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Clover SCB-2019 COVID-19 Vaccine

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October 7, 2021
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Clover SCB-2019 COVID-19 Vaccine Description

Clover Biopharmaceutical COVID-19 vaccine (SCB-2019, CpG 1018/Alum) is a trimeric SARS-CoV-2 spike (S)-protein subunit vaccine candidate developed by Clover when combining the trimeric SARS-CoV-2 spike (S)-protein with the company's proprietary Trimer-Tag© technology.

The COVID-19 S-Trimer vaccine SCB-2019 (CpG 1018/Alum) resembles the native trimeric viral spike protein produced via a rapid mammalian cell-culture-based expression system.

Dynavax developed CpG 1018 adjuvant to provide an increased vaccine immune response, as demonstrated in HEPLISAV-B. In addition, CpG 1018 adjuvant provides a well-developed technology and a significant safety database, potentially accelerating the development and large-scale manufacturing of a COVID-19 vaccine.

Trimer-Tag is an innovative drug development platform that allows the production of novel, covalently-trimerized fusion proteins. Many major disease targets are trimerization-dependent such as the tumor necrosis factor superfamily (involved in extrinsic apoptosis, immune co-stimulation, and inflammation) as well as enveloped RNA virus antigens responsible for entry into host cells. Thus, Trimer-Tag may be an important platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses, stated an article published by the journal Nature in March 2021.

In Phase 1 clinical trial, Clover's COVID-19 vaccine-induced levels of neutralizing antibodies were higher than in people previously infected with SARS-CoV-2. In addition, strong Th1-biased cell-mediated immune responses were observed.

Clover announced on September 22, 2021, that Clover's adjuvanted protein-based COVID-19 vaccine candidate, SCB-2019 achieved the primary efficacy endpoint and secondary efficacy endpoints in SPECTRA, a global pivotal Phase 2/3 clinical trial. Vaccine efficacy was successfully demonstrated in an environment where 100% of SARS-CoV-2 strains observed in the efficacy analysis were variants. And SCB-2019 demonstrated 79% overall efficacy against COVID-19 of any severity caused by the globally dominant Delta variant, which currently comprises over 90% of all cases worldwide. Efficacy was 92% against the Gamma variant and 59% against the Mu variant, and collectively these three strains (Delta, Gamma, and Mu) comprised 73% of all strains identified in the study. Overall efficacy was 67% against COVID-19 of any severity caused by any strain in the study, successfully meeting the primary endpoint of the trial.

Data from the SPECTRA final analysis have been made available in a presentation that can be found on Clover's corporate website.

Clover plans to submit conditional regulatory approval applications to the EMA, the NMPA, and the WHO in the second half of 2021 and plans to commence product launch by the end of 2021.

SCB-2019 - DrugBank Accession Number: DB15805

Clover SCB-2019 COVID-19 Vaccine History

Preclinical data have shown Clover's protein-based adjuvanted COVID-19 vaccine candidate, S-Trimer, induces a strong neutralizing immune response in animals and protects nonhuman primates from a SARS-CoV-2 challenge. And strong immune response and protection were observed with adjuvant systems from GSK and Dynavax. These positive preclinical data supported the decision to progress adjuvanted vaccine candidates using both adjuvants into Clover's ongoing Phase 1 clinical study of S-Trimer in healthy adult and elderly participants, said the company on September 25, 2020.

On November 3, 2020, CEPI extended its partnership with Clover Biopharmaceuticals to fund the COVID-19 vaccine candidate through global Phase 2/3 study to licensure. As a result, CEPI's total investment in Clover's S-Trimer vaccine candidate will be up to $328 million, including previously announced commitments of $69.5 million, which have funded preclinical studies and Phase 1 clinical trials.

On December 4, 2020, Clover announced the Phase 1 trial was a randomized, observer-blind, placebo-controlled study to assess the safety, reactogenicity, and immunogenicity of the adjuvanted COVID-19 S-Trimer vaccine candidates formulated with different antigen levels. No serious adverse events related to the vaccine candidates studied were reported. The majority of adverse events were mild and transient. S-Trimer is adjuvanted with GSK's pandemic adjuvant system-induced neutralizing antibody titers (seroconversion) in 100% of participants at the selected 9 µg S-Trimer dose in both adult and elderly groups, with geometric mean titers (GMT) greater than 1:1,800. In addition, CpG-1018/alum-adjuvanted S-Trimer induced neutralizing antibodies in 100% of adult participants at the selected 30 µg S-Trimer dose with GMT greater than 1:1,000 seroconversion was observed in 88% (7 out of 8) in the elderly. Strong Th1 cell-mediated immune responses were also observed for the vaccine candidates with either adjuvant.

