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Review

Pharmacological management of human respiratory syncytial virus infection

ORCID Icon, , ORCID Icon, , , & ORCID Icon show all
Pages 2293-2303 | Received 03 Jan 2020, Accepted 04 Aug 2020, Published online: 18 Aug 2020

References

  • Singanayagam A, Joshi P, Mallia P, et al. Viruses exacerbating chronic pulmonary disease: the role of immune modulation. BMC Med. 2012 Mar;10(1). DOI:10.1186/1741-7015-10-27.
  • Pickles RJ, DeVincenzo JP. Respiratory syncytial virus (RSV) and its propensity for causing bronchiolitis. J Pathol. 2015;235(2):266–276.
  • Calvo C, García-García ML, Blanco C, et al. Multiple simultaneous viral infections in infants with acute respiratory tract infections in Spain. J. Clin. Virol. 2008;42(3):268–272.
  • Obodai E, Odoom JK, Adiku T, et al. The significance of human respiratory syncytial virus (HRSV) in children from Ghana with acute lower respiratory tract infection: a molecular epidemiological analysis, 2006 and 2013-2014. PLoS One. 2018 Sep;13(9):e0203788.
  • Afonso CL, Amarasinghe GK, Bányai K, et al. Taxonomy of the order Mononegavirales: update 2016. Arch. Virol. 2016;161(8):2351–2360.
  • Bohmwald K, Gálvez NMS, Canedo-Marroquín G, et al. Contribution of cytokines to tissue damage during human respiratory syncytial virus infection. Front Immunol. 2019 Mar;10(MAR). DOI:10.3389/fimmu.2019.00452.
  • Collins PL, Fearns R, Graham BS. Respiratory syncytial virus: virology, reverse genetics, and pathogenesis of disease. Curr Top Microbiol Immunol. 2013. DOI:10.1007/978-3-642-38919-1-1
  • Liuzzi M, Mason SW, Cartier M, et al. Inhibitors of respiratory syncytial virus replication target cotranscriptional mRNA guanylylation by viral RNA-dependent RNA polymerase. J. Virol. 2005;79(20):13105–13115.
  • Bermingham A, Collins PL. The M2-2 protein of human respiratory syncytial virus is a regulatory factor involved in the balance between RNA replication and transcription. Proc Natl Acad Sci. 2002. DOI:10.1073/pnas.96.20.11259
  • Fearns R, Collins PL. Role of the M2-1 transcription antitermination protein of respiratory syncytial virus in sequential transcription.. J Virol. 1999;73(7):5852–5864.
  • Lindquist ME, Mainou BA, Dermody TS, et al. Activation of protein kinase R is required for induction of stress granules by respiratory syncytial virus but dispensable for viral replication. Virology. 2011 Apr;413(1):103–110.
  • Jeffree CE, Rixon HWML, Brown G, et al. Distribution of the attachment (G) glycoprotein and GM1 within the envelope of mature respiratory syncytial virus filaments revealed using field emission scanning electron microscopy. Virology. 2003;306(2):254–267.
  • Hacking D, Hull J. Respiratory syncytial virus - viral biology and the host response. J Infect. 2002 Jul;45(1):18–24.
  • Schmidt A, Couch R, Galasso G, et al. Current research on respiratory viral infections: third International Symposium. Antiviral Res. 2001;50(3):157–196.
  • Collins PL, Graham BS. Viral and host factors in human respiratory syncytial virus pathogenesis. J Virol. 2008;82(5):2040–2055.
  • Ruuskanen O, Ogra PL. Respiratory syncytial virus. Curr. Probl. Pediatr. 1993;23(2):50–79.
  • Mastrangelo P, Hegele RG. RSV fusion: time for a new model. Viruses. 2013;5(3):873–885.
  • Radu G, Caidi H, Miao C, et al. Prophylactic treatment with a G glycoprotein monoclonal antibody reduces pulmonary inflammation in Respiratory Syncytial Virus (RSV)-challenged naive and formalin-inactivated RSV-immunized BALB/c mice. J Virol. 2010 Sep;84(18):9632–9636.
