Murine host responses to respiratory syncytial virus (RSV) following intranasal administration of a Protollin-adjuvanted, epitope-enhanced recombinant G protein vaccine.
BACKGROUND
Immunization of mice with the G protein of respiratory syncytial virus (RSV) characteristically induces an immune response that is partially protective, but which can prime for pulmonary eosinophilia. We have shown previously that the N191A mutation in a recombinant RSV G protein fragment is associated with reduced pulmonary eosinophilic infiltration when administered with alum subcutaneously in BALB/c mice followed by RSV challenge. We hypothesize that the performance of this "epitope enhanced" recombinant G protein fragment may be further improved by combining with the newly developed adjuvant, Protollin, coupled with intranasal delivery.


OBJECTIVE
To investigate efficacy of an intranasally delivered, Protollin-adjuvanted, epitope-enhanced recombinant G protein vaccine in BALB/c mice.


METHODS
Recombinant protein, designated Trx-G128-229, consisted of a bacterially expressed central fragment (amino acids 128-229) of the RSV Long strain G protein fused to a fragment of thioredoxin (Trx). BALB/c mice were chosen to evaluate the effectiveness of wild type and epitope-enhanced Trx-G128-229 as a nasal vaccine with the adjuvant Protollin.


RESULTS
The intranasal administration of Trx-G128-229 with Protollin conferred similar protection against RSV challenge as subcutaneously administered Trx-G128-229 with alum, but with markedly reduced eosinophilia and the Th2 cytokine IL-13.


CONCLUSIONS
These results support the concept of an RSV vaccine optimized by combined strategies, including epitope enhancement and judicious selection of adjuvants.
Huang
Yan
Y
Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, Canada. robert.anderson@dal.ca
Cyr
Sonya L
SL
Burt
David S
DS
Anderson
Robert
R
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003546:Cysteine Endopeptidases / Q000008:administration & dosage* / Q000494:pharmacology; D004338:Drug Combinations; D004802:Eosinophilia / Q000517:prevention & control; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004338:Drug Combinations; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; C493785:Protollin; D022261:Respiratory Syncytial Virus Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C116204:attachment protein G; D003546:Cysteine Endopeptidases