, Mellen BG, Mitchel EF Jr, Wright PF, Griffin MR. Rates of hospitalization for respiratory syncytial virus infection among children in Medicaid. J Pediatr. 2000;137:865–870.PubMedCrossRefGoogle Scholar
  73. 73.
    Colin AA, McEvoy C, Castile R. Respiratory morbidity and lung function in preterm infants of 32 to 36 weeks’ gestational age. Pediatrics. 2010;126:115–128.PubMedCrossRefGoogle Scholar
  74. 74.
    Law BJ, MacDonald N, Langley J, et al. Severe respiratory syncytial virus infection among otherwise healthy prematurely born infants: What are we trying to prevent? Paediatr Child Health. Vol 3;1998:402–404.PubMedGoogle Scholar
  75. 75.
    Willson DF, Landrigan CP, Horn SD, Smout RJ. Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia. J Pediatr. 2003;143:S142–149.PubMedCrossRefGoogle Scholar
  76. 76.
    Groothuis JR, Gutierrez KM, Lauer BA. Respiratory syncytial virus infection in children with bronchopulmonary dysplasia. Pediatrics. 1988;82:199–203.PubMedGoogle Scholar
  77. 77.
    MacDonald NE, Hall CB, Suffin SC, Alexson C, Harris PJ, Manning JA. Respiratory syncytial viral infection in infants with congenital heart disease. N Engl J Med. 1982;307:397–400.PubMedCrossRefGoogle Scholar
  78. 78.
    Navas L, Wang E, de Carvalho V, Robinson J. Improved outcome of respiratory syncytial virus infection in a high-risk hospitalized population of Canadian children. Pediatric Investigators Collaborative Network on Infections in Canada. J Pediatr. 1992;121:348–354.PubMedCrossRefGoogle Scholar
  79. 79.
    Panitch HB. Viral respiratory infections in children with technology dependence and neuromuscular disorders. Pediatr Infect Dis J. 2004;23:S222–227.PubMedCrossRefGoogle Scholar
  80. 80.
    Wilkesmann A, Ammann RA, Schildgen O, et al. Hospitalized children with respiratory syncytial virus infection and neuromuscular impairment face an increased risk of a complicated course. Pediatr Infect Dis J. 2007;26:485–491.PubMedCrossRefGoogle Scholar
  81. 81.
    Carbonell-Estrany X, Quero J. Hospitalization rates for respiratory syncytial virus infection in premature infants born during two consecutive seasons. Pediatr Infect Dis J. 2001;20:874–879.PubMedCrossRefGoogle Scholar
  82. 82.
    Figueras-Aloy J, Carbonell-Estrany X, Quero J. Case-control study of the risk factors linked to respiratory syncytial virus infection requiring hospitalization in premature infants born at a gestational age of 33–35 weeks in Spain. Pediatr Infect Dis J. 2004;23:815–820.PubMedCrossRefGoogle Scholar
  83. 83.
    Simoes EA. Environmental and demographic risk factors for respiratory syncytial virus lower respiratory tract disease. J Pediatr. 2003;143:S118–126.PubMedCrossRefGoogle Scholar
  84. 84.
    McConnochie KM, Roghmann KJ. Parental smoking, presence of older siblings, and family history of asthma increase risk of bronchiolitis. Am J Dis Child. 1986;140:806–812.PubMedGoogle Scholar
  85. 85.
    von Linstow ML, Hogh M, Nordbo SA, Eugen-Olsen J, Koch A, Hogh B. A community study of clinical traits and risk factors for human metapneumovirus and respiratory syncytial virus infection during the first year of life. Eur J Pediatr. 2008;167:1125–1133.CrossRefGoogle Scholar
  86. 86.
    Lanari M, Giovannini M, Giuffre L, et al. Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity. Pediatr Pulmonol. 2002;33:458–465.PubMedCrossRefGoogle Scholar
  87. 87.
    Resch B, Manzoni P, Lanari M. Severe respiratory syncytial virus (RSV) infection in infants with neuromuscular diseases and immune deficiency syndromes. Paediatr Respir Rev. 2009;10:148–153.PubMedCrossRefGoogle Scholar
  88. 88.
    Resch B, Pasnocht A, Gusenleitner W, Muller W. Rehospitalisations for respiratory disease and respiratory syncytial virus infection in preterm infants of 29–36 weeks gestational age. J Infect. 2005;50:397–403.PubMedCrossRefGoogle Scholar
  89. 89.
