Immunogenicity and efficacy of recombinant RSV-F vaccine in a mouse model

RSV vaccine development has constraints due to safety issues encountered by formalin-inactivated FI-RSV vaccines. A desirable vaccine should induce Th1 responses and a strong mucosal immunity to provide complete protection from RSV infection. In the present paper, we developed and evaluated a mucosal vaccine against RSV in a mouse model. The antigenic regions corresponding to residues 412–524 of RSV-F protein were amplified by RT-PCR and cloned into a vector containing the ctxA2B gene of the cholera toxin. The recombinant protein was expressed in E. coli and properties of the recombinant protein were analyzed by SDS-PAGE, Western blot and GM1-ELISA. The purified recombinant protein (rRF-412) was used to immunize BALB/c mice intranasally. The results from our studies show that the rRF-412 immunogen induced mucosal (IgA) and systemic antibody (IgG, IgG1, IgG2a, and IgG2b) responses which neutralized RSV. The IgG1/IgG2a ratios indicated a Th1-biased antibody response. The Th1 (TNF-α, IL-12p70, IFN-γ, IL-2) and Th2 (IL-10, IL-4 and IL-5) cytokine profiles were analyzed after stimulation of spleen cells from mice immunized with purified RF-412 protein. Similar to the antibody response, we observed that the rRF-412 immunogen induced a mixed Th1/Th2 cytokine immune response with a Th1-bias response. Serum antibodies were capable of neutralizing RSV and mice immunized with rRF-412 were significantly protected from live RSV challenge. Our data provides evidence that the rRF-412 immunogen may be a potential mucosal vaccine candidate against RSV.