S-Trimer COVID-19 (SCB-2019) Vaccine Description
S-Trimer COVID-19 vaccine (SCB-2019) is a trimeric SARS-CoV-2 spike (S)-protein subunit vaccine candidate developed by Clover Pharmaceuticals by combining the trimeric SARS-CoV-2 spike (S)-protein with the company’s proprietary Trimer-Tag© technology.
Like other enveloped RNA viruses such as HIV, RSV, and Influenza, SARS-CoV-2 is also an RNA virus with a trimeric spike (S) protein on its viral envelope. The trimeric S protein of SARS-CoV-2 is responsible for binding to host cell surface receptor ACE2 and subsequent viral entry, making it the primary target antigen for vaccine development. The COVID-19 S-Trimer vaccine resembles the native trimeric viral spike protein and is produced via a rapid mammalian cell-culture-based expression system.
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.
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.
On February 1, 2021, Dr. Ralf Clemens, Chairman of the Scientific Advisory Board for Clover’s COVID-19 Vaccine Program, commented in a press release, “This phase 1 dose-finding and adjuvant justification study demonstrated the potential of Clover’s adjuvanted vaccine candidates to bring added value to the global portfolio of COVID-19 vaccines. In both adults and elderly subjects, the vaccine candidates were safe and elicited cellular immune responses and high neutralizing antibody titers with a favorable ratio of neutralizing/binding antibodies. These findings give confidence that Clover’s COVID-19 vaccine candidates are suitable for further clinical development.”
China-based Clover Biopharmaceuticals's protein-based COVID-19 S-Trimer vaccine candidate combined with adjuvants from GSK or Dynavax induces a strong immune response and protection against SARS-CoV-2 in animal models.
S-Trimer COVID-19 Vaccine (SCB-2019) 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.
Clover explores development pathways for the S-Trimer COVID-19 vaccine's accessibility to populations in China and globally if proven to be safe and effective.
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. 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. 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.
Joshua Liang, CEO of Clover Biopharmaceuticals, stated in a press release issued on December 4, 2020: “With positive results from our Phase 1 clinical trial demonstrating strong neutralizing immune responses and favorable safety profiles, we look forward to moving our COVID-19 vaccines into the final stages of clinical development. Combined with our ability to potentially produce more than 1 billion doses of antigen annually and the stability of our vaccines under standard refrigeration conditions, our adjuvanted COVID-19 S-Trimer vaccines are positioned to be well-suited for worldwide distribution."
On March 24, 2021, Joshua Liang, Chief Executive Officer of Clover Biopharmaceuticals, stated in a press release, “Dosing the first participants in SPECTRA marks another significant milestone in our journey to develop a COVID-19 vaccine. There is still a significant need in many global communities for COVID-19 vaccines, and should the Phase 2/3 interim analysis be favorable; we will work closely with regulatory authorities worldwide to make our S-Trimer COVID-19 vaccine candidate available as soon as possible.”
The new CEPI funding announced on November 4, 2020, will also fund 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 allow the production of more than one billion doses annually and build up vaccine inventory, which – if the vaccine is proven to be safe and effective - could be deployed rapidly upon licensure.
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.
S-Trimer COVID-19 Vaccine (SCB-2019) Indication
COVID-19 S-Trimer (SCB-2019) is indicated to prevent SARS-CoV-2 infection, which causes COVID-19 disease.
S-Trimer COVID-19 Vaccine (SCB-2019) 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.
S-Trimer COVID-19 Vaccine (SCB-2019) News
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 protective immunity 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 either 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. 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.
S-Trimer COVID-19 Vaccine (SCB-2019) Clinical Trials
Clinical Trial NCT04405908: SCB-2019 as COVID-19 Vaccine - Last Update Posted: January 12, 2021. Estimated Study Completion Date: May 25, 2021.
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.
Clinical Trial NCT04672395: A Double-Blind, Randomized, Controlled, Phase 2/3 Study to Evaluate the Efficacy, Immunogenicity, and Safety of SCB 2019, a Recombinant SARS-CoV-2 Trimeric S Protein Subunit Vaccine for the Prevention of COVID-19 in 34,000 Participants Aged 18 Years and Older. Last Update Posted on February 18, 2021. Estimated Study Completion Date: July 2022.