DNA encoding the attachment (G) or fusion (F) protein of respiratory syncytial virus induces protection in the absence of pulmonary inflammation

Author:

Bembridge Gary P.1,Rodriguez Nuria2,Garcia-Beato Regina2,Nicolson Carolyn3,Melero Jose A.2,Taylor Geraldine1

Affiliation:

1. Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN , UK1

2. Centro Nacional de Biologia Fundamental, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain2

3. NIBSC, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, UK3

Abstract

Significant protection against respiratory syncytial virus (RSV) infection was induced in mice vaccinated intramuscularly (i.m.) with DNA encoding the F or G protein of RSV. The amounts of IgG1 of IgG2a antibodies in mice immunized with DNA-G alone were similar. However, the antibody response in mice co-immunized with DNA-G and DNA encoding IL-4 (DNA-IL-4) was strongly biased towards IgG1. In contrast, the antibody response in mice co-immunized with DNA-G and DNA-IL-2, -IL-12 or-IFN-γ was biased towards IgG2a. Mice vaccinated with DNA-F either alone or in combination with DNA encoding cytokines developed a predominant RSV-specific IgG2a response, which was most pronounced in mice co-immunized with DNA-F and DNA-IL-12 or -IFN-γ. Vaccinated mice developed only a slightly enhanced pulmonary inflammatory response following RSV challenge. More significantly, and in contrast to mice scarified with recombinant vaccinia virus expressing the G protein, mice vaccinated i.m. with DNA-G did not develop pulmonary eosinophilia, even when the immune response was biased towards a Th2 response by co-administration of DNA-IL-4.

Publisher

Microbiology Society

Subject

Virology

Reference23 articles.

1. Distinct patterns of T- and B-cell immunity to respiratory syncytial virus induced by individual viral proteins;Alwan;Vaccine,1993

2. Phenotypic and functional characterization of T cell lines specific for individual respiratory syncytial virus proteins;Alwan;Journal of Immunology,1993

3. Subcellular site of expression and route of vaccination influence pulmonary eosinophilia following respiratory syncytial virus challenge in BALB/c mice sensitized to the attachment G protein;Bembridge;Journal of Immunology,1998 a

4. Recombinant vaccinia virus coexpressing the F protein of respiratory syncytial virus (RSV) and interleukin-4 (IL-4) does not inhibit the development of RSV-specific memory cytotoxic T lymphocytes, whereas priming is diminished in the presence of high levels of IL-2 or gamma interferon;Bembridge;Journal of Virology,1998 b

5. 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;Bembridge;Journal of Virology,1999

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