Advanced Search
REVIEW ARTICLE
Korean J Pediatr 2012 September;55(9) :309-315.
Published online 2012 September 14.        doi:https://doi.org/10.3345/kjp.2012.55.9.309
Need for a safe vaccine against respiratory syncytial virus infection
Joo-Young Kim (Kim JY), Jun Chang (Chang C)
Division of Life & Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea
Corresponding Author: Jun Chang ,Tel: +82-2-3277-2549, Fax: +82-2-3277-3051, Email: tcell@ewha.ac.kr
Copyright © 2012 by The Korean Pediatric Society
ABSTRACT
Human respiratory syncytial virus (HRSV) is a major cause of severe respiratory tract illnesses in infants and young children worldwide. Despite its importance as a respiratory pathogen, there is currently no licensed vaccine for HRSV. Following failure of the initial trial of formalin-inactivated virus particle vaccine, continuous efforts have been made for the development of safe and efficacious vaccines against HRSV. However, several obstacles persist that delay the development of HRSV vaccine, such as the immature immune system of newborn infants and the possible Th2-biased immune responses leading to subsequent vaccine-enhanced diseases. Many HRSV vaccine strategies are currently being developed and evaluated, including live-attenuated viruses, subunit-based, and vector-based candidates. In this review, the current HRSV vaccines are overviewed and the safety issues regarding asthma and vaccine-induced pathology are discussed.
Keywords: Respiratory syncytial viruses | Vaccines | Asthma | Pathology
 
REFERENCE
1. Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, 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.
2. 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.
3. Welliver RC, Wong DT, Sun M, Middleton E Jr, Vaughan RS, Ogra PL. The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection. N Engl J Med 1981;305:841–846.
4. Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 2005;352:1749–1759.
5. Walsh EE, Hall CB, Briselli M, Brandriss MW, Schlesinger JJ. Immunization with glycoprotein subunits of respiratory syncytial virus to protect cotton rats against viral infection. J Infect Dis 1987;155:1198–1204.
6. Connors M, Collins PL, Firestone CY, Murphy BR. Respiratory syncytial virus (RSV) F, G, M2 (22K), and N proteins each induce resistance to RSV challenge, but resistance induced by M2 and N proteins is relatively short-lived. J Virol 1991;65:1634–1637.
7. Johnson PR, Spriggs MK, Olmsted RA, Collins PL. The G glycoprotein of human respiratory syncytial viruses of subgroups A and B: extensive sequence divergence between antigenically related proteins. Proc Natl Acad Sci U S A 1987;84:5625–5629.
8. Jang JE, Lee JB, Kim KH, Park SM, Shim BS, Cheon IS, et al. Evaluation of protective efficacy of respiratory syncytial virus vaccine against A and B subgroup human isolates in Korea. PLoS One 2011;6:e23797.
9. Piippo-Savolainen E, Remes S, Kannisto S, Korhonen K, Korppi M. Asthma and lung function 20 years after wheezing in infancy: results from a prospective follow-up study. Arch Pediatr Adolesc Med 2004;158:1070–1076.
10. Sigurs N, Aljassim F, Kjellman B, Robinson PD, Sigurbergsson F, Bjarnason R, et al. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Thorax 2010;65:1045–1052.
11. Wu P, Dupont WD, Griffin MR, Carroll KN, Mitchel EF, Gebretsadik T, et al. Evidence of a causal role of winter virus infection during infancy in early childhood asthma. Am J Respir Crit Care Med 2008;178:1123–1129.
12. Dakhama A, Park JW, Taube C, El Gazzar M, Kodama T, Miyahara N, et al. Alteration of airway neuropeptide expression and development of airway hyperresponsiveness following respiratory syncytial virus infection. Am J Physiol Lung Cell Mol Physiol 2005;288:L761–L770.
13. Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, Jensen K, et al. Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Am J Epidemiol 1969;89:422–434.