  • Haynes LM, Caidi H, Radu GU, et al. Therapeutic monoclonal antibody treatment targeting respiratory syncytial virus (RSV) G protein mediates viral clearance and reduces the pathogenesis of RSV infection in BALB/c mice. J Infect Dis. 2009;200(3):439–447.
  • Harcourt J, Alvarez R, Jones LP, et al. Respiratory Syncytial Virus G protein and G protein CX3C motif adversely affect CX3CR1+ T cell responses. J. Immunol. 2006;176(3):1600–1608.
  • Johnson SM, McNally BA, Ioannidis I, et al. Respiratory Syncytial Virus uses CX3CR1 as a receptor on primary human airway epithelial cultures. PLoS Pathog. 2015;11(12):e1005318.
  • Bakre AA, Harcourt JL, Haynes LM, et al. The central conserved region (CCR) of respiratory syncytial virus (RSV) G protein modulates host miRNA expression and alters the cellular response to infection. Vaccines (Basel). 2017;5(3):16.
  • Karron RA, Buonagurio DA, Georgiu AF, et al. Respiratory syncytial virus (RSV) SH and G proteins are not essential for viral replication in vitro: clinical evaluation and molecular characterization of a cold-passaged, attenuated RSV subgroup B mutant. Proc. Natl. Acad. Sci. U. S. A. 1997;94(25):13961–13966.
  • Bawage SS, Tiwari PM, Pillai S, et al. Recent advances in diagnosis, prevention, and treatment of human respiratory syncytial virus. Adv Virol. 2013. DOI:10.1155/2013/595768.
  • Sun Z, Pan Y, Jiang S, et al. Respiratory syncytial virus entry inhibitors targeting the F protein. Viruses. 2013;5(1):211–225.
  • Tayyari F, Marchant D, Moraes TJ, et al. Identification of nucleolin as a cellular receptor for human respiratory syncytial virus. Nat. Med. 2011;17(9):1132–1135.
  • Triantafilou K, Kar S, Vakakis E, et al. Human respiratory syncytial virus viroporin SH: A viral recognition pathway used by the host to signal inflammasome activation. Thorax. 2013;68(1):66–75.
  • Gálvez NMS, Soto JA, Kalergis AM. New insights contributing to the development of effective vaccines and therapies to reduce the pathology caused by hRSV. Int J Mol Sci. 2017;18(8):1753.
  • Lo MS, Brazas RM, Holtzman MJ. Respiratory Syncytial Virus nonstructural proteins NS1 and NS2 mediate inhibition of stat2 expression and alpha/beta interferon responsiveness. J. Virol. 2005;79(14):9315–9319.
  • Shi T, Denouel A, Tietjen AK, et al. Global disease burden estimates of Respiratory Syncytial Virus–associated acute respiratory infection in older adults in 2015: A systematic review and meta-analysis. J Infect Dis. 2019 Mar. DOI:10.1093/infdis/jiz059.
  • Wennergren G, Kristjánsson S. Relationship between respiratory syncytial virus bronchiolitis and future obstructive airway diseases. Eur. Respir. J. 2001;18(6):1044–1058.
  • Falsey AR, Walsh EE. Respiratory syncytial virus infection in adults.. Clin Microbiol Rev. 2000;13(3):371–384.
  • Shi T, Balsells E, Wastnedge E, et al. Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: systematic review and meta–analysis. J Glob Health. 2015. DOI:10.7189/jogh.05.020416.
  • Sommer C. Risk factors for severe respiratory syncytial virus lower respiratory tract infection. Open Microbiol J. 2012. DOI:10.2174/1874285801105010144
  • Walsh EE, Falsey AR. Humoral and mucosal immunity in protection from natural respiratory syncytial virus infection in adults. J. Infect. Dis. 2004;190(2):373–378.
