Eliminating a region of respiratory syncytial virus attachment protein allows induction of protective immunity without vaccine-enhanced lung eosinophilia.
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 enhanced 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 an 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.
Sparer
T E
TE
Imperial College School of Medicine, National Heart and Lung Institute at St. Mary's, London, W2 1PG United Kingdom.
Matthews
S
S
Hussell
T
T
Rae
A J
AJ
Garcia-Barreno
B
B
Melero
J A
JA
Openshaw
P J
PJ
D000818:Animals; D002874:Chromosome Mapping; D004802:Eosinophilia / Q000139:chemically induced*; D005260:Female; D015707:HN Protein; D006801:Humans; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016296:Mutagenesis; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*; D015431:Weight Loss
D015707:HN Protein; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C116204:attachment protein G