1887

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Volume 96, Issue 4

Evidence for an intranasal immune response to human respiratory syncytial virus infection in cynomolgus macaques Free

Abstract

There is no large-scale therapy available against human respiratory syncytial virus (hRSV), a major pathogen responsible for acute respiratory diseases. Macaques represent an interesting animal model to evaluate potential treatments because of their genetic, anatomical and immunological proximity with humans. However, the parameters that influence hRSV growth and control in this model are still poorly understood. We have documented in the following study the influence of age as well as repeated infections on the virological, clinical and immunological parameters of this animal model. Following intranasal inoculation, hRSV replicated in the upper respiratory tract for less than 15 days with no clinical signs regardless of age. Interestingly, we observed the induction of a local immune response at the nasal mucosa as assessed by expression profiles of inflammatory and IFN-stimulated genes. Animals also developed specific antibodies and were immune to reinfection. Thus, we showed that even in infant macaques, intranasal hRSV infection induced both local and systemic immune responses to efficiently control the virus.

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© 2015 The Authors
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2015-04-01
2024-04-16
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References

  1. Arai M., Jain S., Weaver A. A., Hill A. A., Guo Y., Bree A. G., Smith M. F. Jr, Allen S. W., LaVallie E. R.other authors 2010; Development and application of a biomarker assay for determining the pharmacodynamic activity of an antagonist candidate biotherapeutic antibody to IL21R in whole blood. J Transl Med 8:51 [View Article][PubMed]
     [Google Scholar]
  2. Babu P. G., Selvan A., Christuraj S., David J., John T. J., Simoes E. A. 1998; A primate model of respiratory syncytial virus infection. Indian J Exp Biol 36:758–762[PubMed]
     [Google Scholar]
  3. Belshe R. B., Richardson L. S., London W. T., Sly D. L., Lorfeld J. H., Camargo E., Prevar D. A., Chanock R. M. 1977; Experimental respiratory syncytial virus infection of four species of primates. J Med Virol 1:157–162 [View Article][PubMed]
     [Google Scholar]
  4. Bem R. A., Domachowske J. B., Rosenberg H. F. 2011; Animal models of human respiratory syncytial virus disease. Am J Physiol Lung Cell Mol Physiol 301:L148–L156 [View Article][PubMed]
     [Google Scholar]
  5. Bermejo-Martin J. F., Garcia-Arevalo M. C., De Lejarazu R. O., Ardura J., Eiros J. M., Alonso A., Matías V., Pino M., Bernardo D.other authors 2007; Predominance of Th2 cytokines, CXC chemokines and innate immunity mediators at the mucosal level during severe respiratory syncytial virus infection in children. Eur Cytokine Netw 18:162–167[PubMed]
     [Google Scholar]
  6. Borchers A. T., Chang C., Gershwin M. E., Gershwin L. J. 2013; Respiratory syncytial virus–a comprehensive review. Clin Rev Allergy Immunol 45:331–379 [View Article][PubMed]
     [Google Scholar]
  7. Byrd L. G., Prince G. A. 1997; Animal models of respiratory syncytial virus infection. Clin Infect Dis 25:1363–1368 [View Article][PubMed]
     [Google Scholar]
  8. Choi J., Callaway Z., Kim H. B., Fujisawa T., Kim C. K. 2010; The role of TNF-alpha in eosinophilic inflammation associated with RSV bronchiolitis. Pediatr Allergy Immunol 21:474–479 [View Article][PubMed]
     [Google Scholar]
  9. Collins P. L., Melero J. A. 2011; Progress in understanding and controlling respiratory syncytial virus: still crazy after all these years. Virus Res 162:80–99 [View Article][PubMed]
     [Google Scholar]
  10. Culley F. J., Pennycook A. M., Tregoning J. S., Dodd J. S., Walzl G., Wells T. N., Hussell T., Openshaw P. J. 2006; Role of CCL5 (RANTES) in viral lung disease. J Virol 80:8151–8157 [View Article][PubMed]
     [Google Scholar]
  11. de Swart R. L., Kuiken T., Timmerman H. H., van Amerongen G., van den Hoogen B. G., Vos H. W., Neijens H. J., Andeweg A. C., Osterhaus A. D. M. E. 2002; Immunization of macaques with formalin-inactivated respiratory syncytial virus (RSV) induces interleukin-13-associated hypersensitivity to subsequent RSV infection. J Virol 76:11561–11569 [View Article][PubMed]
     [Google Scholar]
  12. de Waal L., Power U. F., Yüksel S., van Amerongen G., Nguyen T. N., Niesters H. G., de Swart R. L., Osterhaus A. D. 2004a; Evaluation of BBG2Na in infant macaques: specific immune responses after vaccination and RSV challenge. Vaccine 22:915–922 [View Article][PubMed]
     [Google Scholar]
  13. de Waal L., Wyatt L. S., Yüksel S., van Amerongen G., Moss B., Niesters H. G. M., Osterhaus A. D. M. E., de Swart R. L. 2004b; Vaccination of infant macaques with a recombinant modified vaccinia virus Ankara expressing the respiratory syncytial virus F and G genes does not predispose for immunopathology. Vaccine 22:923–926 [View Article][PubMed]
     [Google Scholar]
  14. DeByle C., Bulkow L., Miernyk K., Chikoyak L., Hummel K. B., Hennessy T., Singleton R. 2012; Comparison of nasopharyngeal flocked swabs and nasopharyngeal wash collection methods for respiratory virus detection in hospitalized children using real-time polymerase chain reaction. J Virol Methods 185:89–93 [View Article][PubMed]
