Prevention of serious respiratory syncytial virus-related illness. II: Immunoprophylaxis Authors First online: 04 February 2011 Received: 30 September 2010 DOI:
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Respiratory syncytial virus (RSV) causes significant morbidity in very young children, preterm infants with and without chronic lung disease, and children with hemodynamically significant congenital heart disease. In the absence of a safe and effective vaccine, alternative means of protecting high-risk infants and young children from serious RSV illness have been studied. Clinical observations and animal model data over the past 30 years suggested that RSV immunoglobulin G (IgG) neutralizing antibodies might offer protection from severe RSV lower respiratory tract disease. Transfer of adequate amounts of IgG to the fetus does not occur efficiently until the third trimester of pregnancy, which helps to explain why premature infants are at high risk of serious RSV illness. Efforts shifted toward the prophylactic monthly administration of standard immunoglobulins and, later, of RSV-enriched immunoglobulin in selected high-risk infants and young children. Although this approach proved effective, RSV-enriched immune globulin was not suitable for all patients and administration was labor intensive. The development of palivizumab, a monoclonal antibody that can bind to a specific antigenic site on the virus and prevent cell-to-cell spread of infection has since become the mainstay of RSV illness prevention in preterm infants and those with significant congenital heart disease. Palivizumab, the only monoclonal antibody approved for the prevention of RSV lower respiratory tract disease must be administered monthly throughout the RSV season and does not always prevent serious RSV illness. Further research to develop more effective and less labor-intensive immunoprophylactic agents is ongoing.
respiratory syncytial virus
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Hemming VG, Prince GA, Groothuis JR, Siber GR. Hyperimmune globulins in prevention and treatment of respiratory syncytial virus infections. Clin Microbiol Rev. 1995;8:22–33.
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.
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.
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.
Ottolini MG, Burnett MW. History of U.S. military contributions to the study of respiratory infections. Mil Med. 2005;170:66–70.
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.
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.
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.
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.
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.
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.
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.
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.
Prince GA, Hemming VG, Horswood RL, Chanock RM. Immunoprophylaxis and immunotherapy of respiratory syncytial virus infection in the cotton rat. Virus Res. 1985;3:193–206.
Hemming VG, Prince GA, Horswood RL, et al. Studies of passive immunotherapy for infections of respiratory syncytial virus in the respiratory tract of a primate model. J Infect Dis. 1985;152:1083–1087.
Siber GR, Leszcynski J, Pena-Cruz V, et al. Protective activity of a human respiratory syncytial virus immune globulin prepared from donors screened by microneutralization assay. J Infect Dis. 1992;165:456–463.
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.
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.
Ogra PL. Respiratory syncytial virus: the virus, the disease and the immune response. Paediatr Respir Rev. 2004;5(Suppl. A):S119–S126.
Ruuskanen O, Ogra PL. Respiratory syncytial virus. Curr Probl Pediatr. 1993;23:50–79.
Beeler JA, van Wyke Coelingh K. Neutralization epitopes of the F glycoprotein of respiratory syncytial virus: effect of mutation upon fusion function. J Virol. 1989;63:2941–2950.
Johnson S, Oliver C, Prince GA, et al. Development of a humanized monoclonal antibody (MEDI-493) with potent in vitro and in vivo activity against respiratory syncytial virus. J Infect Dis. 1997;176:1215–1224.
Tempest PR, Bremner P, Lambert M, et al. Reshaping a human monoclonal antibody to inhibit human respiratory syncytial virus infection in vivo. Biotechnology (NY). 1991;9:266–271.
Weltzin R, Traina-Dorge V, Soike K, et al. Intranasal monoclonal IgA antibody to respiratory syncytial virus protects rhesus monkeys against upper and lower respiratory tract infection. J Infect Dis. 1996;174:256–261.
OraVax Reports Results from Phase III Trial of HNK20 Nosedrop for Respiratory Syncytial Virus in Infants [press release]. Cambridge (MA): OraVax; March 19, 1997.
Davis CB, Hepburn TW, Urbanski JJ, et al. Preclinical pharmacokinetic evaluation of the respiratory syncytial virus-specific reshaped human monoclonal antibody RSHZ19. Drug Metab Dispos. 1995;23:1028–1036.
Everitt DE, Davis CB, Thompson K, et al. The pharmacokinetics, antigenicity, and fusioninhibition activity of RSHZ19, a humanized monoclonal antibody to respiratory syncytial virus, in healthy volunteers. J Infect Dis. 1996;174:463–469.
Fisher RG, Johnson JE, Dillon SB, Parker RA, Graham BS. Prophylaxis with respiratory syncytial virus F-specific humanized monoclonal antibody delays and moderately suppresses the native antibody response but does not impair immunity to late rechallenge. J Infect Dis. 1999;180:708–713.
Wyde PR, Moore DK, Hepburn T, et al. Evaluation of the protective efficacy of reshaped human monoclonal antibody RSHZ19 against respiratory syncytial virus in cotton rats. Pediatr Res. 1995;38:543–550.
Johnson S, Griego SD, Pfarr DS, et al. A direct comparison of the activities of two humanized respiratory syncytial virus monoclonal antibodies: MEDI-493 and RSHZl9. J Infect Dis. 1999;180:35–40.
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.
Huang K, Incognito L, Cheng X, Ulbrandt ND, Wu H. Respiratory syncytial virus-neutralizing monoclonal antibodies motavizumab and palivizumab inhibit fusion. J Virol. 2010;84:8132–8140.
DeVincenzo JP, Hall CB, Kimberlin DW, et al. Surveillance of clinical isolates of respiratory syncytial virus for palivizumab (Synagis)-resistant mutants. J Infect Dis. 2004;190:975–978.
Saez-Llorens X, Castano E, Null D, et al. Safety and pharmacokinetics of an intramuscular humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. The MEDI-493 Study Group. Pediatr Infect Dis J. 1998;17:787–791.
Wu SY, Bonaparte J, Pyati S. Palivizumab use in very premature infants in the neonatal intensive care unit. Pediatrics. 2004;114:e554–556.
Subramanian KN, Weisman LE, Rhodes T, et al. Safety, tolerance and pharmacokinetics of a humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. MEDI-493 Study Group. Pediatr Infect Dis J. 1998;17:110–115.
Malley R, DeVincenzo J, Ramilo O, et al. Reduction of respiratory syncytial virus (RSV) in tracheal aspirates in intubated infants by use of humanized monoclonal antibody to RSV F protein. J Infect Dis. 1998;178:1555–1561.
Cohen SA, Zanni R, Cohen A, Harrington M, Vanveldhuisen P, Boron ML. Palivizumab use in subjects with congenital heart disease: results from the 2000–2004 Palivizumab Outcomes Registry. Pediatr Cardiol. 2008;29:382–387.
Frogel M, Nerwen C, Cohen A, VanVeldhuisen P, Harrington M, Boron M. Prevention of hospitalization due to respiratory syncytial virus: results from the Palivizumab Outcomes Registry. J Perinatol. 2008;28:511–517.
Kim EY, Battaile JT, Patel AC, et al. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease. Nat Med. 2008;14:633–640.
Simoes EA, Groothuis JR, Carbonell-Estrany X, et al. Palivizumab prophylaxis, respiratory syncytial virus, and subsequent recurrent wheezing. J Pediatr. 2007;151:34–42.
Wu H, Pfarr DS, Johnson S, et al. Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract. J Mol Biol. 2007;368:652–665.
Wu H, Pfarr DS, Losonsky GA, Kiener PA. Immunoprophylaxis of RSV infection: advancing from RSV-IGIV to palivizumab and motavizumab. Curr Top Microbiol Immunol. 2008;317:103–123.
Wu H, Pfarr DS, Tang Y, et al. Ultra-potent antibodies against respiratory syncytial virus: effects of binding kinetics and binding valence on viral neutralization. J Mol Biol. 2005;350:126–144.
Bockova J, O’Brien KL, Oski J, et al. Respiratory syncytial virus infection in Navajo and White Mountain Apache children. Pediatrics. 2002;110:e20.
Junghans RP. Finally! The Brambell receptor (FcRB). Mediator of transmission of immunity and protection from catabolism for IgG. Immunol Res. 1997;16:29–57.
Dall’Acqua WF, Kiener PA, Wu H. Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J Biol Chem. 2006;281:23514–23524.
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