The new CEPI funding announced on November 4, 2020, will also enable additional clinical studies in special populations, such as people with autoimmune conditions, immunocompromised individuals, pregnant women, and children. In parallel to the clinical development process, the program will continue scaling up the manufacturing process to potentially enable the production of more than one billion vaccine doses annually and build up vaccine inventory, which – if the vaccine is proven to be safe and effective - could be deployed rapidly upon licensure. CEPI published 'From lab to potential jab: Clover's COVID-19 vaccine story' on July 1, 2021.

On September 22, 2021, Clover Biopharmaceuticals, Ltd. and CEPI announced that Clover's adjuvanted protein-based COVID-19 vaccine candidate, SCB-2019 (CpG 1018/Alum) achieved the primary efficacy endpoint and secondary efficacy endpoints in SPECTRA, a global pivotal Phase 2/3 clinical trial. Vaccine efficacy was successfully demonstrated in an environment where 100% of SARS-CoV-2 strains observed in the efficacy analysis were variants. SCB-2019 (CpG 1018/Alum) demonstrated 79% overall efficacy against COVID-19 of any severity caused by the globally dominant Delta variant. Overall efficacy was 67% against COVID-19 of any severity caused by any strain in the study, successfully meeting the primary endpoint of the trial. Clover's vaccine candidate is one of the first to demonstrate significant efficacy against Delta in a double-blind, randomized clinical trial. 

Joshua Liang is the co-inventor of the COVID-19 S-Trimer vaccine. Clover Biopharmaceuticals is a global clinical-stage biotechnology company based in Chengdu, China, focused on discovering and developing transformative biologic therapies and vaccines.

Clover SCB-2019 COVID-19 Vaccine Indication

COVID-19 S-Trimer (SCB-2019) is indicated to prevent SARS-CoV-2 infection, which causes COVID-19 disease. The adolescent (ages 12-18) subgroup in the SPECTRA clinical trial has also initiated enrollment and will complete enrollment in 2021.

Clover SCB-2019 COVID-19 Vaccine Storage Requirements

Preliminary results from stability studies have demonstrated that S-Trimer is stable at 2-8o C for at least 6-months (longer-term stability studies are ongoing) and stable at room temperature and 40o C for at least one month, in line with the adjuvants tested. Thus, Clover's COVID-19 vaccine candidates' ability to be stored in standard refrigeration temperatures makes them suitable for broad global distribution based on current results.

Clover SCB-2019 COVID-19 Vaccine News

September 28, 2021 - Science.org published: New Chinese vaccine could bolster global arsenal. Protein-based shots developed by Clover are shown to protect against five variants.

September 22, 2021 - Clover's COVID-19 Vaccine Candidate Demonstrates 79% Efficacy Against Delta in Global Phase 2/3 SPECTRA Trial Dominated by Variants of Concern and Interest. And, the first COVID-19 vaccine to demonstrate significantly reduced risk of COVID-19 disease in previously infected individuals. Dr. Richard Hatchett, CEO of CEPI added, "... this vaccine is poised to play a significant role in protecting those most at risk from COVID-19, wherever they are in the world." 

September 22, 2021 - Dynavax Technologies Corporation (Nasdaq: DVAX) announced that Clover Biopharmaceuticals reported positive data for their protein-based COVID-19 vaccine candidate, SCB-2019 (CpG 1018/Alum) adjuvanted with Dynavax's CpG 1018 adjuvant, which achieved the primary and secondary efficacy endpoints in SPECTRA, a global pivotal Phase 2/3 clinical trial that enrolled over 30,000 participants. Vaccine efficacy was successfully demonstrated in an environment where 100% of SARS-CoV-2 strains observed in the efficacy analysis were variants.

September 9, 2021 - Clover Biopharmaceuticals, Ltd. announced Zhejiang Clover Biopharmaceutical, Inc., received a Pharmaceutical Manufacturing Permit from the Zhejiang Medical Products Administration to produce Clover's protein-based COVID-19 vaccine candidate at its facility in Changxing, Zhejiang province, China.

