Vaccine Info

Clover SCB-2019 COVID-19 Vaccine

Authored by
Staff
Last reviewed
June 30, 2022
Share

Clover SCB-2019 COVID-19 Vaccine 2022

Clover Biopharmaceutical COVID-19 vaccine (SCB-2019, CpG 1018/Alum) is a trimeric SARS-CoV-2 virus spike (S)-protein subunit vaccine candidate developed by Clover 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 a 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) and enveloped RNA virus antigens responsible for entry into host cells. Thus, Trimer-Tag may be an essential platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses, as stated 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 were variants observed in the efficacy analysis. 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 trial's primary endpoint.

On April 18, 2022, The Lancet published 'Impact of previous exposure to SARS-CoV-2 and S-Trimer (SCB-2019) COVID-19 vaccination on the risk of reinfection: a randomized, double-blinded, placebo-controlled, phase 2 and 3 trial.' Previous exposure to SARS-CoV-2 decreased the risk and severity of subsequent COVID-19 infection, even against newly emerging variants. One or two doses of SCB-2019 further enhance protection.

New clinical data adds to the growing body of evidence supporting the potential use of SCB-2019 (CpG 1018/Alum) as a universal COVID-19 booster vaccine “This highly encouraging homologous booster data against Omicron represents a key milestone on Clover’s path to developing SCB-2019 for primary vaccination and as a universal COVID-19 booster vaccine to protect individuals in need, regardless of previous vaccination technology or infection history,” said Joshua Liang, CEO and Executive Director of Clover, in a press release issued on June 27, 2022. 

Clover plans to submit conditional regulatory approval applications to the EMA, the NMPA, and the WHO. Pending WHO Emergency Use Listing, Clover will supply up to 414 million vaccine doses to the COVAX Facility for equitable distribution. SCB-2019 - DrugBank Accession Number: DB15805.

Clover Biopharmaceuticals, Ltd. (Clover; Stock code: 2197.HK), is a global clinical-stage biotechnology company located in CHENGDU, China developing novel vaccines and biological therapeutic candidates.

Clover 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.

On November 3, 2020, CEPI extended its partnership with Clover Biopharmaceuticals to fund the COVID-19 vaccine candidate through a 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 nine 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.

The Lancet published an article on January 29, 2021 - 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. Study Results Interpretation: The SCB-2019 vaccine, comprising S-Trimer protein formulated with 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.

On September 22, 2021, Clover Biopharmaceuticals, Ltd. and CEPI announced 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 were variants observed in the efficacy analysis. SCB-2019 (CpG 1018/Alum) revealed 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 trial's primary endpoint. 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 (Clover; HKEX: Stock code: 2197.HK), focused on discovering and developing transformative biologic therapies and vaccines.

Clover SCB-2019 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 Boosters

Clover Biopharmaceuticals announced on June 27, 2022, new positive clinical data in individuals vaccinated with the third dose of SCB-2019 demonstrated a significant, 19-fold increase in neutralizing antibody levels against the Omicron BA.2 variant compared to pre-booster levels among baseline seronegative participants. Clinical trials are ongoing to evaluate SCB-2019 (CpG 1018/Alum) as a universal COVID-19 booster vaccine.

Clover SCB-2019 Storage

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, based on current results, Clover's COVID-19 vaccine candidates' ability to be stored in standard refrigeration temperatures makes them suitable for broad global distribution.

Clover SCB-2019 News 2021-2022

June 27, 2022 - Clover Bio announced new positive data adds to the growing body of evidence supporting the potential use of SCB-2019 (CpG 1018/Alum) as a universal COVID-19 booster vaccine. Dr. Nicholas Jackson, President of Global Research and Development of Clover, stated: "As part of our universal booster development for SCB-2019, we look forward to sharing additional clinical data, including top-line head-to-head data comparing SCB-2019 as a heterologous, 3rd booster dose against homologous 3rd booster doses of CoronaVac™ and Comirnaty® in Q3 2022."

