RSV pre-fusion F protein enhances the G protein antibody and anti-infectious responses

Respiratory syncytial virus (RSV) infection in children is the most common viral respiratory infection and can cause severe lung damage or death. There is no licensed vaccine for preventing RSV infection. Previously we demonstrated that an RSV vaccine, BARS13, consisting of recombinant G protein from E. coli plus cyclosporine A (CsA) as an immune-modulator, can protect animals from RSV challenge without inducing vaccine-enhanced disease (VED). To maximize the efficacy of such a vaccine, we introduced RSV pre-fusion F protein (pre-F) to form a new vaccine comprised of the pre-F and G proteins with the CsA. Two intramuscular immunizations with the vaccine induced a higher level of neutralizing antibodies against RSV and protected mice from RSV challenge without incurring VED. Interestingly, the addition of the pre-F to the vaccine facilitated anti-G antibody production and protection from RSV infection mainly via induction of antibodies against the central conserved domain (CCD) of the G protein which correlated with blocking the CX3C-CX3CR1 interaction. A 15 amino acid sequence (FP4) within the F2 region of pre-F served as a CD4(+) Th epitope to facilitate the anti-G antibody response. Collectively, such a combination of the FP4 peptide with the G protein and CsA provides a novel strategy for developing a safe and maximally effective recombinant G protein-containing RSV vaccine.