July 6, 2021 - Clover announced the completion of targeted enrollment of adult and elderly participants in SPECTRA, a global pivotal Phase 2/3 clinical trial evaluating the efficacy, safety, and immunogenicity of SCB-2019 (CpG 1018/Alum), Clover's COVID-19 vaccine candidate. The adolescent (ages 12-18) subgroup in SPECTRA has also initiated enrollment and will complete enrollment in Q3 2021.

July 1, 2021 - This blog takes a closer look at CEPI's collaboration with Clover, some of the additional CEPI programs it leverages, and the potential advantages of Clover's innovative vaccine technology, which could strengthen global efforts to end the acute phase of this devastating pandemic.

June 30, 2021 - Clover Biopharmaceuticals announced an advance purchase agreement with Gavi, the Vaccine Alliance, to provide up to 414 million doses of its protein-based COVID-19 vaccine candidate for procurement through the COVAX Facility. Gavi CEO Seth Berkley: "The pandemic continues to evolve, and in order to be best prepared, COVAX's actively managed, diverse portfolio will be critical to meeting countries' needs and protecting against risks such as regulatory delays, variants, and supply constraints. Today's agreement with Clover Biopharmaceuticals is yet another important step in that direction."

June 30, 2021 - Clover Biopharmaceuticals and Dynavax Technologies Corporation announced the execution of a commercial supply agreement of Dynavax's CpG 1018TM advanced adjuvant for use in Clover's protein-based COVID-19 vaccine candidate, SCB-2019 (CpG 1018/Alum). The commercial supply agreement extends to the end of 2022. The agreement includes doses for delivery in 2021, manufactured under the previously announced funding agreement between Coalition for Epidemic Preparedness Innovations and Dynavax.

March 24, 2021 - Clover Biopharmaceuticals and Dynavax Technologies Corporation announced the first participants had been dosed in Clover's SPECTRA trial (Study Evaluating Protective-Efficacy and Safety of Clover's Trimeric Recombinant Protein-based and Adjuvanted COVID-19 Vaccine), a global Phase 2/3 clinical trial evaluating the efficacy, safety, and immunogenicity of Clover's protein-based S-Trimer COVID-19 vaccine candidate adjuvanted with Dynavax's CpG 1018 plus alum.

March 1, 2021 - Nature study: S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates. Our data demonstrate that S-Trimer adjuvanted with either AS03 or CpG 1018 plus alum can induce robust humoral and cellular immune responses in various animal species and protect against SARS-CoV-2 infection in nonhuman primates, with no signs of disease enhancement. Collectively, these results support the advancement of adjuvanted S-Trimer through human clinical studies to further demonstrate safety, immunogenicity, and vaccine efficacy. 

February 23, 2021 - Clover Biopharmaceuticals announced the completion of an oversubscribed $230 million Series C financing. This financing round brings Clover's total capital raised in the last 12 months to over $400 million. The proceeds will support the continued development and expansion of Clover's pipeline of protein-based vaccines and biologic cancer therapies utilizing its innovative and proprietary Trimer-Tag© technology platform. Clover expects to initiate a global Phase 2/3 efficacy trial for SCB-2019 (S-Trimer), its COVID-19 vaccine candidate, in the first half of 2021 and has initiated production planning for potentially hundreds of millions of vaccine doses in 2021.

February 8, 2021 - The Lancet Study: S-Trimer (SCB-2019) Protein Subunit Vaccine for COVID-19. The SCB-2019 vaccine formulated with AS03 or CpG/Alum adjuvants was well tolerated and elicited robust humoral and cellular immune responses against SARS-CoV-2.

February 1, 2021 - Clover Biopharmaceuticals Announces Publication of Phase 1 Clinical Trial Data for its Adjuvanted COVID-19 Vaccine Candidates in The Lancet. Clover plans to initiate a global Phase 2/3 study to evaluate the S-Trimer COVID-19 vaccine candidate's safety and efficacy adjuvanted with Dynavax's advanced adjuvant CpG 1018 plus alum within the next few months. The Coalition for Epidemic Preparedness Innovations (CEPI) has committed to funding Clover's S-Trimer COVID-19 vaccine candidate through licensure with a total investment of up to$328 million, a portion of which will support the global Phase 2/3 study.