14. Singh AM, Moore PE, Gern JE, Lemanske RF Jr, Hartert TV. Bronchiolitis to asthma: a review and call for studies of gene-virus interactions in asthma causation. Am J Respir Crit Care Med 2007;175:108–119.
15. Copenhaver CC, Gern JE, Li Z, Shult PA, Rosenthal LA, Mikus LD, et al. Cytokine response patterns, exposure to viruses, and respiratory infections in the first year of life. Am J Respir Crit Care Med 2004;170:175–180.
16. Makela MJ, Tripp R, Dakhama A, Park JW, Ikemura T, Joetham A, et al. Prior airway exposure to allergen increases virus-induced airway hyperresponsiveness. J Allergy Clin Immunol 2003;112:861–869.
17. van der Sande MA, Kidd IM, Goetghebuer T, Martynoga RA, Magnusen A, Allen S, et al. Severe respiratory syncytial virus infection in early life is associated with increased type 2 cytokine production in Gambian children. Clin Exp Allergy 2002;32:1430–1435.
18. Culley FJ, Pollott J, Openshaw PJ. Age at first viral infection determines the pattern of T cell-mediated disease during reinfection in adulthood. J Exp Med 2002;196:1381–1386.
19. Han LL, Alexander JP, Anderson LJ. Respiratory syncytial virus pneumonia among the elderly: an assessment of disease burden. J Infect Dis 1999;179:25–30.
20. McIntosh K, McQuillin J, Gardner PS. Cell-free and cell-bound antibody in nasal secretions from infants with respiratory syncytial virus infection. Infect Immun 1979;23:276–281.
21. Aberle JH, Aberle SW, Dworzak MN, Mandl CW, Rebhandl W, Vollnhofer G, et al. Reduced interferon-gamma expression in peripheral blood mononuclear cells of infants with severe respiratory syncytial virus disease. Am J Respir Crit Care Med 1999;160:1263–1268.
22. Bui RH, Molinaro GA, Kettering JD, Heiner DC, Imagawa DT, St Geme JW Jr. Virus-specific IgE and IgG4 antibodies in serum of children infected with respiratory syncytial virus. J Pediatr 1987;110:87–90.
23. Rabatic S, Gagro A, Lokar-Kolbas R, Krsulovic-Hresic V, Vrtar Z, Popow-Kraupp T, et al. Increase in CD23+ B cells in infants with bronchiolitis is accompanied by appearance of IgE and IgG4 antibodies specific for respiratory syncytial virus. J Infect Dis 1997;175:32–37.
24. Russi JC, Delfraro A, Borthagaray MD, Velazquez B, García-Barreno B, Hortal M. Evaluation of immunoglobulin E-specific antibodies and viral antigens in nasopharyngeal secretions of children with respiratory syncytial virus infections. J Clin Microbiol 1993;31:819–823.
25. Dakhama A, Lee YM, Ohnishi H, Jing X, Balhorn A, Takeda K, et al. Virus-specific IgE enhances airway responsiveness on reinfection with respiratory syncytial virus in newborn mice. J Allergy Clin Immunol 2009;123:138–145.e5.
26. Dakhama A, Park JW, Taube C, Chayama K, Balhorn A, Joetham A, et al. The role of virus-specific immunoglobulin E in airway hyperresponsiveness. Am J Respir Crit Care Med 2004;170:952–959.
27. Rosenberg HF, Dyer KD, Domachowske JB. Eosinophils and their interactions with respiratory virus pathogens. Immunol Res 2009;43:128–137.
28. Rosenberg HF, Dyer KD, Domachowske JB. Respiratory viruses and eosinophils: exploring the connections. Antiviral Res 2009;83:1–9.
29. Phipps S, Lam CE, Mahalingam S, Newhouse M, Ramirez R, Rosenberg HF, et al. Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus. Blood 2007;110:1578–1586.