  • Lambert L, Sagfors AM, Openshaw PJM, et al. Immunity to RSV in early-life. Front Immunol. 2014 Sep;5. DOI:10.3389/fimmu.2014.00466.
  • Young S, O’Keeffe PT, Arnott J, et al. Lung function, airway responsiveness, and respiratory symptoms before and after bronchiolitis. Arch. Dis. Child. 1995;72(1):16–24.
  • Zomer-Kooijker K, Uiterwaal CSPM, Van Der Gugten AC, et al. Decreased lung function precedes severe respiratory syncytial virus infection and post-respiratory syncytial virus wheeze in term infants. Eur. Respir. J. 2014;44(3):666–674.
  • Gomez CR, Nomellini V, Faunce DE, et al. Innate immunity and aging. Exp Gerontol. 2008;43(8):718–728.
  • Cusi MG, Martorelli B, Di Genova G, et al. Age related changes in T cell mediated immune response and effector memory to Respiratory Syncytial Virus (RSV) in healthy subjects. Immun Ageing. 2010;7(1). DOI:10.1186/1742-4933-7-14
  • Falsey AR, Hennessey PA, Formica MA, et al. Respiratory Syncytial Virus infection in elderly and high-risk adults. N. Engl. J. Med. 2005;352(17):1749–1759.
  • Eisenhut M. Extrapulmonary manifestations of severe respiratory syncytial virus infection–a systematic review.. Crit Care. 2006. DOI:10.1186/cc4984
  • Kho N, Kerrigan JF, Tong T, et al. Respiratory syncytial virus infection and neurologic abnormalities: retrospective cohort study. J. Child Neurol. 2004;19(11):859–864.
  • Kawashima H, Ioi H, Ushio M, et al. Cerebrospinal fluid analysis in children with seizures from respiratory syncytial virus infection. Scand J Infect Dis. 2009 Jan;41(3):228–231.
  • Morichi S, Kawashima H, Ioi H, et al. Classification of acute encephalopathy in respiratory syncytial virus infection. J Infect Chemother. 2011 Jan;17(6):776–781.
  • Miyamoto K, Fujisawa M, Tsuboi T, et al. Systemic inflammatory response syndrome and prolonged hypoperfusion lesions in an infant with respiratory syncytial virus encephalopathy. J Infect Chemother. 2013 Jan;19(5):978–982.
  • Kawashima H, Kashiwagi Y, Ioi H, et al. Production of chemokines in respiratory syncytial virus infection with central nervous system manifestations. J. Infect. Chemother. 2012;18(6):827–831.
  • Bohmwald K, Gálvez NMS, Ríos M, et al. Neurologic alterations due to respiratory virus infections. Front Cell Neurosci. 2018;12. DOI:10.3389/fncel.2018.00386.
  • Morichi S, Morishita N, Ishida Y, et al. Examination of neurological prognostic markers in patients with respiratory syncytial virus-associated encephalopathy. Int. J. Neurosci. 2017;127(1):44–50.
  • Morichi S, Kawashima H, Ioi H, et al. Cerebrospinal fluid NOx (nitrite/nitrate) in RSV-infected children with CNS symptoms. J Infect. 2009 Oct;59(4):299–301.
  • Li X, Fu ZF, Alvarez R, et al. Respiratory syncytial virus (RSV) infects neuronal cells and processes that innervate the lung by a process involving RSV G protein.. J Virol. 2006;80(1):537–540.
  • 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(21):1524–1530.
  • Committee on Fetus and Newborn. Respiratory syncytial virus immune globulin intravenous: indications for Use. Pediatrics. 2004;99(4): 645–650.
  • Respiratory Syncytial Virus (RSV) PREVENT study group. Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis. The PREVENT study group.. Pediatrics. 1997;99(1):93–99.
  • 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(5):1215–1224.
  • Sáez-Llorens X, Castaño 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. Pediatr. Infect. Dis. J. 1998;17(9):787–791.