January 29, 2021 - The Lancet study: Safety and immunogenicity of S-Trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: a phase 1, randomized, double-blind, placebo-controlled trial. The SCB-2019 vaccine, comprising S-Trimer protein formulated with either AS03 or CpG/Alum adjuvants, elicited robust humoral and cellular immune responses against SARS-CoV-2, with high viral neutralizing activity. In addition, both adjuvanted vaccine formulations were well-tolerated and are suitable for further clinical development.

December 4, 2020 - Clover Biopharmaceuticals announced positive clinical data from its Phase 1 trial demonstrating that its protein-based COVID-19 S-Trimer vaccine candidates in combination with adjuvants from either GSK or Dynavax induce strong immune responses, including neutralizing antibodies and cell-mediated immunity, as well as favorable safety and tolerability profiles in 150 adult and elderly participants.

November 3, 2020 - The Coalition for Epidemic Preparedness Innovations announced that it would fund the development of the protein-based S-Trimer COVID-19 vaccine candidate by China-based Sichuan Clover Biopharmaceuticals, Inc. through a global pivotal Phase 2/3 efficacy clinical trial and to licensure in China and globally if the vaccine is proven to be safe and effective.

September 25, 2020 - Clover Biopharmaceuticals Announces Positive Preclinical Data and Updates on Phase 1 Study for its Adjuvanted S-Trimer COVID-19 Vaccine Candidate.

September 24, 2020 - Study: S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates. 'Trimer-Tag may be an important new platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.'

July 8, 2020 - The Coalition for Epidemic Preparedness Innovations announced the expansion of its partnership with Sichuan Clover Biopharmaceuticals, Inc. to rapidly advance Clover's development and manufacture protein-based COVID-19 S-Trimer vaccine candidate, which is based on Clover's proprietary Trimer-Tag© vaccine technology platform.

June 19, 2020 - Clover Biopharmaceuticals announced that the first participants had been dosed in Phase 1 first-in-human study evaluating the company's COVID-19 S-Trimer subunit vaccine candidate (SCB-2019), which is based on Clover's proprietary Trimer-Tag vaccine technology platform.

Clover SCB-2019 COVID-19 Vaccine Clinical Trials

Phase 2/3 SPECTRA (Study Evaluating Protective-Efficacy and Safety of Clover's Trimeric Recombinant Protein-based and Adjuvanted COVID-19 Vaccine) is a 1:1 randomized, placebo-controlled, double-blinded study to evaluate the efficacy, safety, and immunogenicity of SCB-2019 (CpG 1018/Alum) compared to placebo in over 30,000 participants 18 years of age and older in 31 study sites in the Philippines, Brazil, Colombia, South Africa, and Belgium. Participants received SCB-2019 (CpG 1018/Alum) administered in a two-dose regimen, 21 days apart, or placebo. Efficacy and safety results are reviewed by the independent Data and Safety Monitoring Board, and all COVID-19 cases included in the efficacy analysis were adjudicated by an independent Endpoint Adjudication Committee (EAC).  The SPECTRA study is sponsored by Clover and is funded by CEPI. 

Additional data from the SPECTRA final analysis have been made available in a presentation that can be found on Clover's corporate website. The results will also be submitted for peer-review publication.

Clinical Trial NCT04405908 SCB-2019 as COVID-19 Vaccine - The Phase 1 trial was a randomized, observer-blind, placebo-controlled study to assess the safety, reactogenicity, and immunogenicity of the adjuvanted COVID-19 S-Trimer vaccine candidates formulated with different antigen levels. No serious adverse events related to the vaccine candidates studied were reported. The majority of adverse events were mild and transient. S-Trimer is adjuvanted with GSK's pandemic adjuvant system-induced neutralizing antibody titers (seroconversion) in 100% of participants at the selected 9 µg S-Trimer dose in both adult and elderly groups, with geometric mean titers (GMT) greater than 1:1,800. CpG-1018/alum-adjuvanted S-Trimer induced neutralizing antibodies in 100% of adult participants at the selected 30 µg S-Trimer dose with GMT greater than 1:1,000, and seroconversion was observed in 88% (7 out of 8) in the elderly. Strong Th1 cell-mediated immune responses were also observed for the vaccine candidates with either adjuvant.