S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates

Liang, Joshua G.; Su, Danmei; Song, Tian-Zhang; Zeng, Yilan; Huang, Weijin; Wu, Jianqing; Xu, Rong; Luo, Peiwen; Yang, Xiaofang; Zhang, Xiaodong; Luo, Shuangru; Li, Ying; Li, Xinglin; Huang, Jiaju; Wang, Qiang; Huang, Xueqin; Xu, Qingsong; Luo, Moulun; Huang, Anliang; Luo, Dongxia; Zhao, Chenyan; Yang, Fan; Han, Jian; Zheng, Yong‐Tang; Peng, Liang

doi:10.1038/s41467-021-21634-1

Cited by 135 publications

(110 citation statements)

References 41 publications

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“…5A-D). The Th1-biased CMI induced by adjuvanted S-Trimer antigen is consistent with results from our previous studies ( 16 ).…”

Section: Resultssupporting

confidence: 92%

“…Encouragingly, the CMI induced by the S-Trimers in this study appeared to be Th1-biased in nature, which is consistent with our previous studies evaluating adjuvanted Prototype S-Trimer ( 16,17 ).…”

Section: Discussionsupporting

confidence: 92%

“…Covalently-trimerized S-protein antigens were produced based on the original SARS-CoV-2 strain (Prototype S-Trimer) and South African variant (B.1.351 S-Trimer) utilizing Trimer-Tag © technology ( 16 ). Prototype S-Trimer is based on the native spike ectodomain sequences of the original SARS-CoV-2 strain (Wuhan-Hu-1), whereas the modified B.1.351 S-Trimer contains 3 RBD mutations (K417N, E484K, N501Y) and the D614G mutations found in the B.1.351 variant strain, while the N-terminal domain (NTD) and S2 sequences are based on the original strain (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…These circumstances necessitate the rapid evaluation of booster dose strategies in order to enhance neutralizing antibody responses to VOCs and the development of second generation COVID-19 vaccines which may confer optimized broadly-protective, cross-neutralizing characteristics. In this study, we produced a modified B.1.351 Spike -Trimer antigen (dubbed “B.1.351 S-Trimer”) and compared it with our Prototype S-Trimer ( 16,17 ) in a mouse immunogenicity study. Heterologous prime-boost and bivalent vaccine approaches were also evaluated, as well as the effect of a third dose (booster dose).…”

Section: Introductionmentioning

confidence: 99%

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Broad neutralization against SARS-CoV-2 variants induced by a modified B.1.351 protein-based COVID-19 vaccine candidate

et al. 2021

Preprint

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Beginning in late 2020, the emergence and spread of multiple variant SARS-CoV-2 strains harboring mutations which may enable immune escape necessitates the rapid evaluation of second generation COVID-19 vaccines, with the goal of inducing optimized immune responses that are broadly protective. Here we demonstrate in a mouse immunogenicity study that two doses of a modified B.1.351 spike (S)-Trimer vaccine (B.1.351 S-Trimer) candidate can induce strong humoral immune responses that can broadly neutralize both the original SARS-CoV-2 strain (Wuhan-Hu-1) and Variants of Concern (VOCs), including the UK variant (B.1.1.7), South African variant (B.1.351) and Brazil variant (P.1). Furthermore, while immunization with two doses (prime-boost) of Prototype S-Trimer vaccine (based on the original SARS-CoV-2 strain) induced lower levels of cross-reactive neutralization against the B.1.351 variant, a third dose (booster) administered with either Prototype S-Trimer or B.1.351 S-Trimer was able to increase neutralizing antibody titers against B.1.351 to levels comparable to neutralizing antibody titers against the original strain elicited by two doses of Prototype S-Trimer.

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“…5A-D). The Th1-biased CMI induced by adjuvanted S-Trimer antigen is consistent with results from our previous studies ( 16 ).…”

Section: Resultssupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Broad neutralization against SARS-CoV-2 variants induced by a modified B.1.351 protein-based COVID-19 vaccine candidate

et al. 2021

Preprint

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“…Clover's vaccine SCB-2019 is also a Strimer vaccine. Different with NVX-Cov2373, the preparation of SCB-2019 relies on antigen fused in-frame to Trimer-Tag and subsequent self-trimerization of Trimer-Tag (47). While ZF2001, another leading protein vaccine, comprises a homogeneous RBD-dimers as a tandem-repeat single chain (40).…”

Section: Recombinant Protein Vaccinementioning

confidence: 99%

COVID-19 Vaccines: Current Understanding on Immunogenicity, Safety, and Further Considerations

Mao

Zhang

et al. 2021

Front. Immunol.

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The world has entered the second wave of the COVID-19 pandemic, and its intensity is significantly higher than that of the first wave of early 2020. Many countries or regions have been forced to start the second round of lockdowns. To respond rapidly to this global pandemic, dozens of COVID-19 vaccine candidates have been developed and many are undergoing clinical testing. Evaluating and defining effective vaccine candidates for human use is crucial for prioritizing vaccination programs against COVID-19. In this review, we have summarized and analyzed the efficacy, immunogenicity and safety data from clinical reports on different COVID-19 vaccines. We discuss the various guidelines laid out for the development of vaccines and the importance of biological standards for comparing the performance of vaccines. Lastly, we highlight the key remaining challenges, possible strategies for addressing them and the expected improvements in the next generation of COVID-19 vaccines.

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

Deng

Sun

et al. 2022

Advanced Materials

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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.

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S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates

Cited by 135 publications

References 41 publications

Broad neutralization against SARS-CoV-2 variants induced by a modified B.1.351 protein-based COVID-19 vaccine candidate

Broad neutralization against SARS-CoV-2 variants induced by a modified B.1.351 protein-based COVID-19 vaccine candidate

COVID-19 Vaccines: Current Understanding on Immunogenicity, Safety, and Further Considerations

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

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