Synthetic LbL nanoparticle vaccines containing the chemokine mimic epitope of RSV-G protein and a CD8 epitope of RSV-M2 protein elicit broad-based cellular and humoral responses (155.7)

Nanoparticle vaccines synthesized via layer-by-layer (LbL) fabrication were loaded with designed peptides representing epitopes of the attachment (G) and matrix (M2) proteins of respiratory syncytial virus. The CX3C chemokine mimic epitope of RSV-G has been proposed to contribute to inflammatory responses post-challenge while CD8+ T-cell responses against RSV M2 have been shown to limit the severity of infection and inflammatory pathology. Both monovalent designs (G or M2) and multivalent designs (G+M2) were tested. Mice immunized with RSV-G nanoparticles produced antibody responses that recognized the CX3C epitope only in its folded conformation and not in a linearized state. The same sera also bound native RSV-G protein, inhibited binding of RSV-G protein to the CX3CR1 chemokine receptor, and inhibited migration of human leukocytes toward RSV-G protein. Mice immunized with RSV M2 nanoparticles generated CD8+ T-cell responses and in vitro CTL activity against M2-labeled target cells. The multivalent vaccines containing both G and M2 elicited higher antibody responses to RSV-G and, surprisingly, more potent cellular responses against RSV-M2. These novel nanoparticle vaccines are currently being tested for the induction of neutralizing antibody responses and protection from viral challenge. If successful, the LbL nanoparticle fabrication strategy will provide an innovative approach to formulating safe and effective subunit vaccines for respiratory pathogens including RSV.