Cationic-nanogel nasal vaccine containing the ectodomain of RSV-small hydrophobic protein induces protective immunity in rodents.
Shingo UmemotoRika Nakahashi-OuchidaYoshikazu YukiShiho KurokawaTomonori MachitaYohei UchidaHiromi MoriTomoyuki YamanoueTakehiko ShibataShin-Ichi SawadaKazuya IshigeTakashi HiranoKohtaro FujihashiKazunari AkiyoshiYosuke KurashimaDaisuke TokuharaPeter B ErnstMasashi SuzukiHiroshi KiyonoPublished in: NPJ vaccines (2023)
Respiratory syncytial virus (RSV) is a leading cause of upper and lower respiratory tract infection, especially in children and the elderly. Various vaccines containing the major transmembrane surface proteins of RSV (proteins F and G) have been tested; however, they have either afforded inadequate protection or are associated with the risk of vaccine-enhanced disease (VED). Recently, F protein-based maternal immunization and vaccines for elderly patients have shown promising results in phase III clinical trials, however, these vaccines have been administered by injection. Here, we examined the potential of using the ectodomain of small hydrophobic protein (SHe), also an RSV transmembrane surface protein, as a nasal vaccine antigen. A vaccine was formulated using our previously developed cationic cholesteryl-group-bearing pullulan nanogel as the delivery system, and SHe was linked in triplicate to pneumococcal surface protein A as a carrier protein. Nasal immunization of mice and cotton rats induced both SHe-specific serum IgG and mucosal IgA antibodies, preventing viral invasion in both the upper and lower respiratory tracts without inducing VED. Moreover, nasal immunization induced greater protective immunity against RSV in the upper respiratory tract than did systemic immunization, suggesting a critical role for mucosal RSV-specific IgA responses in viral elimination at the airway epithelium. Thus, our nasal vaccine induced effective protection against RSV infection in the airway mucosa and is therefore a promising vaccine candidate for further development.
Keyphrases
- respiratory tract
- respiratory syncytial virus
- clinical trial
- protein protein
- phase iii
- amino acid
- sars cov
- binding protein
- high glucose
- small molecule
- diabetic rats
- randomized controlled trial
- chronic rhinosinusitis
- open label
- oxidative stress
- insulin resistance
- body mass index
- risk assessment
- preterm birth
- middle aged
- weight gain
- human health
- birth weight