  • DeVincenzo JP, Malley R, Ramilo O, et al. Viral concentration in upper and lower respiratory secretions from respiratory syncytial virus (RSV) infected children treated with RSV monoclonal antibody (MEDI-493) † 830. Pediatr Res. 2007. DOI:10.1203/00006450-199804001-00851.
  • Village EG. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics. 1998;102(3):531–537.
  • Torchin H, Rousseau J, Marchand-Martin L, et al. Palivizumab administration in preterm infants in France: EPIPAGE-2 cohort study. Arch. Pediatr. 2018;25(2):89–94.
  • Subramanian KNS, 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. Pediatr Infect Dis J. 1998. DOI:10.1097/00006454-199802000-00006.
  • 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(3):652–665.
  • Wu H, Pfarr DS, Losonsky GA, et al. Immunoprophylaxis of RSV infection: advancing from RSV-IGIV to palivizumab and motavizumab. Curr Top Microbiol Immunol. 2008. DOI:10.1007/978-3-540-72146-8_4.
  • Mejías A, Chávez-Bueno S, Ríos AM, et al. Comparative effects of two neutralizing anti-respiratory syncytial virus (RSV) monoclonal antibodies in the RSV murine model: time versus Potency. Antimicrob. Agents Chemother.. 2005;49(11):4700–4707.
  • Fernández P, Trenholme A, Abarca K, et al. A phase 2, randomized, double-blind safety and pharmacokinetic assessment of respiratory syncytial virus (RSV) prophylaxis with motavizumab and palivizumab administered in the same season. BMC Pediatr.ics. 2010;10(1). DOI:10.1186/1471-2431-10-38
  • Carbonell-Estrany X, Simões EA, Dagan R, et al. Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial.. Pediatrics. 2010;125(1):e35–e51.
  • Boyoglu-Barnum S, Todd SO, Chirkova T, et al. An anti-G protein monoclonal antibody treats RSV disease more effectively than an anti-F monoclonal antibody in BALB/c mice. Virology. 2015;483:117–125.
  • Tripp RA, Power UF, Openshaw PJM, et al. Respiratory syncytial virus: targeting the g protein provides a new approach for an old problem. J. Virol.. 2017;92(3). DOI:10.1128/jvi.01302-17
  • Eiland LS. Respiratory syncytial virus: diagnosis, treatment and prevention.. J Pediatr Pharmacol Ther. 2009. DOI:10.5863/1551-6776-14.2.75
  • Cazzola M, Page CP, Calzetta L, et al. Pharmacology and therapeutics of bronchodilators. Pharmacol. Rev.. 2012;64(3):450–504.
  • A. & I. American Academy of Allergy, Bronchodilator definition. 2019. [cited 2020 Aug 10]. Available from: https://www.aaaai.org/conditions-and-treatments/conditions-dictionary/bronchodialator.
  • Celli BR, MacNee W, Agusti A, et al. Standards for the diagnosis and treatment of patients with COPD: A summary of the ATS/ERS position paper. Eur Respir J. 2004;23(6):932–946.
  • Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J. 2008;31(1):143–178.
  • Carande EJ, Pollard AJ, Drysdale SB. Management of respiratory syncytial virus bronchiolitis: 2015 survey of members of the European society for paediatric infectious diseases. Can. J. Infect. Dis. Med. Microbiol.. 2016;2016:1–5.
  • Karadag B, Ceran O, Guven G, et al. Efficacy of salbutamol and ipratropium bromide in the management of acute bronchiolitis – a clinical trial. Respiration. 2008;76(3):283–287.
  • Kellner JD, Ohlsson A, Gadomski AM, et al. Efficacy of bronchodilator therapy in bronchiolitis: A meta-analysis. Arch. Pediatr. Adolesc. Med.. 1996;150(11):1166.
