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  • Rational Development of a P...
    Deng, Yongqiang; Li, Jing; Sun, Chunyun; Chi, Hang; Luo, Dan; Wang, Rui; Qiu, Hongying; Zhang, Yanjing; Wu, Mei; Zhang, Xiao; Huang, Xun; Xie, Liangzhi; Qin, Chengfeng

    Advanced materials (Weinheim), 05/2022, Letnik: 34, Številka: 21
    Journal Article

    The ongoing COVID‐19 pandemic caused by SARS‐CoV‐2 has led to millions of deaths worldwide. Streptococcus pneumoniae (S. pneumoniae) remains a major cause of mortality in underdeveloped countries. A vaccine that prevents both SARS‐CoV‐2 and S. pneumoniae infection represents a long‐sought “magic bullet”. Herein, a nanoparticle vaccine, termed SCTV01B, is rationally developed by using the capsular polysaccharide of S. pneumoniae serotype 14 (PPS14) as the backbone to conjugate with the recombinant receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein. The final formulation of conjugated nanoparticles in the network structure exhibits high thermal stability. Immunization with SCTV01B induces potent humoral and Type 1/Type 2 T helper cell (Th1/Th2) cellular immune responses in mice, rats, and rhesus macaques. In particular, SCTV01B‐immunized serum not only broadly cross‐neutralizes all SARS‐CoV‐2 variants of concern (VOCs), including the most recent Omicron variant, but also shows high opsonophagocytic activity (OPA) against S. pneumoniae serotype 14. Finally, SCTV01B vaccination confers protection against challenges with the SARS‐CoV‐2 mouse‐adapted strain and the original strain in established murine models. Collectively, these promising preclinical results support further clinical evaluation of SCTV01B, highlighting the potency of polysaccharide‐RBD‐conjugated nanoparticle vaccine platforms for the development of vaccines for COVID‐19 and other infectious diseases. A bivalent nanoparticle vaccine is rationally developed by conjugating capsular polysaccharide of Streptococcus pneumoniae serotype 14 with the receptor‐binding domain (RBD) of SARS‐CoV‐2 spike protein. Immunization with this vaccine induces potent protective immune responses against both SARS‐CoV‐2 variants and S. pneumoniae. This universal polysaccharide–protein‐conjugated vaccine platform provides a new tool to fight against cocirculating viral and bacterial pathogens.