30. Johnson S, Oliver C, Prince GA, Hemming VG, Pfarr DS, Wang SC, 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.
31. Graham BS, Bunton LA, Wright PF, Karzon DT. Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice. J Clin Invest 1991;88:1026–1033.
32. Alwan WH, Record FM, Openshaw PJ. CD4+ T cells clear virus but augment disease in mice infected with respiratory syncytial virus. Comparison with the effects of CD8+ T cells. Clin Exp Immunol 1992;88:527–536.
33. 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.
34. 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.
35. Waris ME, Tsou C, Erdman DD, Zaki SR, Anderson LJ. Respiratory synctial virus infection in BALB/c mice previously immunized with formalin-inactivated virus induces enhanced pulmonary inflammatory response with a predominant Th2-like cytokine pattern. J Virol 1996;70:2852–2860.
36. De Swart RL, Kuiken T, Timmerman HH, van Amerongen G, Van Den Hoogen BG, Vos HW, et al. Immunization of macaques with formalin-inactivated respiratory syncytial virus (RSV) induces interleukin-13-associated hypersensitivity to subsequent RSV infection. J Virol 2002;76:11561–11569.
37. Connors M, Giese NA, Kulkarni AB, Firestone CY, Morse HC 3rd, Murphy BR. Enhanced pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of interleukin-4 (IL-4) and IL-10. J Virol 1994;68:5321–5325.
38. Taylor G, Stott EJ, Bew M, Fernie BF, Cote PJ, Collins AP, et al. Monoclonal antibodies protect against respiratory syncytial virus infection in mice. Immunology 1984;52:137–142.
39. Sparer TE, Matthews S, Hussell T, Rae AJ, Garcia-Barreno B, Melero JA, 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.
40. Martinez I, Melero JA. Enhanced neutralization of human respiratory syncytial virus by mixtures of monoclonal antibodies to the attachment (G) glycoprotein. J Gen Virol 1998;79(Pt 9):2215–2220.
41. Bastien N, Trudel M, Simard C. Complete protection of mice from respiratory syncytial virus infection following mucosal delivery of synthetic peptide vaccines. Vaccine 1999;17:832–836.
42. Johnson TR, Johnson JE, Roberts SR, Wertz GW, Parker RA, Graham BS. Priming with secreted glycoprotein G of respiratory syncytial virus (RSV) augments interleukin-5 production and tissue eosinophilia after RSV challenge. J Virol 1998;72:2871–2880.
43. Openshaw PJ, Clarke SL, Record FM. Pulmonary eosinophilic response to respiratory syncytial virus infection in mice sensitized to the major surface glycoprotein G. Int Immunol 1992;4:493–500.
44. Hancock GE, Speelman DJ, Heers K, Bortell E, Smith J, Cosco C. Generation of atypical pulmonary inflammatory responses in BALB/c mice after immunization with the native attachment (G) glycoprotein of respiratory syncytial virus. J Virol 1996;70:7783–7791.
45. Tebbey PW, Hagen M, Hancock GE. Atypical pulmonary eosinophilia is mediated by a specific amino acid sequence of the attachment (G) protein of respiratory syncytial virus. J Exp Med 1998;188:1967–1972.
46. Srikiatkhachorn A, Braciale TJ. Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine secretion and pulmonary eosinophilia during experimental murine respiratory syncytial virus infection. J Exp Med 1997;186:421–432.
47. Johnson TR, Varga SM, Braciale TJ, Graham BS. Vbeta14(+) T cells mediate the vaccine-enhanced disease induced by immunization with respiratory syncytial virus (RSV) G glycoprotein but not with formalinin-activated RSV. J Virol 2004;78:8753–8760.
48. 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.
49. Yu JR, Kim S, Lee JB, Chang J. Single intranasal immunization with recombinant adenovirus-based vaccine induces protective immunity against respiratory syncytial virus infection. J Virol 2008;82:2350–2357.