  • Gadomski AM, Scribani MB. Bronchodilators for bronchiolitis. Cochrane Database Syst Rev. 2014. DOI:10.1002/14651858.CD001266.pub4
  • Spina D, Rigby PJ, Paterson JW, et al. Autoradiographic localization of beta-adrenoceptors in asthmatic human lung. Am. Rev. Respir. Dis.. 1989;140(5):1410–1415.
  • Steiner RWP. Treating acute bronchiolitis associated with RSV. Am Fam Physician. 2004 Jan 15;69(2):325-330.
  • Flores G, Horwitz RI. Efficacy of β2-agonists in bronchiolitis: A reappraisal and meta- analysis. Pediatrics. 1997;100(2):233–239.
  • Barr FE, Patel NR, Newth CJL. The pharmacologic mechanism by which inhaled epinephrine reduces airway obstruction in respiratory syncytial virus-associated bronchiolitis. J. Pediatr.. 2000;136(5):699–700.
  • Blumenthal MN, Brody TM. Studies on the mechanism of drug-induced bronchiolar relaxation in the guinea pig. J. Allergy. 1969;44(2):63–69.
  • Wainwright C, Altamirano L, Cheney M, et al. A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N. Engl. J. Med.. 2003;349(1):27–35.
  • Williams DM. Clinical pharmacology of corticosteroids. Respir Care. 2018;63(6):655–670.
  • Gupta P, Bhatia V. Corticosteroid physiology and principles of therapy. Indian J Pediatr. 2008;75(10):1039–1044.
  • Lee FEH, Walsh EE, Falsey AR. The effect of steroid use in hospitalized adults with respiratory syncytial virus-related illness. Chest. 2011;140(5):1155–1161.
  • Cade A, Eglin R, Graham M, et al. Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis. Arch. Dis. Child.. 2000;82(2):126–130.
  • Barnes PJ, Adcock IM. How do corticosteroids work in asthma? Ann Intern Med. 2003;139(5_Part_1):359.
  • Schwiebert LM, Stellato C, Schleimer RP. The epithelium as a target of glucocorticoid action in the treatment of asthma. Am J Respir Crit Care Med. 1996;154(2_pt_2):S16-S20.
  • Goebel J, Estrada B, Quinonez J, et al. Prednisolone plus albuterol versus albuterol alone in mild to moderate bronchiolitis. Clin. Pediatr. (Phila).. 2000;39(4):213–220.
  • Buckingham SC, Jafri HS, Bush AJ, et al. A randomized, double‐blind, placebo‐controlled trial of dexamethasone in severe respiratory syncytial virus (RSV) infection: effects on RSV quantity and clinical outcome. J. Infect. Dis.. 2002;185(9):1222–1228.
  • De Clercq E. Antiviral drugs: current state of the art. J. Clin. Virol.. 2001;22(1):73–89.
  • Jafri HS. Treatment of respiratory syncytial virus: antiviral therapies. Pediatr Infect Dis J. 2003;22(Supplement):S89-S93.
  • Lugo RA, Nahata MC. Pathogenesis and treatment of bronchiolitis. Clin Pharm. 1993. DOI:10.1093/ajhp/50.3.528
  • Lugo RA, Nahata MC. Pathogenesis and treatment of bronchiolitis. Am J Health Syst Pharm. 1993 Mar;50(3):528–548.
  • Guerguerian AM, Gauthier M, Lebel MH, et al. Ribavirin in ventilated respiratory syncytial virus bronchiolitis: A randomized, placebo-controlled trial. Am. J. Respir. Crit. Care Med.. 1999;160(3):829–834.
  • Edell D, Khoshoo V, Ross G, et al. Early ribavarin treatment of bronchiolitis: effect on long-term respiratory morbidity. Chest. 2002;122(3):935–939.
  • Zhang Y, Jamaluddin M, Wang S, et al. Ribavirin treatment up-regulates antiviral gene expression via the interferon-stimulated response element in respiratory syncytial virus-infected epithelial cells. J. Virol.. 2003;77(10):5933–5947.
