February 2011, Volume 28, Issue 2, pp 91-109,
Open Access This content is freely available online to anyone, anywhere at any time.
Date: 04 Feb 2011
Prevention of serious respiratory syncytial virus-related illness. I: Disease pathogenesis and early attempts at prevention
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.
This article is published with open access at Springerlink.com
Hall CB. Respiratory syncytial virus. In: Feigen RD, Cherry JD, eds. Textbook of Pediatric Infectious Diseases. Philadelphia, PA: WB Saunders; 1987:1653–1675.
Leader S, Kohlhase K. Recent trends in severe respiratory syncytial virus (RSV) among US infants, 1997 to 2000. J Pediatr. 2003;143:S127–132.PubMed
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.
Eberle J. A Treatise on the Diseases and Physical Education of Children. Philadelphia, PA: Lippincott, Grambo and Co.; 1850.
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.
Adams JM, Green RG, Evans CA, Northrop B. Primary virus pneumonitis: a comparative study of two epidemics. J Pediatr. 1942;20:405–420.CrossRef
Blount RE Jr, Morris JA, Savage RE. Recovery of cytopathogenic agent from chimpanzees with coryza. Proc Soc Exp Biol Med. 1956;92:544–549.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.PubMed
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.
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.PubMed
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.CrossRef
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.
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.CrossRef
OraVax Reports Results from Phase III Trial of HNK20. Nosedrop for Respiratory Syncytial Virus in Infants [press release]. Cambridge (MA): OraVax; March 19, 1997.
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.PubMed
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.PubMedCrossRef
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.
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.
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.PubMed
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.PubMed
Adams JM, Imagawa DT, Zike K. Epidemic bronchiolitis and pneumonitis related to respiratory syncytial virus. JAMA. 1961;176:1037–1039.PubMed
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.PubMed
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.PubMed
Peacock DB, Clarke SK. Respiratory syncytial virus in Britain. Lancet. 1961;ii:466.CrossRef
Rowe DS, Michaels RH. Isolation of the respiratory syncytial virus from a patient with pneumonia. Pediatrics. 1960;26:623–629.PubMed
Beem M. Repeated infections with respiratory syncytial virus. J Immunol. 1967;98:1115–1122.PubMed
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.PubMed
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.PubMed
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.PubMed
Committee on Infectious Diseases. Modified 69. recommendations for use of palivizumab for prevention of respiratory syncytial virus infections. Pediatrics. 2009;124:1694–1701CrossRef
Makari D, Groothuis J. Health risks of the late-preterm infant. Neonatol Today. 2009;4:1–8.CrossRef
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.PubMed
Groothuis JR, Gutierrez KM, Lauer BA. Respiratory syncytial virus infection in children with bronchopulmonary dysplasia. Pediatrics. 1988;82:199–203.PubMed
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.PubMed
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.CrossRef
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.PubMedCrossRef
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.PubMed
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.CrossRef
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.PubMed
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.PubMed
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.PubMed
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.
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.PubMedCrossRef
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.PubMed
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.PubMed
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.PubMed
Dudas RA, Karron RA. Respiratory syncytial virus vaccines. Clin Microbiol Rev. 1998;11:430–439.PubMed
Kneyber MC, Kimpen JL. Advances in respiratory syncytial virus vaccine development. Curr Opin Investig Drugs. 2004;5:163–170.PubMed
Schickli JH, Dubovsky F, Tang RS. Challenges in developing a pediatric RSV vaccine. Hum Vaccin. 2009;5:582–591.PubMed
Coates HV, Chanock RM. Experimental infection with respiratory syncytial virus in several species of animals. Am J Hyg. 1962;76:302–312.PubMed
Prince GA, Porter DD. The pathogenesis of respiratory syncytial virus infection in infant ferrets. Am J Pathol. 1976;82:339–352.PubMed
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.PubMed
- Prevention of serious respiratory syncytial virus-related illness. I: Disease pathogenesis and early attempts at prevention
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Advances in Therapy
Volume 28, Issue 2 , pp 91-109
- Cover Date
- Print ISSN
- Online ISSN
- Springer Healthcare Communications
- Additional Links
- monoclonal antibody
- respiratory syncytial virus
- Industry Sectors