Rational Development of a Polysaccharide–Protein‐Conjugated Nanoparticle Vaccine Against SARS‐CoV‐2 Variants and Streptococcus pneumoniae

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.

A Polysaccharide-RBD-Fc-Conjugated COVID-19 Vaccine, SCTV01A, Showed High Immunogenicity and Low Toxicity in Animal Models

“…S. pneumoniae isolate CMCC 31614 (serotype 14) was obtained from the National Center for Medical Culture Collections (CMCC, China). S. pneumoniae were cultured and lysed, and pneumococcal capsular polysaccharides were prepared as previously described [ 28 ].…”

“…Pseudoviruses used in neutralization assays were constructed as described previously [ 28 ]. Pseudoviruses of Wuhan-Hu-1, Delta, BA.1, and BA.4/BA.5 were constructed based on GISAID accession ID EPI_ISL_402125, EPI_ISL_1999775, EPI_ISL_6640917, and EPI_ISL_11542270.1, respectively.…”

“…Among these S. pneumoniae pneumococcal polysaccharides (PPS), PPS from S. pneumoniae serotype 14 (PPS14) showed a superior binding capacity to CLRs on DCs [ 24 , 25 , 26 ] and can be efficiently internalized by DCs [ 27 ]. The contribution of PPS14 to enhance the immunogenicity of RBD has been verified in our previously developed nanoparticle vaccine which chemically conjugates recombinant SARS-CoV-2 RBD and PPS14 [ 28 ].…”

Insights for COVID-19 in 2023

“…Nor would it be recommended to combine them in young people, especially males under 40 years of age, in whom adverse effects may be more frequent [ 45 ] and the risk of both diseases is low. In future campaigns it is likely that vaccines will be available to protect against both viruses in a single dose [ 46 - 48 ] and even against SARS-CoV2 and pneumococcus [ 49 ], but its efficacy and safety have yet to be demonstrated in humans.…”

Effect and mechanism of paclitaxel loaded on magnetic Fe 3 O 4 @mSiO 2 -NH 2 -FA nanocomposites to MCF-7 cells

“…Polysaccharide, a biopolymer, is used to modify the surface of the nanoparticles by embedding covalent coupling. Hence, a hydrophilic coating can improve the biocompatibility and stability of nanoparticles (Deng et al., 2022 ). Polysaccharides are classified as neutral, positively charged, or negatively charged owing to their surface charge properties.…”