Abstract
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.
Keywords: S. pneumoniae serotype type 14; SARS-CoV-2; capsular polysaccharide; chemical conjugation; nanoparticle vaccines; receptor binding domain.
【저자키워드】 SARS-CoV-2, Receptor binding domain, S. pneumoniae serotype type 14, capsular polysaccharide, chemical conjugation, nanoparticle vaccines, 【초록키워드】 COVID-19, Vaccine, vaccination, Infectious diseases, Diseases, Mortality, Cellular immune response, COVID-19 pandemic, variant, SARS-CoV-2 variant, Infection, omicron, immunization, Spike protein, Receptor binding domain, serum, clinical evaluation, mice, RBD, immune responses, SARS-CoV-2 spike protein, VOCs, death, vaccine platform, polysaccharide, thermal stability, capsular polysaccharide, rhesus macaques, cross-neutralize, S. pneumoniae, Streptococcus pneumoniae, humoral, T helper cell, other infectious diseases, helper cell, Support, serotype, RATs, domain, mouse-adapted strain, Final, murine models, potency, cellular immune responses, backbone, Prevent, caused, induce, Type, exhibit, highlighting, capsular, the SARS-CoV-2, 【제목키워드】 nanoparticle, development, Against,