50. Crowe JE Jr, Firestone CY, Murphy BR. Passively acquired antibodies suppress humoral but not cell-mediated immunity in mice immunized with live attenuated respiratory syncytial virus vaccines. J Immunol 2001;167:3910–3918.
51. Pringle CR, Filipiuk AH, Robinson BS, Watt PJ, Higgins P, Tyrrell DA. Immunogenicity and pathogenicity of a triple temperature-sensitive modified respiratory syncytial virus in adult volunteers. Vaccine 1993;11:473–478.
52. Wright PF, Karron RA, Belshe RB, Thompson J, Crowe JE Jr, Boyce TG, et al. Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy. J Infect Dis 2000;182:1331–1342.
53. Karron RA, Wright PF, Belshe RB, Thumar B, Casey R, Newman F, et al. Identification of a recombinant live attenuated respiratory syncytial virus vaccine candidate that is highly attenuated in infants. J Infect Dis 2005;191:1093–1104.
54. Wright PF, Karron RA, Madhi SA, Treanor JJ, King JC, O'Shea A, et al. The interferon antagonist NS2 protein of respiratory syncytial virus is an important virulence determinant for humans. J Infect Dis 2006;193:573–581.
55. Murphy BR, Sotnikov AV, Lawrence LA, Banks SM, Prince GA. Enhanced pulmonary histopathology is observed in cotton rats immunized with formalin-inactivated respiratory syncytial virus (RSV) or purified F glycoprotein and challenged with RSV 3-6 months after immunization. Vaccine 1990;8:497–502.
56. Murphy BR, Sotnikov A, Paradiso PR, Hildreth SW, Jenson AB, Baggs RB, et al. Immunization of cotton rats with the fusion (F) and large (G) glycoproteins of respiratory syncytial virus (RSV) protects against RSV challenge without potentiating RSV disease. Vaccine 1989;7:533–540.
57. Prince GA, Denamur F, Deschamps M, Garcon N, Prieels JP, Slaoui M, et al. Monophosphoryl lipid A adjuvant reverses a principal histologic parameter of formalin-inactivated respiratory syncytial virus vaccine-induced disease. Vaccine 2001;19:2048–2054.
58. Hancock GE, Heers KM, Pryharski KS, Smith JD, Tiberio L. Adjuvants recognized by toll-like receptors inhibit the induction of polarized type 2 T cell responses by natural attachment (G) protein of respiratory syncytial virus. Vaccine 2003;21:4348–43
59. de Waal L, Power UF, Yuksel S, van Amerongen G, Nguyen TN, Niesters HG, et al. Evaluation of BBG2Na in infant macaques: specific immune responses after vaccination and RSV challenge. Vaccine 2004;22:915–922.
60. Power UF, Nguyen TN, Rietveld E, de Swart RL, Groen J, Osterhaus AD, et al. Safety and immunogenicity of a novel recombinant subunit respiratory syncytial virus vaccine (BBG2Na) in healthy young adults. J Infect Dis 2001;184:1456–14
61. Durbin AP, Karron RA. Progress in the development of respiratory syncytial virus and parainfluenza virus vaccines. Clin Infect Dis 2003;37:1668–1677.
62. Kohlmann R, Schwannecke S, Tippler B, Ternette N, Temchura VV, Tenbusch M, et al. Protective efficacy and immunogenicity of an adenoviral vector vaccine encoding the codon-optimized F protein of respiratory syncytial virus. J Virol 2009;83:12601–12610.
63. Hsu KH, Lubeck MD, Davis AR, Bhat RA, Selling BH, Bhat BM, et al. Immunogenicity of recombinant adenovirus-respiratory syncytial virus vaccines with adenovirus types 4, 5, and 7 vectors in dogs and a chimpanzee. J Infect Dis 1992;166:769–775.
