A nanogel-based trivalent PspA nasal vaccine protects macaques from intratracheal challenge with pneumococci. Issue 25 (8th June 2021)

• Record Type: Journal Article
• Authors: Nakahashi-Ouchida, Rika; Uchida, Yohei; Yuki, Yoshikazu; Katakai, Yuko; Yamanoue, Tomoyuki; Ogawa, Hiromi; Munesue, Yoshiko; Nakano, Nozomi; Hanari, Kouji; Miyazaki, Takashi; Saito, Yuki; Umemoto, Shingo; Sawada, Shin-ichi; Mukerji, Reshmi; Briles, David E.; Yasutomi, Yasuhiro; Akiyoshi, Kazunari; Kiyono, Hiroshi
• Is Part Of: Vaccine. Volume 39:Issue 25(2021)
• Page Start: 3353
• Page End: 3364
• Publication Date: 2021-06-08
• Subjects: Pneumonia -- Cationic nanogel -- Nasal vaccine -- PspA -- Non-human primate; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2021.04.069
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: cCHP nanogel trivalent PspA vaccine effectively induces PspA-specific IgG in macaque. PspA-specific IgG bound to the pneumococcal surface and triggered C3 deposition. Vaccinated macaques were protected from pneumococcal intratracheal challenge. A nasal spray-application device was developed for the cCHP nanogel nasal vaccine. The vaccine might provide broad protection against pneumococcal infections in humans. Abstract: 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.