Safety and immunogenicity of S-Trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: a phase 1, randomised, double-blind, placebo-controlled trial

Richmond, Peter; Hatchuel, Lara; Dong, Min; Ma, Brenda; Hu, Branda; Smolenov, Igor; Li, Ping; Peng, Liang; Han, Htay Htay; Liang, Joshua G.; Clemens, Ralf

doi:10.1016/s0140-6736(21)00241-5

Cited by 247 publications

(282 citation statements)

References 26 publications

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“…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%

“…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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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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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“… ☑ Novavax, NVX-CoV2373 SARS-CoV-2 39 , 51 Keech, NVX-CoV2373 Recombinant protein Recombinant nanoparticle vaccine expressing full-length spike protein with or without the Matrix M1 Adjuvant. ☑ ☑ Inovio, INO-4800 SARS-CoV-2 40 Tebas, INO-4800 DNA plasmid DNA plasmid vaccine expressing optimised, synthetic full-length spike protein gene ☑ Clover/GSK, SCB-2019 SARS-CoV-2 41 Richmond, SCB-2019 Recombinant protein subunit Stabilised trimeric spike protein vaccine with AS03 or CpG 1018/Alum Adjuvant. ☑ MVA-MERS-S MERS-CoV 42 Koch, MERS MVA rMVA Modified Vaccina Ankara (Poxvirus) expressing full-length spike protein ☑ VRC-SRSDNA015–00-VP SARS-CoV-1 43 Martin, SARS DNA DNA plasmid DNA plasmid encoding codon-optimized spike protein gene ☑ Sinovac-Inactivated SARS-CoV-1 44 Lin, SARS inactivated Inactivated virus (Sino3 strain) β-propiolactone inactivated vaccine with aluminium hydroxide adjuvant.…”

Section: Resultsmentioning

confidence: 99%

“…Interstudy analysis of ELISA-IgG GMT was conducted across published human studies 14 – 20 , 23 – 25 , 28 – 30 , 32 , 34 , 36 – 41 , 45 . A number of conclusions can be drawn regarding overall titer and the dose-dependent and boost dependent nature of ELISA-IgG Ab responses (Fig.…”

Section: Resultsmentioning

confidence: 99%

Comparative systematic review and meta-analysis of reactogenicity, immunogenicity and efficacy of vaccines against SARS-CoV-2

et al. 2021

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As SARS-CoV-2 vaccines are deployed worldwide, a comparative evaluation is important to underpin decision-making. We here report a systematic literature review and meta-analysis of Phase I/II/III human trials and non-human primates (NHP) studies, comparing reactogenicity, immunogenicity and efficacy across different vaccine platforms for comparative evaluation (updated to March 22, 2021). Twenty-three NHP and 32 human studies are included. Vaccines result in mostly mild, self-limiting adverse events. Highest spike neutralizing antibody (nAb) responses are identified for the mRNA-1273-SARS-CoV and adjuvanted NVX-CoV2373-SARS-CoV-2 vaccines. ChAdOx-SARS-CoV-2 produces the highest T cell ELISpot responses. Pre-existing nAb against vaccine viral vector are identified following AdH-5-SARS-CoV-2 vaccination, halving immunogenicity. The mRNA vaccines depend on boosting to achieve optimal immunogenicity especially in the elderly. BNT162b2, and mRNA-1273 achieve >94%, rAd26/5 > 91% and ChAdOx-SARS-CoV-2 > 66.7% efficacy. Across different vaccine platforms there are trade-offs between antibody binding, functional nAb titers, T cell frequency, reactogenicity and efficacy. Emergence of variants makes rapid mass rollout of high efficacy vaccines essential to reduce any selective advantage.

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“…There was a trend towards increased local and systemic reactogenicity after the second dose, although almost all reported AEs were mild-to-moderate and transient in nature. Although only the 3.75 µg dose level of CoVLP was used in the Phase study, data from the Phase 1 trial that included groups given unadjuvanted CoVLP at three dose levels (3.75, 7.5 and 15µg/dose) showed that local and systemic reactogenicity was higher in adjuvanted groups as compared to non-adjuvanted groups, as would be expected from its use with other antigens 25,33,34 . As expected 26 and has been observed for mRNA, adenovirus vector, inactivated virus, and recombinant protein-based COVID-19 vaccines [35][36][37][38][39][40][41][42] reduced reactogenicity was observed in the older adults.…”

Section: Discussionmentioning

confidence: 99%

Phase 2 Randomized Trial of an AS03 Adjuvanted Plant-Based Virus-Like Particle Vaccine for Covid-19 in Healthy Adults, Older Adults and Adults with Comorbidities

Gobeil

Pillet

Séguin

et al. 2021

Preprint

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The rapid spread of SARS-CoV-2 globally continues to impact humanity on a global scale with rising morbidity and mortality. Despite the development of multiple effective vaccines, new vaccines continue to be required to supply ongoing demand. We report Day 42 interim safety and immunogenicity data from a Phase 2, randomized, placebo-controlled trial in Adults aged 18+ immunized with a virus-like particle vaccine candidate produced in plants displaying SARS-CoV-2 spike glycoprotein (CoVLP) adjuvanted with AS03 (NCT04636697). This report focuses on presenting safety, tolerability and immunogenicity, as measured by neutralizing antibody (NAb) and cell mediated immunity (IFN-γ and IL-4 ELISpot) responses, in Adults aged 18-64 (Adults) and Older Adults aged 65+ (Older Adults). CoVLP adjuvanted with AS03 was well-tolerated and adverse events (AE) were primarily mild or moderate and of transient duration. AEs in Older Adults were more limited than those observed in the Adult population. CoVLP with AS03 induced a significant humoral immune response in both age cohorts. CoVLP with AS03 induced a greater humoral response in Adults than Older Adults after a single dose but this effect was overcome with a second dose when both age cohorts responded with NAb titers that were ~10-fold higher than those in a panel of sera from patients recovering from COVID-19. A single dose of CoVLP with AS03 induced a significant IFN-γ response in both age cohorts; a second dose significantly boosted IFN-γ and IL-4 responses in both age cohorts. Adults generated a stronger IFN-γ and IL-4 cellular response than did Older Adults after one or two doses of AS03-adjuvanted CoVLP. Safety and immunogenicity from Adults with comorbidities as well as final safety and immunogenicity responses after 12 months will be reported upon availability.

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Safety and immunogenicity of S-Trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: a phase 1, randomised, double-blind, placebo-controlled trial

Cited by 247 publications

References 26 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

Comparative systematic review and meta-analysis of reactogenicity, immunogenicity and efficacy of vaccines against SARS-CoV-2

Phase 2 Randomized Trial of an AS03 Adjuvanted Plant-Based Virus-Like Particle Vaccine for Covid-19 in Healthy Adults, Older Adults and Adults with Comorbidities

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