Eliminating a region of respiratory syncytial virus attachment protein allows induction of protective immunity without vaccine-enhanced lung eosinophilia

Tim E. Sparer, Stephen Matthews, Tracy Hussell, Aaron J. Rae, Blanca Garcia-Barreno, Jose A. Melero, Peter J M Openshaw

    Research output: Contribution to journalArticlepeer-review

    Abstract

    In a murine model of respiratory syncytial virus disease, prior sensitization to the attachment glycoprotein (G) leads to pulmonary eosinophilia and enhanced illness. Three different approaches were taken to dissect the region of G responsible for cnhanced disease and protection against challenge. First, mutant viruses, containing frameshifts that altered the COOH terminus of the G protein, were used to challenge mice sensitized by scarification with recombinant vaccinia virus (rVV) expressing wild-type G. Second, cDNA expressing these mutated G proteins were expressed by rVV and used to vaccinate mice before challenge with wild-type respiratory syncytial virus (RSV). These studies identified residues 193-205 to be responsible for G-induced weight loss and lung eosinophilia and showed that this region was not was not necessary for induction of protective immunity. Third, mice were sensitized using all rVV that expressed only amino acids 124-203 of the G protein. Upon RSV challenge, mice sensitized with this rVV developed enhanced weight loss and eosinophilia. This is the first time that a region within RSV (amino acids 193-203) has been shown to be responsible for induction of lung eosinophilia and disease enhancement. Moreover, we now show that it is possible to induce protective immunity with an altered G protein without inducing a pathological response.
    Original languageEnglish
    Pages (from-to)1921-1926
    Number of pages5
    JournalJournal of Experimental Medicine
    Volume187
    Issue number11
    DOIs
    Publication statusPublished - 1 Jun 1998

    Keywords

    • Eosinophilia
    • G protein
    • Respiratory syncytial virus
    • T helper cell
    • Vaccine

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