1887

Abstract

Human metapneumovirus (hMPV) and respiratory syncytial virus, its close family member, are two major causes of lower respiratory tract infection in the paediatric population. hMPV is also a common cause of worldwide morbidity and mortality in immunocompromised patients and older adults. Repeated infections occur often, demonstrating a heavy medical burden. However, there is currently no hMPV-specific prevention treatment. This review focuses on the current literature on hMPV vaccine development. We believe that a better understanding of the role(s) of viral proteins in host responses might lead to efficient prophylactic vaccine development.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.000083
2015-07-01
2019-12-15
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/7/1515.html?itemId=/content/journal/jgv/10.1099/vir.0.000083&mimeType=html&fmt=ahah

References

  1. Anderson L. J., Dormitzer P. R., Nokes D. J., Rappuoli R., Roca A., Graham B. S.. ( 2013; ). Strategic priorities for respiratory syncytial virus (RSV) vaccine development. . Vaccine 31: (Suppl 2), B209–B215. [CrossRef] [PubMed]
    [Google Scholar]
  2. Bao X., Kolli D., Liu T., Shan Y., Garofalo R. P., Casola A.. ( 2008; a). Human metapneumovirus small hydrophobic protein inhibits NF-kappaB transcriptional activity. . J Virol 82:, 8224–8229. [CrossRef] [PubMed]
    [Google Scholar]
  3. Bao X., Liu T., Shan Y., Li K., Garofalo R. P., Casola A.. ( 2008; b). Human metapneumovirus glycoprotein G inhibits innate immune responses. . PLoS Pathog 4:, e1000077. [CrossRef] [PubMed]
    [Google Scholar]
  4. Bao X., Kolli D., Ren J., Liu T., Garofalo R. P., Casola A.. ( 2013; ). Human metapneumovirus glycoprotein G disrupts mitochondrial signaling in airway epithelial cells. . PLoS ONE 8:, e62568. [CrossRef] [PubMed]
    [Google Scholar]
  5. Becker Y.. ( 2006; ). Respiratory syncytial virus (RSV) evades the human adaptive immune system by skewing the Th1/Th2 cytokine balance toward increased levels of Th2 cytokines and IgE, markers of allergy–a review. . Virus Genes 33:, 235–252.[PubMed]
    [Google Scholar]
  6. Bermingham A., Collins P. L.. ( 1999; ). 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 U S A 96:, 11259–11264. [CrossRef] [PubMed]
    [Google Scholar]
  7. Biacchesi S., Skiadopoulos M. H., Tran K. C., Murphy B. R., Collins P. L., Buchholz U. J.. ( 2004; a). Recovery of human metapneumovirus from cDNA: optimization of growth in vitro and expression of additional genes. . Virology 321:, 247–259. [CrossRef] [PubMed]
    [Google Scholar]
  8. Biacchesi S., Skiadopoulos M. H., Yang L., Lamirande E. W., Tran K. C., Murphy B. R., Collins P. L., Buchholz U. J.. ( 2004; b). Recombinant human metapneumovirus lacking the small hydrophobic SH and/or attachment G glycoprotein: deletion of G yields a promising vaccine candidate. . J Virol 78:, 12877–12887. [CrossRef] [PubMed]
    [Google Scholar]
  9. Biacchesi S., Pham Q. N., Skiadopoulos M. H., Murphy B. R., Collins P. L., Buchholz U. J.. ( 2005; ). Infection of nonhuman primates with recombinant human metapneumovirus lacking the SH, G, or M2-2 protein categorizes each as a nonessential accessory protein and identifies vaccine candidates. . J Virol 79:, 12608–12613. [CrossRef] [PubMed]
    [Google Scholar]
  10. Boelen A., Andeweg A., Kwakkel J., Lokhorst W., Bestebroer T., Dormans J., Kimman T.. ( 2000; ). Both immunisation with a formalin-inactivated respiratory syncytial virus (RSV) vaccine and a mock antigen vaccine induce severe lung pathology and a Th2 cytokine profile in RSV-challenged mice. . Vaccine 19:, 982–991. [CrossRef] [PubMed]