    Simoes EA, King SJ, Lehr MV, Groothuis JR. Preterm twins and triplets. A high-risk group for severe respiratory syncytial virus infection. Am J Dis Child. 1993;147:303–306.PubMedGoogle Scholar
  90. 90.
    Collins PL, Graham BS. Viral and host factors in human respiratory syncytial virus pathogenesis. J Virol. 2008;82:2040–2055.PubMedCrossRefGoogle Scholar
  91. 91.
    Yeung CY, Hobbs JR. Serum-gamma-G-globulin levels in normal premature, post-mature, and “small-for-dates” newborn babies. Lancet. 1968;i:1167–1170.CrossRefGoogle Scholar
  92. 92.
    Ballow M, Cates KL, Rowe JC, Goetz C, Desbonnet C. Development of the immune system in very low birth weight (less than 1500 g) premature infants: concentrations of plasma immunoglobulins and patterns of infections. Pediatr Res. 1986;20: 899–904.PubMedCrossRefGoogle Scholar
  93. 93.
    Brandenburg AH, Groen J, van Steensel-Moll HA, et al. Respiratory syncytial virus specific serum antibodies in infants under six months of age: limited serological response upon infection. J Med Virol. 1997;52:97–104.PubMedCrossRefGoogle Scholar
  94. 94.
    Hacimustafaoglu M, Celebi S, Aynaci E, et al. The progression of maternal RSV antibodies in the offspring. Arch Dis Child. 2004;89:52–53.PubMedCrossRefGoogle Scholar
  95. 95.
    Ochola R, Sande C, Fegan G, et al. The level and duration of RSV-specific maternal IgG in infants in Kilifi Kenya. PLoS ONE. 2009;4:e8088.PubMedCrossRefGoogle Scholar
  96. 96.
    Murphy BR, Alling DW, Snyder MH, et al. Effect of age and preexisting antibody on serum antibody response of infants and children to the F and G glycoproteins during respiratory syncytial virus infection. J Clin Microbiol. 1986;24:894–898.PubMedGoogle Scholar
  97. 97.
    Murphy BR, Prince GA, Walsh EE, et al. Dissociation between serum neutralizing and glycoprotein antibody responses of infants and children who received inactivated respiratory syncytial virus vaccine. J Clin Microbiol. 1986;24:197–202.PubMedGoogle Scholar
  98. 98.
    Murphy BR, Walsh EE. Formalin-inactivated respiratory syncytial virus vaccine induces antibodies to the fusion glycoprotein that are deficient in fusion-inhibiting activity. J Clin Microbiol. 1988;26:1595–1597.PubMedGoogle Scholar
  99. 99.
    Blanco JC, Boukhvalova MS, Shirey KA, Prince GA, Vogel SN. New insights for development of a safe and protective RSV vaccine. Hum Vaccin. 2010;6.Google Scholar
  100. 100.
    Castilow EM, Varga SM. Overcoming T cell-mediated immunopathology to achieve safe RSV vaccination. Future Virol. 2008;3:445–454.PubMedCrossRefGoogle Scholar
  101. 101.
    Delgado MF, Coviello S, Monsalvo AC, et al. Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease. Nat Med. 2009;15:34–41.PubMedCrossRefGoogle Scholar
  102. 102.
    Haynes LM, Jones LP, Barskey A, Anderson LJ, Tripp RA. Enhanced disease and pulmonary eosinophilia associated with formalin-inactivated respiratory syncytial virus vaccination are linked to G glycoprotein CX3C-CX3CR1 interaction and expression of substance P. J Virol. 2003;77:9831–9844.PubMedCrossRefGoogle Scholar
  103. 103.
    Johnson TR, Teng MN, Collins PL, Graham BS. Respiratory syncytial virus (RSV) G glycoprotein is not necessary for vaccine-enhanced disease induced by immunization with formalin-inactivated RSV. J Virol. 2004;78:6024–6032.PubMedCrossRefGoogle Scholar
  104. 104.