     [Google Scholar]
  15. Fjaerli H. O., Bukholm G., Krog A., Skjaeret C., Holden M., Nakstad B. 2006; Whole blood gene expression in infants with respiratory syncytial virus bronchiolitis. BMC Infect Dis 6:175 [View Article][PubMed]
     [Google Scholar]
  16. Grunwald T., Tenbusch M., Schulte R., Raue K., Wolf H., Hannaman D., de Swart R. L., Uberla K., Stahl-Hennig C. 2014; Novel vaccine regimen elicits strong airway immune responses and control of respiratory syncytial virus in nonhuman primates. J Virol 88:3997–4007 [View Article][PubMed]
     [Google Scholar]
  17. Harrison A. M., Bonville C. A., Rosenberg H. F., Domachowske J. B. 1999; Respiratory syncytical virus-induced chemokine expression in the lower airways: eosinophil recruitment and degranulation. Am J Respir Crit Care Med 159:1918–1924 [View Article][PubMed]
     [Google Scholar]
  18. Heikkinen T., Marttila J., Salmi A. A., Ruuskanen O. 2002; Nasal swab versus nasopharyngeal aspirate for isolation of respiratory viruses. J Clin Microbiol 40:4337–4339 [View Article][PubMed]
     [Google Scholar]
  19. Ioannidis I., McNally B., Willette M., Peeples M. E., Chaussabel D., Durbin J. E., Ramilo O., Mejias A., Flaño E. 2012; Plasticity and virus specificity of the airway epithelial cell immune response during respiratory virus infection. J Virol 86:5422–5436 [View Article][PubMed]
     [Google Scholar]
  20. Krilov L. R. 2011; Respiratory syncytial virus disease: update on treatment and prevention. Expert Rev Anti Infect Ther 9:27–32 [View Article][PubMed]
     [Google Scholar]
  21. McArthur-Vaughan K., Gershwin L. J. 2002; A rhesus monkey model of respiratory syncytial virus infection. J Med Primatol 31:61–73 [View Article][PubMed]
     [Google Scholar]
  22. Murai H., Terada A., Mizuno M., Asai M., Hirabayashi Y., Shimizu S., Morishita T., Kakita H., Hussein M. H.other authors 2007; IL-10 and RANTES are elevated in nasopharyngeal secretions of children with respiratory syncytial virus infection. Allergol Int 56:157–163 [View Article][PubMed]
     [Google Scholar]
  23. Ponnuraj E. M., Hayward A. R., Raj A., Wilson H., Simoes E. A. F. 2001; 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 82:2663–2674[PubMed]
     [Google Scholar]
  24. Scagnolari C., Midulla F., Trombetti S., Pierangeli A., Tromba V., Grossi R., Di Marco P., Dianzani C., Girardi E., Antonelli G. 2007; Upregulation of interferon-induced genes in infants with virus-associated acute bronchiolitis. Exp Biol Med (Maywood) 232:1355–1359 [View Article][PubMed]
     [Google Scholar]
  25. Schmidt A. C., Wenzke D. R., McAuliffe J. M., St Claire M., Elkins W. R., Murphy B. R., Collins P. L. 2002; Mucosal immunization of rhesus monkeys against respiratory syncytial virus subgroups A and B and human parainfluenza virus type 3 by using a live cDNA-derived vaccine based on a host range-attenuated bovine parainfluenza virus type 3 vector backbone. J Virol 76:1089–1099 [View Article][PubMed]
     [Google Scholar]
  26. Schmittgen T. D., Livak K. J. 2008; Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3:1101–1108 [View Article][PubMed]
     [Google Scholar]
  27. Sheeran P., Jafri H., Carubelli C., Saavedra J., Johnson C., Krisher K., Sánchez P. J., Ramilo O. 1999; Elevated cytokine concentrations in the nasopharyngeal and tracheal secretions of children with respiratory syncytial virus disease. Pediatr Infect Dis J 18:115–122 [View Article][PubMed]
     [Google Scholar]
  28. Simoes E. A. F., Hayward A. R., Ponnuraj E. M., Straumanis J. P., Stenmark K. R., Wilson H. L., Babu P. G. 1999; Respiratory syncytial virus infects the Bonnet monkey, Macaca radiata. Pediatr Dev Pathol 2:316–326 [View Article][PubMed]
     [Google Scholar]
  29. Smith K. G., Clatworthy M. R. 2010; FcgammaRIIB in autoimmunity and infection: evolutionary and therapeutic implications. Nat Rev Immunol 10:328–343 [View Article][PubMed]
     [Google Scholar]
  30. van de Pol A. C., Wolfs T. F., van Loon A. M., Tacke C. E., Viveen M. C., Jansen N. J., Kimpen J. L., Rossen J. W., Coenjaerts F. E. 2010; Molecular quantification of respiratory syncytial virus in respiratory samples: reliable detection during the initial phase of infection. J Clin Microbiol 48:3569–3574 [View Article][PubMed]
     [Google Scholar]
  31. Vaughan K., Rhodes G. H., Gershwin L. J. 2005; DNA immunization against respiratory syncytial virus (RSV) in infant rhesus monkeys. Vaccine 23:2928–2942 [View Article][PubMed]
     [Google Scholar]
  32. Weltzin R., Traina-Dorge V., Soike K., Zhang J.-Y., Mack P., Soman G., Drabik G., Monath T. P. 1996; Intranasal monoclonal IgA antibody to respiratory syncytial virus protects rhesus monkeys against upper and lower respiratory tract infection. J Infect Dis 174:256–261 [View Article][PubMed]
     [Google Scholar]
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Evidence for an intranasal immune response to human respiratory syncytial virus infection in cynomolgus macaques
J. Gen. Virol. 96, 782 (2015); https://doi.org/10.1099/vir.0.000039
/content/journal/jgv/10.1099/vir.0.000039
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