    [Google Scholar]
  11. Buchholz U. J., Biacchesi S., Pham Q. N., Tran K. C., Yang L., Luongo C. L., Skiadopoulos M. H., Murphy B. R., Collins P. L.. ( 2005; ). Deletion of M2 gene open reading frames 1 and 2 of human metapneumovirus: effects on RNA synthesis, attenuation, and immunogenicity. . J Virol 79:, 6588–6597. [CrossRef] [PubMed]
    [Google Scholar]
  12. Cox R. G., Erickson J. J., Hastings A. K., Becker J. C., Johnson M., Craven R. E., Tollefson S. J., Boyd K. L., Williams J. V.. ( 2014; ). Human metapneumovirus virus-like particles induce protective B and T cell responses in a mouse model. . J Virol 88:, 6368–6379. [CrossRef] [PubMed]
    [Google Scholar]
  13. Crowe J. E. Jr, Bui P. T., Siber G. R., Elkins W. R., Chanock R. M., Murphy B. R.. ( 1995; ). Cold-passaged, temperature-sensitive mutants of human respiratory syncytial virus (RSV) are highly attenuated, immunogenic, and protective in seronegative chimpanzees, even when RSV antibodies are infused shortly before immunization. . Vaccine 13:, 847–855. [CrossRef] [PubMed]
    [Google Scholar]
  14. Delgado M. F., Coviello S., Monsalvo A. C., Melendi G. A., Hernandez J. Z., Batalle J. P., Diaz L., Trento A., Chang H. Y. et al. ( 2009; ). Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease. . Nat Med 15:, 34–41. [CrossRef] [PubMed]
    [Google Scholar]
  15. Deng J., Ptashkin R. N., Wang Q., Liu G., Zhang G., Lee I., Lee Y. S., Bao X.. ( 2014; ). Human metapneumovirus infection induces significant changes in small noncoding RNA expression in airway epithelial cells. . Mol Ther Nucleic Acids 3:, e163. [CrossRef] [PubMed]
    [Google Scholar]
  16. Driscoll, F. W. (2013). Novavax Reports Positive Top-Line Results From Phase II ClinicalTrial of RSV Vaccine Candidate in Women of Childbearing Age. (http://www.novavax.com/download/releases/Novavax%20RSV%20WCBA%20Phase%20II-Final%204%202%2013.pdf)
  17. Edwards K. M., Zhu Y., Griffin M. R., Weinberg G. A., Hall C. B., Szilagyi P. G., Staat M. A., Iwane M., Prill M. M., Williams J. V..New Vaccine Surveillance Network ( 2013; ). Burden of human metapneumovirus infection in young children. . N Engl J Med 368:, 633–643. [CrossRef] [PubMed]
    [Google Scholar]
  18. Englund J. A., Boeckh M., Kuypers J., Nichols W. G., Hackman R. C., Morrow R. A., Fredricks D. N., Corey L.. ( 2006; ). Brief communication: fatal human metapneumovirus infection in stem-cell transplant recipients. . Ann Intern Med 144:, 344–349. [CrossRef] [PubMed]
    [Google Scholar]
  19. Esper F., Martinello R. A., Boucher D., Weibel C., Ferguson D., Landry M. L., Kahn J. S.. ( 2004; ). A 1-year experience with human metapneumovirus in children aged <5 years. . J Infect Dis 189:, 1388–1396. [CrossRef] [PubMed]
    [Google Scholar]
  20. Falsey A. R., Erdman D., Anderson L. J., Walsh E. E.. ( 2003; ). Human metapneumovirus infections in young and elderly adults. . J Infect Dis 187:, 785–790. [CrossRef] [PubMed]
    [Google Scholar]
  21. Gaunt E. R., Jansen R. R., Poovorawan Y., Templeton K. E., Toms G. L., Simmonds P.. ( 2011; ). Molecular epidemiology and evolution of human respiratory syncytial virus and human metapneumovirus. . PLoS ONE 6:, e17427. [CrossRef] [PubMed]
    [Google Scholar]
  22. Goutagny N., Jiang Z., Tian J., Parroche P., Schickli J., Monks B. G., Ulbrandt N., Ji H., Kiener P. A. et al. ( 2010; ). Cell type-specific recognition of human metapneumoviruses (HMPVs) by retinoic acid-inducible gene I (RIG-I) and TLR7 and viral interference of RIG-I ligand recognition by HMPV-B1 phosphoprotein. . J Immunol 184:, 1168–1179. [CrossRef] [PubMed]
