A nanogel-based trivalent PspA nasal vaccine protects macaques from intratracheal challenge with pneumococci

Current polysaccharide-based pneumococcal vaccines are effective but not compatible with all serotypes of Streptococcus pneumoniae. We previously developed an adjuvant-free cationic nanogel nasal vaccine containing pneumococcal surface protein A (PspA), which is expressed on the surfaces of all pneumococ-cal serotypes. Here, to address the sequence diversity of PspA proteins, we formulated a cationic nanogel-based trivalent pneumococcal nasal vaccine and demonstrated the vaccine's immunogenicity and protec-tive efficacy in macaques by using a newly developed nasal spray device applicable to humans. Nasal vac-cination of macaques with cationic cholesteryl pullulan nanogel (cCHP)-trivalent PspA vaccine effectively induced PspA-specific IgGs that bound to pneumococcal surfaces and triggered complement C3 deposi-tion. The immunized macaques were protected from pneumococcal intratracheal challenge through both inhibition of lung inflammation and a dramatic reduction in the numbers of bacteria in the lungs. These results demonstrated that the cCHP-trivalent PspA vaccine is an effective candidate vaccine against pneu-mococcal infections. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

A polysaccharide-based pneumococcal vaccine has been developed to effectively inhibit various serotypes of Streptococcus pneumoniae infections, demonstrating good immunogenicity and protective efficacy in macaques. The vaccine induces PspA-specific IgGs, triggers complement C3 deposition, and enhances resistance to pneumococcal infections by inhibiting lung inflammation and reducing bacterial numbers in the lungs.