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 Th(1) 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 ctxA(2)B 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 G(M1)-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 Th(1)-biased antibody response. The Th(1) (TNF-alpha, IL-12p70, IFN-gamma, IL-2) and Th(2) (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 Th(1)/Th(2) cytokine immune response with a Th(1)-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.
Singh
Shree R
SR
Department of Mathematics and Science, Alabama State University, Montgomery, AL 36104, USA.
Dennis
Vida A
VA
Carter
Christina L
CL
Pillai
Shreekumar R
SR
Jefferson
Ayanna
A
Sahi
Shivendra V
SV
Moore
Eddie G
EG
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D015967:Gene Expression Regulation, Viral; D018928:Immunity, Mucosal; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology* / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D011994:Recombinant Proteins; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins