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Journal of Virology, December 1999, p. 10086-10094, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Priming with a Secreted Form of the Fusion Protein of Respiratory Syncytial Virus (RSV) Promotes Interleukin-4 (IL-4) and IL-5 Production but Not Pulmonary Eosinophilia following RSV Challenge

Gary P. Bembridge,1,* Juan A. Lopez,2 Regla Bustos,2 Jose A. Melero,2 Roy Cook,1 Helen Mason,1 and Geraldine Taylor1

Institute for Animal Health, Compton, Newbury RG20 7NN, United Kingdom,1 and Centro Nacional de Biologia Celular y Retrovirus, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain2

Received 19 May 1999/Accepted 7 September 1999

The attachment (G) protein of respiratory syncytial virus (RSV) is synthesized as two mature forms: a membrane-anchored form and a smaller secreted form. BALB/c mice scarified with vaccinia virus (VV) expressing the secreted form develop a greater pulmonary eosinophilic influx following RSV challenge than do mice scarified with VV expressing the membrane-anchored form. To determine if a soluble form of an RSV protein was sufficient to induce eosinophilia following RSV challenge, a cDNA that encoded a secreted form of the fusion (F) protein of RSV was constructed and expressed in VV (VV-Ftm-). Splenocytes and lung lymphocytes from mice primed with VV-Ftm- produced significantly more of the Th2 cytokines interleukin-4 (IL-4) and IL-5 than did mice vaccinated with VV expressing either the native (membrane-anchored) form of the F protein or the G protein. Although mice scarified with VV-Ftm- developed a slight increase in the number of pulmonary eosinophils following RSV infection, the increase was not as great as that seen in VV-G-primed mice. Despite the increased IL-4 and IL-5 production and in contrast to mice primed with VV-G, mice primed with VV-Ftm- developed RSV-specific cytotoxic T lymphocytes (CTL) and maintained high levels of gamma interferon production. These data demonstrate that recombinant VV strains expressing soluble forms of RSV proteins induce immune responses that are more Th2-like. However, this change alone does not appear sufficient to induce vaccine-augmented disease in the face of active CD8+ CTL populations.

* Corresponding author. Mailing address: Institute for Animal Health, Compton, Newbury RG20 7NN, United Kingdom. Phone: 1635 578411. Fax: 1635 577263. E-mail: Gary.Bembridge{at}bbsrc.ac.uk.

Journal of Virology, December 1999, p. 10086-10094, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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