Murine host responses to respiratory syncytial virus (RSV) following intranasal administration of a Protollin-adjuvanted, epitope-enhanced recombinant G protein vaccine

Abstract

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.

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

Study design: 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.