Improvement of a SARS-CoV-2 vaccine by enhancing the conjugation efficiency of the immunogen to self-assembled nanoparticles

Zhang, Xiantao; Yuan, Yuhong; Wu, Bolin; Wang, Xuemei; Lin, Yingtong; Luo, Yong; Li, Rong; Chen, Tao; Deng, Jieyi; Xu, Zhouyi; Zou, Fan; He, Xin; Zhang, Hui

doi:10.1038/s41423-021-00736-2

Cited by 13 publications

(19 citation statements)

References 8 publications

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“…To increase conjugation efficiency, we recently developed a GvTagOpti/ SdCatcher (Gv/Sd) system derived from Gardnerella vaginalis and Streptococcus dysgalactiae, respectively. This conjugation system presents immunogen on nanoparticles with much higher efficiency (Zhang et al, 2021c). The Sd-coding sequence was genetically fused at the N terminus of ferritin (Sd-ferritin), whereas the Gv-coding sequence was fused at the N-terminus of the D614G_RBD or B.1.351_RBD sequence (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, we optimized the conjugation efficiency by generating several mutants based upon the structural prediction. Finally, we identified a potent combination of GvTagOpti (Gv) and SdCatcher (Sd) from Gardnerella vaginalis and Streptococcus dysgalactiae respectively, which significantly enhanced the assemble efficiency and the production of the SARS-CoV-2 NP vaccine (Zhang et al, 2021c). The Sd-Ferritin was expressed and purified from Escherichia coli (E.coli).…”

Section: Methods Details Protein Expression and Purificationmentioning

confidence: 99%

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A bivalent nanoparticle vaccine exhibits potent cross-protection against the variants of SARS-CoV-2

et al. 2022

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The inoculation of vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is undergoing worldwide. However, the emergence of SARS-CoV-2 variants could confer immune evasion. Here we develop a bivalent nanoparticle vaccine, which displays the RBDs of both D614G and B.1.351 strains. With a prime-boost or a single-dose strategy, this vaccine elicits a robust neutralizing antibody and full protection against the infection of authentic D614G or B.1.351 strains in the human angiotensin-converting enzyme 2 transgene mice. Interestingly, after 8 months since the D614G-specific vaccine inoculated, a new boost with this bivalent vaccine potently elicits cross-neutralizing antibodies for SARS-CoV-2 variants in rhesus macaques. We suggest that the D614G/B.1.351-bivalent vaccine could be used as an initial single-dose or a sequential enforcement-dose to prevent SARS-CoV-2 and its variants.

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Section: Resultsmentioning

confidence: 99%

Section: Methods Details Protein Expression and Purificationmentioning

confidence: 99%

A bivalent nanoparticle vaccine exhibits potent cross-protection against the variants of SARS-CoV-2

et al. 2022

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“…To connect RBD immunogen and self‐assembled ferritin particles, we adapted a GvTagOpti/SdCatcher (GV/SD) system which derived from Gardnerella Vaginalis and Streptococcus Dysgalactiae respectively and developed by us. [ 21 ] The Sd‐coding sequence was genetically fused to the N‐terminus of ferritin (Sd‐Ferritin), while the Gv‐coding sequence was fused at the N‐terminus of B.1.617.2_RBD, D614G_RBD, and the B.1.351_RBD sequence. The purified Gv‐B.1.617.2_RBD, Gv‐D614G_RBD, and Gv‐B.1.351_RBD were irreversibly and covalently conjugated to Sd‐Ferritin to generate B.1.617.2_RBD‐NP, D614G_RBD‐NP and B.1.351_RBD‐NP, followed by purification by gel filtration (Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

“…Sd‐Ferritin was expressed and purified from E. coli. [ 21 ] Briefly, the Sd gene was fused to the N‐terminus of the Ferritin gene, and the DNA sequence of Sd‐Ferritin was cloned into the pET28a vector. The constructed plasmid was transformed into BL21 (Takara) prokaryotic expression bacteria.…”

Section: Methodsmentioning

confidence: 99%

Development of Receptor Binding Domain (RBD)‐Conjugated Nanoparticle Vaccines with Broad Neutralization against SARS‐CoV‐2 Delta and Other Variants

et al. 2022

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The SARS-CoV-2 Delta (B.1.617.2) strain is a variant of concern (VOC) that has become the dominant strain worldwide in 2021. Its transmission capacity is approximately twice that of the original strain, with a shorter incubation period and higher viral load during infection. Importantly, the breakthrough infections of the Delta variant have continued to emerge in the first-generation vaccine recipients. There is thus an urgent need to develop a novel vaccine with SARS-CoV-2 variants as the major target. Here, receptor binding domain (RBD)-conjugated nanoparticle vaccines targeting the Delta variant, as well as the early and Beta/Gamma strains, are developed. Under both a single-dose and a prime-boost strategy, these RBD-conjugated nanoparticle vaccines induce the abundant neutralizing antibodies (NAbs) and significantly protect hACE2 mice from infection by the authentic SARS-CoV-2 Delta strain, as well as the early and Beta strains. Furthermore, the elicitation of the robust production of broader cross-protective NAbs against almost all the notable SARS-CoV-2 variants including the Omicron variant in rhesus macaques by the third re-boost with trivalent vaccines is found. These results suggest that RBD-based monovalent or multivalent nanoparticle vaccines provide a promising second-generation vaccine strategy for SARS-CoV-2 variants.

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“…Another COVID-19 vaccine consisting of ferritin-nanoparticle-RBD and CpG-1826 was reported, which elicited potent and long-lasting memory antibody response. 508 Polymer nanoparticle adjuvants. Recently, Roy and colleagues used PLGA-PEI polymer nanoparticles to co-deliver the RIG-I agonist (PUUC) and different TLR agonists (MPLA, R848 or CpG) together with SARS-CoV-2 spike protein.…”

Section: Nanotechnology Adjuvants In Preclinical Vaccines Against Inf...mentioning

confidence: 99%

Adjuvant physiochemistry and advanced nanotechnology for vaccine development

et al. 2023

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Improvement of a SARS-CoV-2 vaccine by enhancing the conjugation efficiency of the immunogen to self-assembled nanoparticles

Cited by 13 publications

References 8 publications

A bivalent nanoparticle vaccine exhibits potent cross-protection against the variants of SARS-CoV-2

A bivalent nanoparticle vaccine exhibits potent cross-protection against the variants of SARS-CoV-2

Development of Receptor Binding Domain (RBD)‐Conjugated Nanoparticle Vaccines with Broad Neutralization against SARS‐CoV‐2 Delta and Other Variants

Adjuvant physiochemistry and advanced nanotechnology for vaccine development

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