    [Google Scholar]
  23. Hamelin M. E., Couture C., Sackett M. K., Boivin G.. ( 2007; ). Enhanced lung disease and Th2 response following human metapneumovirus infection in mice immunized with the inactivated virus. . J Gen Virol 88:, 3391–3400. [CrossRef] [PubMed]
    [Google Scholar]
  24. Herd K. A., Mahalingam S., Mackay I. M., Nissen M., Sloots T. P., Tindle R. W.. ( 2006; ). Cytotoxic T-lymphocyte epitope vaccination protects against human metapneumovirus infection and disease in mice. . J Virol 80:, 2034–2044. [CrossRef] [PubMed]
    [Google Scholar]
  25. Herfst S., de Graaf M., Schrauwen E. J., Sprong L., Hussain K., van den Hoogen B. G., Osterhaus A. D., Fouchier R. A.. ( 2008; a). Generation of temperature-sensitive human metapneumovirus strains that provide protective immunity in hamsters. . J Gen Virol 89:, 1553–1562. [CrossRef] [PubMed]
    [Google Scholar]
  26. Herfst S., Schrauwen E. J., de Graaf M., van Amerongen G., van den Hoogen B. G., de Swart R. L., Osterhaus A. D., Fouchier R. A.. ( 2008; b). Immunogenicity and efficacy of two candidate human metapneumovirus vaccines in cynomolgus macaques. . Vaccine 26:, 4224–4230. [CrossRef] [PubMed]
    [Google Scholar]
  27. Hussell T., Baldwin C. J., O’Garra A., Openshaw P. J. M.. ( 1997; ). CD8+ T cells control Th2-driven pathology during pulmonary respiratory syncytial virus infection. . Eur J Immunol 27:, 3341–3349. [CrossRef] [PubMed]
    [Google Scholar]
  28. Juhasz K., Whitehead S. S., Bui P. T., Biggs J. M., Crowe J. E., Boulanger C. A., Collins P. L., Murphy B. R.. ( 1997; ). The temperature-sensitive (ts) phenotype of a cold-passaged (cp) live attenuated respiratory syncytial virus vaccine candidate, designated cpts530, results from a single amino acid substitution in the L protein. . J Virol 71:, 5814–5819.[PubMed]
    [Google Scholar]
  29. Kapikian A. Z., Mitchell R. H., Chanock R. M., Shvedoff R. A., Stewart C. E.. ( 1969; ). 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 89:, 405–421.[PubMed]
    [Google Scholar]
  30. Kim H. W., Canchola J. G., Brandt C. D., Pyles G., Chanock R. M., Jensen K., Parrott R. H.. ( 1969; ). Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. . Am J Epidemiol 89:, 422–434.[PubMed]
    [Google Scholar]
  31. Kitagawa Y., Zhou M., Yamaguchi M., Komatsu T., Takeuchi K., Itoh M., Gotoh B.. ( 2010; ). Human metapneumovirus M2-2 protein inhibits viral transcription and replication. . Microbes Infect 12:, 135–145. [CrossRef] [PubMed]
    [Google Scholar]
  32. Kolli D., Bao X., Liu T., Hong C., Wang T., Garofalo R. P., Casola A.. ( 2011; ). Human metapneumovirus glycoprotein G inhibits TLR4-dependent signaling in monocyte-derived dendritic cells. . J Immunol 187:, 47–54. [CrossRef] [PubMed]
    [Google Scholar]
  33. Lévy C., Aerts L., Hamelin M. E., Granier C., Szécsi J., Lavillette D., Boivin G., Cosset F. L.. ( 2013; ). Virus-like particle vaccine induces cross-protection against human metapneumovirus infections in mice. . Vaccine 31:, 2778–2785. [CrossRef] [PubMed]
    [Google Scholar]
  34. Lindell D. M., Morris S. B., White M. P., Kallal L. E., Lundy P. K., Hamouda T., Baker J. R. Jr, Lukacs N. W.. ( 2011; ). A novel inactivated intranasal respiratory syncytial virus vaccine promotes viral clearance without Th2 associated vaccine-enhanced disease. . PLoS ONE 6:, e21823. [CrossRef] [PubMed]
    [Google Scholar]