  • Aljabr W, Touzelet O, Pollakis G, et al. Investigating the influence of ribavirin on human respiratory syncytial virus RNA synthesis by using a high-resolution transcriptome sequencing approach. J. Virol.. 2016;90(10):4876–4888.
  • Sidwell RW, Huffman JH, Khare GP, et al. Broad-spectrum antiviral activity of virazole: 1-β-D-ribofuranosyl-1, 2,4-triazole-3-carboxamide. Science. 1972;177(4050):705–706.
  • Turner TL, Kopp BT, Paul G, et al. Respiratory syncytial virus: current and emerging treatment options. Clin. Outcomes Res.. 2014;217. DOI:10.2147/ceor.s60710.
  • Chiou HE, Liu CL, Buttrey MJ, et al. Adverse effects of ribavirin and outcome in severe acute respiratory syndrome: experience in two medical centers. Chest. 2005;128(1):263–272.
  • Graham BS. Vaccines against respiratory syncytial virus: the time has finally come. Vaccine. 2016;34(30):3535–3541.
  • 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(4):422–434.
  • 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(8):1595–1597.
  • Russell RF, McDonald JU, Ivanova M, et al. Partial attenuation of respiratory syncytial virus with a deletion of a small hydrophobic gene is associated with elevated interleukin-1β responses.. J Virol. 2015;89(17):8974–8981.
  • Garg A, Spector SA. HIV Type 1 gp120-induced expansion of myeloid derived suppressor cells is dependent on interleukin 6 and suppresses immunity. J. Infect. Dis.. 2014;209(3):441–451.
  • Nguyen DT, Boes J, Van Amerongen G, et al. Infection-enhancing lipopeptides do not improve intranasal immunization of cotton rats with a delta-G candidate live-attenuated human respiratory syncytial virus vaccine. Hum Vaccines Immunother. 2013. DOI:10.4161/hv.26096.
  • Lambert SL, Aslam S, Stillman E, et al. A novel Respiratory Syncytial Virus (RSV) F subunit vaccine adjuvanted with GLA-SE elicits robust protective TH1-type humoral and cellular immunity in rodent models. PLoS One. 2015;10(3):e0119509.
  • Schneider-Ohrum K, Cayatte C, Bennett AS, et al. Immunization with low doses of recombinant postfusion or prefusion respiratory syncytial virus f primes for vaccine-enhanced disease in the cotton rat model independently of the presence of a Th1-biasing (GLA-SE) or Th2-biasing (alum) adjuvant. J Virol. 2017 Apr;91(8). DOI:10.1128/JVI.02180-16.
  • Fuentes S, Klenow L, Golding H, et al. Preclinical evaluation of bacterially produced RSV-G protein vaccine: strong protection against RSV challenge in cotton rat model. Sci. Rep.. 2017;7(1). DOI:10.1038/srep42428
  • Kurt-Jones EA, Popova L, Kwinn L, et al. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol. 2000;1(5):398–401.
  • Ghildyal R, Mills J, Murray M, et al. Respiratory syncytial virus matrix protein associates with nucleocapsids in infected cells. J Gen Virol. 2002;83(Pt 4):753–757.
  • Kim A-R, Lee D-H, Lee S-H, et al. Protection induced by virus-like particle vaccine containing tandem repeat gene of respiratory syncytial virus G protein.. PLoS One. 2018 Jan;13(1):e0191277.
  • Blanco JCG, Pletneva LM, McGinnes-Cullen L, et al. Efficacy of a respiratory syncytial virus vaccine candidate in a maternal immunization model. Nat Commun. 2018;9(1). DOI:10.1038/s41467-018-04216-6
  • Bueno SM, González PA, Cautivo KM, et al. Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG. Proc Natl Acad Sci. 2008;105(52):20822–20827.
  • Cautivo KM, Bueno SM, Cortes CM, et al. Efficient lung recruitment of respiratory syncytial virus-specific Th1 cells induced by recombinant bacillus calmette-guerin promotes virus clearance and protects from infection. J Immunol. 2010;185(12):7633–7645.