64. Takimoto T, Hurwitz JL, Zhan X, Krishnamurthy S, Prouser C, Brown B, et al. Recombinant Sendai virus as a novel vaccine candidate for respiratory syncytial virus. Viral Immunol 2005;18:255–266.
65. Schmidt AC, McAuliffe JM, Murphy BR, Collins PL. Recombinant bovine/human parainfluenza virus type 3 (B/HPIV3) expressing the respiratory syncytial virus (RSV) G and F proteins can be used to achieve simultaneous mucosal immunization against RSV and HPIV3. J Virol 2001;75:4594–4603.
66. Elliott MB, Chen T, Terio NB, Chong SY, Abdullah R, Luckay A, et al. Alphavirus replicon particles encoding the fusion or attachment glycoproteins of respiratory syncytial virus elicit protective immune responses in BALB/c mice and functional serum antibodies in rhesus macaques. Vaccine 2007;25:7132–7144.
67. Mok H, Lee S, Utley TJ, Shepherd BE, Polosukhin VV, Collier ML, et al. Venezuelan equine encephalitis virus replicon particles encoding respiratory syncytial virus surface glycoproteins induce protective mucosal responses in mice and cotton rats. J Virol 2007;81:13710–13722.
68. Cano F, Plotnicky-Gilquin H, Nguyen TN, Liljeqvist S, Samuelson P, Bonnefoy J, et al. Partial protection to respiratory syncytial virus (RSV) elicited in mice by intranasal immunization using live staphylococci with surface-displayed RSV-peptides. Vaccine 2000;18:2743–2752.
69. Martinez-Sobrido L, Gitiban N, Fernandez-Sesma A, Cros J, Mertz SE, Jewell NA, et al. Protection against respiratory syncytial virus by a recombinant Newcastle disease virus vector. J Virol 2006;80:1130–1139.
70. Bembridge GP, Rodriguez N, Garcia-Beato R, Nicolson C, Melero JA, Taylor G. Respiratory syncytial virus infection of gene gun vaccinated mice induces Th2-driven pulmonary eosinophilia even in the absence of sensitisation to the fusion (F) or attachment (G) protein. Vaccine 2000;19:1038–1046.
71. Li X, Sambhara S, Li CX, Ewasyshyn M, Parrington M, Caterini J, et al. Protection against respiratory syncytial virus infection by DNA immunization. J Exp Med 1998;188:681–688.
TOOLS
PDF Links  PDF Links
Full text via DOI  Full text via DOI
  via Pubmed
Full text via PMC  Full text via PMC
via Pubreader  via PubReader
Download Citation  Download Citation
Supplementary Material  Supplementary Material
  E-Mail
Share:      
METRICS
1,747
View
9
Download
Association between Kawasaki disease and acute respiratory viral infections  2009 November;52(11)
Clinical usefulness of rapid antigen test to detect respiratory syncytial virus infection  2008 October;51(10)
A Case of Respiratory Syncytial Virus Infection Presented with Apnea  1996 April;39(4)
Clinical and Epidemiologic Features of Respiratory Syncytial Virus Infection  1992 October;35(10)
Register for e-submission
Register here to access the e-submission system of Korean J Pediatr for authors and reviewers.
Manuscript Submission
To submit a manuscript, please visit the Korean J Pediatr e-submission management system at http://submit.kjp.or.kr, read the Instructions for Authors, and log into the Korean J Pediatr e-submission system. For assistance with manuscript submission, please contact: kjpped@gmail.com.
Free archive
Anyone may access any past or current articles without logging in.
Korean Pediatric Society Office
#1606, Seocho World Officetel, 19 Seoun-ro, Seocho-gu, Seoul 137-070, Korea
TEL : +82-2-3473-7305    FAX : +82-2-3473-7307   E-mail: kjpped@gmail.com
BrowseCurrent IssueFor Authors and ReviewersAbout
Copyright© The Korean Pediatric Society. All right reserved.