This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Power, U. F.
Right arrow Articles by Nguyen, T. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Power, U. F.
Right arrow Articles by Nguyen, T. N.

 Previous Article  |  Next Article 

Journal of Virology, December 2001, p. 12421-12430, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.12421-12430.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Differential Histopathology and Chemokine Gene Expression in Lung Tissues following Respiratory Syncytial Virus (RSV) Challenge of Formalin-Inactivated RSV- or BBG2Na-Immunized Mice

Ultan F. Power,* Thierry Huss,dagger Vincent Michaud, Hélène Plotnicky-Gilquin, Jean-Yves Bonnefoy, and Thien Ngoc Nguyen

Centre d'Immunologie Pierre Fabre, 74164 Saint-Julien-en-Genevois, France

Received 1 November 1999/Accepted 10 August 2001

A BALB/c mouse model of enhanced pulmonary pathology following vaccination with formalin-inactivated alum-adsorbed respiratory syncytial virus (FI-RSV) and live RSV challenge was used to determine the type and kinetics of histopathologic lesions induced and chemokine gene expression profiles in lung tissues. These data were compared and contrasted with data generated following primary and/or secondary RSV infection or RSV challenge following vaccination with a promising subunit vaccine, BBG2Na. Severe peribronchiolitis and perivascularitis coupled with alveolitis and interstitial inflammation were the hallmarks of lesions in the lungs of FI-RSV-primed mice, with peak histopathology evident on days 5 and 9. In contrast, primary RSV infection resulted in no discernible lesions, while challenge of RSV-primed mice resulted in rare but mild peribronchiolitis and perivascularitis, with no evidence of alveolitis or interstitial inflammation. Importantly, mice vaccinated with a broad dose range (20 to 0.02 µg) of a clinical formulation of BBG2Na in aluminium phosphate demonstrated histopathology similar to that observed in secondary RSV infection. At the molecular level, FI-RSV priming was characterized by a rapid and strong up-regulation of eotaxin and monocyte chemotactic protein 3 (MCP-3) relative gene expression (potent lymphocyte and eosinophil chemoattractants) that was sustained through late time points, early but intermittent up-regulation of GRO/melanoma growth stimulatory activity gene and inducible protein 10 gene expression, while macrophage inflammatory protein 2 (MIP-2) and especially MCP-1 were up-regulated only at late time points. By comparison, primary RSV infection or BBG2Na priming resulted in considerably lower eotaxin and MCP-3 gene expression increases postchallenge, while expression of lymphocyte or monocyte chemoattractant chemokine genes (MIP-1beta , MCP-1, and MIP-2) were of higher magnitude and kinetics at early, but not late, time points. Our combined histopathologic and chemokine gene expression data provide a basis for differentiating between aberrant FI-RSV-induced immune responses and normal responses associated with RSV infection in the mouse model. Consequently, our data suggest that BBG2Na may constitute a safe RSV subunit vaccine for use in seronegative infants.

* Corresponding author. Mailing address: Centre d'Immunologie Pierre Fabre, 5 av. Napoléon III, 74164 Saint-Julien-en-Genevois, France. Phone: (33)450.35.35.55. Fax: (33)450.35.35.90. E-mail: ultan.power{at}pierre-fabre.com.

dagger Present address: Transgène S.A., 67082 Strasbourg Cedex, France.

Journal of Virology, December 2001, p. 12421-12430, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.12421-12430.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Santiago, J., Hernandez-Cruz, J. L., Manjarrez-Zavala, M. E., Montes-Vizuet, R., Rosete-Olvera, D. P., Tapia-Diaz, A. M., Zepeda-Peney, H., Teran, L. M. (2008). Role of monocyte chemotactic protein-3 and -4 in children with virus exacerbation of asthma. Eur Respir J 32: 1243-1942 [Abstract] [Full Text]  
  • Davis, I. C., Xu, A., Gao, Z., Hickman-Davis, J. M., Factor, P., Sullender, W. M., Matalon, S. (2007). Respiratory syncytial virus induces insensitivity to beta-adrenergic agonists in mouse lung epithelium in vivo. Am. J. Physiol. Lung Cell. Mol. Physiol. 293: L281-L289 [Abstract] [Full Text]  
  • Martinez, I., Lombardia, L., Garcia-Barreno, B., Dominguez, O., Melero, J. A. (2007). Distinct gene subsets are induced at different time points after human respiratory syncytial virus infection of A549 cells. J. Gen. Virol. 88: 570-581 [Abstract] [Full Text]  
  • Niimi, K., Asano, K., Shiraishi, Y., Nakajima, T., Wakaki, M., Kagyo, J., Takihara, T., Suzuki, Y., Fukunaga, K., Shiomi, T., Oguma, T., Sayama, K., Yamaguchi, K., Natori, Y., Matsumoto, M., Seya, T., Yamaya, M., Ishizaka, A. (2007). TLR3-Mediated Synthesis and Release of Eotaxin-1/CCL11 from Human Bronchial Smooth Muscle Cells Stimulated with Double-Stranded RNA. J. Immunol. 178: 489-495 [Abstract] [Full Text]  
  • Hausmann, M., Bataille, F., Spoettl, T., Schreiter, K., Falk, W., Schoelmerich, J., Herfarth, H., Rogler, G. (2005). Physiological Role of Macrophage Inflammatory Protein-3{alpha} Induction during Maturation of Intestinal Macrophages. J. Immunol. 175: 1389-1398 [Abstract] [Full Text]  
  • Huang, Y., Anderson, R. (2005). Modulation of Protective Immunity, Eosinophilia, and Cytokine Responses by Selective Mutagenesis of a Recombinant G Protein Vaccine against Respiratory Syncytial Virus. J. Virol. 79: 4527-4532 [Abstract] [Full Text]  
  • Chen, M., Hu, K.-F., Rozell, B., Orvell, C., Morein, B., Liljestrom, P. (2002). Vaccination with Recombinant Alphavirus or Immune-Stimulating Complex Antigen Against Respiratory Syncytial Virus. J. Immunol. 169: 3208-3216 [Abstract] [Full Text]  
  • Plotnicky-Gilquin, H., Cyblat-Chanal, D., Aubry, J.-P., Champion, T., Beck, A., Nguyen, T., Bonnefoy, J.-Y., Corvaia, N. (2002). Gamma Interferon-Dependent Protection of the Mouse Upper Respiratory Tract following Parenteral Immunization with a Respiratory Syncytial Virus G Protein Fragment. J. Virol. 76: 10203-10210 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»