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

2021; Elsevier BV; Volume: 39; Issue: 25 Linguagem: Inglês

10.1016/j.vaccine.2021.04.069

1873-2518

Rika Nakahashi-Ouchida, Yohei Uchida, Yoshikazu Yuki, Yuko Katakai, Tomoyuki Yamanoue, Hiromi Ogawa, Yoshiko Munesue, Nozomi Nakano, Kouji Hanari, Takashi Miyazaki, Yuki Saito, Shingo Umemoto, Shin‐ichi Sawada, Reshmi Mukerji, David E. Briles, Yasuhiro Yasutomi, Kazunari Akiyoshi, Hiroshi Kiyono,

Respiratory viral infections research

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 pneumococcal 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 protective efficacy in macaques by using a newly developed nasal spray device applicable to humans. Nasal vaccination 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 deposition. 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 pneumococcal infections.