  • Céspedes PF, Rey-Jurado E, Espinoza JA, et al. A single, low dose of a cGMP recombinant BCG vaccine elicits protective T cell immunity against the human respiratory syncytial virus infection and prevents lung pathology in mice. Vaccine. 2017;35(5):757–766.
  • Soto JA, Gálvez NMS, Rivera CA, et al. Recombinant BCG vaccines reduce pneumovirus-caused airway pathology by inducing protective humoral immunity. Front Immunol. 2018 Dec;9. DOI:10.3389/fimmu.2018.02875.
  • PATH, RSV vaccine snapshot - PATH vaccine resource library. citedAug, 2019, 2015. http://www.path.org/vaccineresources/details.php?i=1562.
  • Beran J, Lickliter JD, Schwarz TF, et al. Safety and immunogenicity of 3 formulations of an investigational respiratory syncytial virus vaccine in nonpregnant women: results from 2 phase 2 trials. J Infect Dis. 1616;217. DOI:10.1093/infdis/jiy065.
  • ClinicalTrials.gov - A study to rank different dosages of antigen of glaxosmithkline (GSK) biologicals’ investigational respiratory syncytial virus (RSV) Vaccine (GSK3003891A), based on their immune response and safety, when administered to healthy adult .
  • ClinicalTrials.gov - Safety, Reactogenicity and Immunogenicity Study of Different Formulations of GlaxoSmithKline (GSK) Biologicals’ Investigational RSV Vaccine (GSK3003891A), in Healthy Women.
  • ClinicalTrials.gov - Safety and reactogenicity study of glaxosmithkline (GSK) biologicals’ investigational respiratory syncytial virus (RSV) vaccine (GSK3003891A) in healthy women.
  • Cunningham CK, Karron R, Muresan P, et al. Live-attenuated respiratory syncytial virus vaccine with deletion of RNA synthesis regulatory protein M2-2 and cold passage mutations is overattenuated. Open Forum Infect Dis. 2019 Jun;6(6). DOI:10.1093/ofid/ofz212.
  • ClinicalTrials.gov - Evaluating the infectivity, safety and immunogenicity of a recombinant live-attenuated respiratory syncytial virus vaccine (RSV LID cp ΔM2-2) in RSV-seronegative infants 6 to 24 months of age.
  • ClinicalTrials.gov - Infectivity, safety and immunogenicity of a recombinant live-attenuated respiratory syncytial virus vaccine (RSV LID cp ΔM2-2) in RSV-seronegative infants and children 6 to 24 months of age.
  • Crank MC, Ruckwardt TJ, Chen M, et al. A proof of concept for structure-based vaccine design targeting RSV in humans. Science. 2019;365(6452):505–509.
  • Malkin E, Yogev R, Abughali N, et al. Safety and immunogenicity of a live attenuated RSV vaccine in healthy RSV-seronegative children 5 to 24 months of age.. PLoS One. 2013;8(10):e77104.
  • Karron RA, Wright PF, Belshe RB, et al. Identification of a recombinant live attenuated respiratory syncytial virus vaccine candidate that is highly attenuated in infants. J Infect Dis. 2005;191(7):1093–1104.
  • ClinicalTrials.gov - Evaluating the Safety and Immune Response to a Single Dose of a Respiratory Syncytial Virus (RSV) Vaccine in RSV-Seronegative Infants and Children.
  • ClinicalTrials.gov - Evaluating the safety and immune response to a single dose of a respiratory syncytial virus (RSV) vaccine in infants and children
  • McLellan JS, Chen M, Leung S, et al. Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody.. Science. 2013 May;340(6136):1113–1117.
  • Sivapalasingam S, Caballero-Perez D, Houghton M, et al. Phase 1 study evaluating safety, tolerability, pharmacokinetics and immunogenicity of REGN2222 in healthy adults: a new human monoclonal RSV-F antibody for RSV prevention. Open Forum Infect Dis. 2015 Dec;2(suppl_1). DOI:10.1093/ofid/ofv133.628.