  35. Melendi G. A., Zavala F., Buchholz U. J., Boivin G., Collins P. L., Kleeberger S. R., Polack F. P.. ( 2007; ). Mapping and characterization of the primary and anamnestic H-2 (d)-restricted cytotoxic T-lymphocyte response in mice against human metapneumovirus. . J Virol 81:, 11461–11467. [CrossRef] [PubMed]
    [Google Scholar]
  36. Moghaddam A., Olszewska W., Wang B., Tregoning J. S., Helson R., Sattentau Q. J., Openshaw P. J.. ( 2006; ). A potential molecular mechanism for hypersensitivity caused by formalin-inactivated vaccines. . Nat Med 12:, 905–907. [CrossRef] [PubMed]
    [Google Scholar]
  37. Mok H., Tollefson S. J., Podsiad A. B., Shepherd B. E., Polosukhin V. V., Johnston R. E., Williams J. V., Crowe J. E. Jr. ( 2008; ). An alphavirus replicon-based human metapneumovirus vaccine is immunogenic and protective in mice and cotton rats. . J Virol 82:, 11410–11418. [CrossRef] [PubMed]
    [Google Scholar]
  38. Mukherjee S., Lindell D. M., Berlin A. A., Morris S. B., Shanley T. P., Hershenson M. B., Lukacs N. W.. ( 2011; ). IL-17-induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease. . Am J Pathol 179:, 248–258. [CrossRef] [PubMed]
    [Google Scholar]
  39. Openshaw P. J., Clarke S. L., Record F. M.. ( 1992; ). Pulmonary eosinophilic response to respiratory syncytial virus infection in mice sensitized to the major surface glycoprotein G. . Int Immunol 4:, 493–500. [CrossRef] [PubMed]
    [Google Scholar]
  40. Palavecino C. E., Céspedes P. F., Gómez R. S., Kalergis A. M., Bueno S. M.. ( 2014; ). Immunization with a recombinant bacillus Calmette-Guerin strain confers protective Th1 immunity against the human metapneumovirus. . J Immunol 192:, 214–223. [CrossRef] [PubMed]
    [Google Scholar]
  41. Papenburg J., Carbonneau J., Isabel S., Bergeron M. G., Williams J. V., De Serres G., Hamelin M. E., Boivin G.. ( 2013; ). Genetic diversity and molecular evolution of the major human metapneumovirus surface glycoproteins over a decade. . J Clin Virol 58:, 541–547. [CrossRef] [PubMed]
    [Google Scholar]
  42. Pham Q. N., Biacchesi S., Skiadopoulos M. H., Murphy B. R., Collins P. L., Buchholz U. J.. ( 2005; ). Chimeric recombinant human metapneumoviruses with the nucleoprotein or phosphoprotein open reading frame replaced by that of avian metapneumovirus exhibit improved growth in vitro and attenuation in vivo. . J Virol 79:, 15114–15122. [CrossRef] [PubMed]
    [Google Scholar]
  43. Ren J., Wang Q., Kolli D., Prusak D. J., Tseng C. T., Chen Z. J., Li K., Wood T. G., Bao X.. ( 2012; ). Human metapneumovirus M2-2 protein inhibits innate cellular signaling by targeting MAVS. . J Virol 86:, 13049–13061. [CrossRef] [PubMed]
    [Google Scholar]
  44. Ren J., Liu G., Go J., Kolli D., Zhang G., Bao X.. ( 2014; ). Human metapneumovirus M2-2 protein inhibits innate immune response in monocyte-derived dendritic cells. . PLoS ONE 9:, e91865. [CrossRef] [PubMed]
    [Google Scholar]
  45. Rey G. U., Miao C., Caidi H., Trivedi S. U., Harcourt J. L., Tripp R. A., Anderson L. J., Haynes L. M.. ( 2013; ). Decrease in formalin-inactivated respiratory syncytial virus (FI-RSV) enhanced disease with RSV G glycoprotein peptide immunization in BALB/c mice. . PLoS ONE 8:, e83075. [CrossRef] [PubMed]
    [Google Scholar]
  46. Ryder A. B., Tollefson S. J., Podsiad A. B., Johnson J. E., Williams J. V.. ( 2010; ). Soluble recombinant human metapneumovirus G protein is immunogenic but not protective. . Vaccine 28:, 4145–4152. [CrossRef] [PubMed]
    [Google Scholar]
