Modulation of protective immunity, eosinophilia, and cytokine responses by selective mutagenesis of a recombinant G protein vaccine against respiratory syncytial virus.
Using an Escherichia coli-grown plasmid vector encoding a fragment of thioredoxin (Trx) fused to a central region (amino acids 128 to 229) of the respiratory syncytial virus (RSV) (Long strain) G protein, we employed site-directed mutagenesis to investigate the importance of selected amino acids to vaccine efficacy. Mice were immunized with a total of 10 wild-type or mutant Trx-G proteins and challenged intranasally with RSV. Striking differences in the induction of RSV G-protein-specific antibodies, protection against RSV challenge, cytokine RNA responses, and induction of RSV-associated eosinophilic inflammation were observed among the mutant proteins examined. Taken together, the results identify a critical role for specific amino acids in the induction of protective immunity and priming for eosinophilia against RSV.
Huang
Yan
Y
Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada.
Anderson
Robert
R
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004802:Eosinophilia; D008168:Lung / Q000276:immunology; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000235:genetics / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000914:Antibodies, Viral; D016207:Cytokines; D012333:RNA, Messenger; D022261:Respiratory Syncytial Virus Vaccines; D014614:Vaccines, Synthetic; D014764:Viral Proteins; C041524:aluminum sulfate