  • Domachowske JB, Khan AA, Esser MT, et al. Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion f-targeting monoclonal antibody administered as a single dose to healthy preterm infants. Pediatr. Infect. Dis. J.. 2018;37(9):886–892.
  • Regeneron Pharmaceuticals, Study to evaluate the efficacy and safety of REGN2222, for the prevention of medically attended rsv (respiratory syncytial virus) infection in preterm infants: NCT02325791 ClinicalTrials.gov, 2014. [cited 2020 Aug 10]. Available from: https://clinicaltrials.gov/ct2/show/NCT02325791?term=REGN2222&rank=1.
  • Mejias A, Garcia-Maurino C, Rodriguez-Fernandez R, et al. Development and clinical applications of novel antibodies for prevention and treatment of respiratory syncytial virus infection. Vaccine. 2017;35(3):496–502.
  • Cespedes PF, Bueno SM, Ramirez BA, et al. Surface expression of the hRSV nucleoprotein impairs immunological synapse formation with T cells. Proc Natl Acad Sci. 2014 Aug;111(31):E3214–E3223.
  • Gottlieb J, Zamora MR, Hodges T, et al. ALN-RSV01 for prevention of bronchiolitis obliterans syndrome after respiratory syncytial virus infection in lung transplant recipients. J Heart Lung Transplant. 2016;35(2):213–221.
  • DeVincenzo J, Lambkin-Williams R, Wilkinson T, et al. A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus. Proc Natl Acad Sci U S A. 2010;107(19):8800–8805.
  • ClinicalTrials.gov - Intranasal ALN-RSV01 administered to adult volunteers experimentally inoculated with respiratory syncytial virus
  • Porter D, Guo Y, Perry J, et al. 1646. combined resistance analyses from phase 2b studies of presatovir treatment in RSV-infected adults. Open Forum Infect Dis. 2018;5(suppl_1):S48–S49.
  • Hayden F, Whitley R. RSV antivirals: problems and progress. J Infect Dis. 2020. DOI:10.1093/infdis/jiaa029
  • ClinicalTrials.gov - Presatovir in lung transplant (LT) recipients with respiratory syncytial virus (RSV) infection
  • ClinicalTrials.gov - Presatovir in hematopoietic cell transplant recipients with respiratory syncytial virus infection of the upper respiratory tract
  • Perron M, Stray K, Kinkade A, et al. GS-5806 inhibits a broad range of respiratory syncytial virus clinical isolates by blocking the virus-cell fusion process. Antimicrob Agents Chemother. 2016;60(3):1264–1273.
  • De Vincenzo JP, McClure MW, Symons JA, et al. Activity of oral ALS-008176 in a respiratory syncytial virus challenge study. N. Engl. J. Med.. 2015;373(21):2048–2058.
  • DeVincenzo J, Tait D, Efthimiou J, et al. A randomized, placebo-controlled, respiratory syncytial virus human challenge study of the antiviral efficacy, safety, and pharmacokinetics of RV521, an inhibitor of the RSV-F protein. Antimicrob Agents Chemother. 2020 Jan;64(2):e01884–19.
  • Coakley E, Ahmad A, Larson K, et al. LB6. EDP-938, a Novel RSV N-inhibitor, administered once or twice daily was safe and demonstrated robust antiviral and clinical efficacy in a healthy volunteer challenge study. Open Forum Infect. Dis.. 2019;6(Supplement_2):S995-S995.
  • Stevens M, Rusch S, DeVincenzo J, et al. Antiviral activity of oral JNJ-53718678 in healthy adult volunteers challenged with respiratory syncytial virus: a placebo-controlled study. J Infect Dis. 2018;218(5):748–756.
  • PATH. RSV Vaccine and mAb Snapshot - PATH. PATH Vaccine Resour. Lib. 2019.

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