June 13, 2022 - Clover Biopharmaceuticals, Ltd. announced the first participants had been dosed in a Phase 3 study evaluating the safety and immunogenicity of Clover's SCB-2019 vaccine candidate as a COVID-19 booster in individuals who were previously vaccinated with CoronaVac™, Comirnaty®, or Vaxzevria® vaccines. 

April 19, 2022 - Clover Biopharmaceuticals, Ltd. announced additional positive data from two ongoing studies evaluating SCB-2019 (CpG 1018/Alum), which demonstrated durable protection through approximately six months following primary vaccination and robust immune responses in neutralizing Omicron and other variants of concern after a booster dose in an expanded data set involving over 100 participants.

February 14, 2022 - Clover Biopharmaceuticals, Ltd. provided an update on corporate developments and the development of a universal COVID-19 vaccine. Joshua Liang, Chief Executive Officer and Executive Director of Clover, stated, "Our immediate priorities are to expedite global conditional approvals of our protein-based COVID-19 vaccine candidate and complete its development as a universal COVID-19 vaccine booster.

January 21, 2022 - Clover Biopharmaceuticals, Ltd. announced that final efficacy data from SPECTRA, a global Phase 2/3 clinical trial, is evaluating the efficacy, safety, and immunogenicity of its COVID-19 vaccine candidate, SCB-2019 (CpG 1018/Alum), has been published in the peer-reviewed journal, The Lancet. The paper, 'Efficacy of the adjuvanted subunit protein Covid-19 vaccine, SCB-2019: a phase 2/3 multicentre, double-blind, randomized, placebo-controlled trial.' This ongoing study showed vaccine efficacy of 67·2% (95·72% CI 54·3–76·8) against any severity of RT-PCR-confirmed COVID-19 and 83·7% (97·86% CI 55·9–95·4) efficacy against moderate-to-severe COVID-19 in the per-protocol population of participants without previous exposure to SARS-CoV-2. Efficacy against hospital admission was 100%, and there were no COVID-19-related deaths in the vaccine group. Two doses of SCB-2019 vaccine plus CpG and alum provide notable protection against the severity spectrum of COVID-19 caused by circulating SAR-CoV-2 coronaviruses, including the predominating delta variant.

January 5, 2022 - Clover Biopharmaceuticals, Ltd. announced that the first participants had been dosed with Clover's COVID-19 vaccine candidate, SCB-2019 (CpG 1018/Alum), as a homologous booster dose following primary vaccination of SCB-2019 (CpG 1018/Alum) in the ongoing global Phase 2/3 SPECTRA clinical trial. 

November 18, 2021 - Clover Biopharmaceuticals and CEPI announced that CEPI would provide up to an additional US$36.9 million in funding to support the continued development of SCB-2019 through licensure. This brings CEPI's total potential funding in SCB-2019 to up to US$397.4 million.

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 a 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 is 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.

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 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 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 commenced production planning for 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 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 Announced 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.

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).

Clover SCB-2019 COVID-19 Vaccine Clinical Trials

Announced on June 13, 2022, the Phase 3 trial is a double-blind, randomized, controlled study that will evaluate the safety and immunogenicity of SCB-2019 (CpG 1018/Alum) administered as a booster dose in individuals who received two doses of CoronaVac™, Comirnaty®, or Vaxzevria®. In addition, individuals receiving a homologous booster dose of CoronaVac™, Comirnaty®, or Vaxzevria®, will be used as controls compared to the heterologous SCB-2019 (CpG 1018/Alum) booster dose. Initial data for the key third dose booster groups (CoronaVac™, Comirnaty®) are expected in Q3-2022, and third dose booster data in the Vaxzevria® group is expected in Q4-2022. In addition, Clover also plans to initiate a subcohort evaluating SCB-2019 (CpG 1018/Alum) as a fourth dose booster in individuals previously receiving three doses of CoronaVac™, with initial results expected in Q4-2022. The study will enroll over 1,200 adult & elderly participants in the Philippines.

On January 20, 2022, results from the SPECTRA study were published: Interpretation - Two doses of SCB-2019 vaccine plus CpG and alum provides notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 coronaviruses, including the predominating delta variant.

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. 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, 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.