    Ponnuraj EM, Hayward AR, Raj A, Wilson H, Simoes EA. Increased replication of respiratory syncytial virus (RSV) in pulmonary infiltrates is associated with enhanced histopathological disease in bonnet monkeys (Macaca radiata) pre-immunized with a formalin-inactivated RSV vaccine. J Gen Virol. 2001;82:2663–2674.PubMedGoogle Scholar
  105. 105.
    Prince GA, Curtis SJ, Yim KC, Porter DD. Vaccine-enhanced respiratory syncytial virus disease in cotton rats following immunization with Lot 100 or a newly prepared reference vaccine. J Gen Virol. 2001;82:2881–2888.PubMedGoogle Scholar
  106. 106.
    Prince GA, Jenson AB, Hemming VG, et al. Enhancement of respiratory syncytial virus pulmonary pathology in cotton rats by prior intramuscular inoculation of formalin-inactivated virus. J Virol. 1986;57:721–728.PubMedGoogle Scholar
  107. 107.
    Sparer TE, Matthews S, Hussell T, et al. Eliminating a region of respiratory syncytial virus attachment protein allows induction of protective immunity without vaccine-enhanced lung eosinophilia. J Exp Med. 1998;187:1921–1926.PubMedCrossRefGoogle Scholar
  108. 108.
    Stevens WW, Sun J, Castillo JP, Braciale TJ. Pulmonary eosinophilia is attenuated by early responding CD8(+) memory T cells in a murine model of RSV vaccine-enhanced disease. Viral Immunol. 2009;22:243–251.PubMedCrossRefGoogle Scholar
  109. 109.
    Englund J. In search of a vaccine for respiratory syncytial virus: the saga continues. J Infect Dis. 2005;191:1036–1039.PubMedCrossRefGoogle Scholar
  110. 110.
    Dudas RA, Karron RA. Respiratory syncytial virus vaccines. Clin Microbiol Rev. 1998;11:430–439.PubMedGoogle Scholar
  111. 111.
    Durbin AP, Karron RA. Progress in the development of respiratory syncytial virus and parainfluenza virus vaccines. Clin Infect Dis. 2003;37:1668–1677.PubMedCrossRefGoogle Scholar
  112. 112.
    Kneyber MC, Kimpen JL. Advances in respiratory syncytial virus vaccine development. Curr Opin Investig Drugs. 2004;5:163–170.PubMedGoogle Scholar
  113. 113.
    van Drunen Littel-van den Hurk S, Mapletoft JW, Arsic N, Kovacs-Nolan J. Immunopathology of RSV infection: prospects for developing vaccines without this complication. Rev Med Virol. 2007;17:5–34.PubMedCrossRefGoogle Scholar
  114. 114.
    Schickli JH, Dubovsky F, Tang RS. Challenges in developing a pediatric RSV vaccine. Hum Vaccin. 2009;5:582–591.PubMedGoogle Scholar
  115. 115.
    Power UF. Respiratory syncytial virus (RSV) vaccines—two steps back for one leap forward. J Clin Virol. 2008;41:38–44.PubMedCrossRefGoogle Scholar
  116. 116.
    Clyde WA Jr. Experimental models for study of common respiratory viruses. Environ Health Perspect. 1980;35:107–112.PubMedCrossRefGoogle Scholar
  117. 117.
    Coates HV, Chanock RM. Experimental infection with respiratory syncytial virus in several species of animals. Am J Hyg. 1962;76:302–312.PubMedGoogle Scholar
  118. 118.
    Prince GA, Porter DD. The pathogenesis of respiratory syncytial virus infection in infant ferrets. Am J Pathol. 1976;82:339–352.PubMedGoogle Scholar
  119. 119.
    Prince GA, Horswood RL, Chanock RM. Quantitative aspects of passive immunity to respiratory syncytial virus infection in infant cotton rats. J Virol. 1985;55:517–520.PubMedGoogle Scholar
  120. 120.
    Siber GR, Leombruno D, Leszczynski J, et al. Comparison of antibody concentrations and protective activity of respiratory syncytial virus immune globulin and conventional immune globulin. J Infect Dis. 1994;169:1368–1373.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Healthcare 2011

Authors and Affiliations

  • Jessie R. Groothuis
    • 1
  • J. Michael Hoopes
    • 1
  • Val G. Hemming Jessie
    • 2
  1. 1.MedImmune, LLCGaithersburgUSA
  2. 2.Uniformed Services University of Health SciencesBethesdaUSA

Personalised recommendations