  47. Schickli J. H., Kaur J., Macphail M., Guzzetta J. M., Spaete R. R., Tang R. S.. ( 2008; ). Deletion of human metapneumovirus M2-2 increases mutation frequency and attenuates growth in hamsters. . Virol J 5:, 69. [CrossRef] [PubMed]
    [Google Scholar]
  48. Schildgen V., van den Hoogen B., Fouchier R., Tripp R. A., Alvarez R., Manoha C., Williams J., Schildgen O.. ( 2011; ). Human metapneumovirus: lessons learned over the first decade. . Clin Microbiol Rev 24:, 734–754. [CrossRef] [PubMed]
    [Google Scholar]
  49. Schmidt A. C.. ( 2011; ). Progress in respiratory virus vaccine development. . Semin Respir Crit Care Med 32:, 527–540. [CrossRef] [PubMed]
    [Google Scholar]
  50. Skiadopoulos M. H., Biacchesi S., Buchholz U. J., Amaro-Carambot E., Surman S. R., Collins P. L., Murphy B. R.. ( 2006; ). Individual contributions of the human metapneumovirus F, G, and SH surface glycoproteins to the induction of neutralizing antibodies and protective immunity. . Virology 345:, 492–501. [CrossRef] [PubMed]
    [Google Scholar]
  51. Talaat K. R., Karron R. A., Thumar B., McMahon B. A., Schmidt A. C., Collins P. L., Buchholz U. J.. ( 2013; ). Experimental infection of adults with recombinant wild-type human metapneumovirus. . J Infect Dis 208:, 1669–1678. [CrossRef] [PubMed]
    [Google Scholar]
  52. Tang R. S., Mahmood K., Macphail M., Guzzetta J. M., Haller A. A., Liu H., Kaur J., Lawlor H. A., Stillman E. A. et al. ( 2005; ). A host-range restricted parainfluenza virus type 3 (PIV3) expressing the human metapneumovirus (hMPV) fusion protein elicits protective immunity in African green monkeys. . Vaccine 23:, 1657–1667. [CrossRef] [PubMed]
    [Google Scholar]
  53. van den Hoogen B. G., de Jong J. C., Groen J., Kuiken T., de Groot R., Fouchier R. A., Osterhaus A. D.. ( 2001; ). A newly discovered human pneumovirus isolated from young children with respiratory tract disease. . Nat Med 7:, 719–724. [CrossRef] [PubMed]
    [Google Scholar]
  54. van den Hoogen B. G., Bestebroer T. M., Osterhaus A. D., Fouchier R. A.. ( 2002; ). Analysis of the genomic sequence of a human metapneumovirus. . Virology 295:, 119–132. [CrossRef] [PubMed]
    [Google Scholar]
  55. Whitehead S. S., Juhasz K., Firestone C. Y., Collins P. L., Murphy B. R.. ( 1998; ). Recombinant respiratory syncytial virus (RSV) bearing a set of mutations from cold-passaged RSV is attenuated in chimpanzees. . J Virol 72:, 4467–4471.[PubMed]
    [Google Scholar]
  56. Wright P. F., Karron R. A., Belshe R. B., Thompson J., Crowe J. E. Jr, Boyce T. G., Halburnt L. L., Reed G. W., Whitehead S. S. et al. ( 2000; ). Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy. . J Infect Dis 182:, 1331–1342. [CrossRef] [PubMed]
    [Google Scholar]
  57. Yang C. F., Wang C. K., Malkin E., Schickli J. H., Shambaugh C., Zuo F., Galinski M. S., Dubovsky F., Tang R. S..Study Group ( 2013; ). Implication of respiratory syncytial virus (RSV) F transgene sequence heterogeneity observed in Phase 1 evaluation of MEDI-534, a live attenuated parainfluenza type 3 vectored RSV vaccine. . Vaccine 31:, 2822–2827. [CrossRef] [PubMed]
    [Google Scholar]
  58. Yim K. C., Cragin R. P., Boukhvalova M. S., Blanco J. C., Hamlin M. E., Boivin G., Porter D. D., Prince G. A.. ( 2007; ). Human metapneumovirus: enhanced pulmonary disease in cotton rats immunized with formalin-inactivated virus vaccine and challenged. . Vaccine 25:, 5034–5040. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.000083
Loading

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error