Clover COVID-19 Vaccine 2023
Clover Biopharmaceutical Ltd. SCB-2019 (CpG 1018/Alum) COVID-19 vaccine is a trimeric SARS-CoV-2 coronavirus spike (S)-protein subunit vaccine developed with the company's proprietary Trimer-Tag© technology. The 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 COVID-19 vaccines.
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) 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. 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.
On August 25, 2022, Clover announced positive data from a global Phase 2/3 trial that met the primary endpoint and demonstrated that vaccination with SCB-2019 elicited approximately 2-fold higher neutralizing antibody titers in adolescents compared to young adults (aged 18 to 25 years). In this population, SCB-2019 had previously been demonstrated to be highly protective against COVID-19. Then on November 30, 2022, Clover announced a collaboration with the International Vaccine Institute that Clinical Infectious Diseases had published additional data from SPECTRA, which showed that a household contact was 84% less likely to get a SARS-CoV-2 infection when the infected household member had received SCB-2019 compared to placebo.
Clover's contract development and manufacturing organization received a European Union Good Manufacturing Practice certificate on September 20, 2022, to produce SCB-2019 vaccines. In addition to its ongoing submissions to the China National Medical Products Administration (NMPA), the European Medicines Agency (EMA), and the World Health Organization (WHO) to broaden the potential use of SCB-2019 across age groups and as a universal COVID-19 booster vaccine. Pending WHO Emergency Use Listing, Clover anticipates supplying about 400 million vaccine doses to the COVAX Facility for equitable distribution. And SCB-2019 (CpG 1018/Alum) anticipates receiving emergency use authorization (EUA) in at least one additional country and completing multiple EUA submissions during H1 2023.
On February 14, 2023, Clover announced that the commercial launch of its COVID-19 vaccine in the People’s Republic of China began with the first doses delivered and administered in Changxing, Zhejiang, as part of China’s national second booster dose (fourth vaccination dose) campaign targeting older adults, immunocompromised individuals and individuals with comorbidities.
SCB-2019 - DrugBank Accession Number: DB15805. Clover: SCB-2019 clinical trial tracker.
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 Vaccine Price
The price for the Clover SCB-2019 vaccine has yet to be announced.
Clover Biopharmaceuticals announced positive data from its ongoing Phase 3 study evaluatiClover'sr’s SCB-2019 as a universal COVID-19 booster vaccine candidate. The data showed that SCB-2019 elicited superior levels of neutralizing antibodies against the Omicron BA.5 subvariant, the dominant SARS-CoV-2 variant circulating globally when administered as a third heterologous dose in participants who previously received two doses of an inactivated vaccine compared to a third dose of the inactivated vaccine.
Clover Vaccine History
Preclinical data have shoClover'sr'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 in 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 of CEPI's total investment, 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.
Joshua Liang is the co-inventor of the COVID-19 S-Trimer vaccine.
Clover Vaccine Storage
Preliminary results from stability studies demonstrated that S-Trimer is stable at 2-8o C for at least six months (longer-term stability studies are ongoing) and stable at room temperature and 40o C for at least one month, respectively, in line with the adjuvants tested.
Clover COVID-19 Vaccine News 2021-2023
February 14, 2023 - Clover Biopharmaceuticals, Ltd. announced Joshua Liang, Chief Executive Officer, and Executive Director, stated, “I would like to sincerely thank everyone who contributed to making today’s launch possible, including our employees, clinical trial investigators, and participants, health authorities in China and around the world, and our CEPI partners who provided instrumental technical and funding support.”
January 15, 2023 - “Clover transformed into a commercial-stage, vaccines-focused biotech company with proven R&D capabilities in 2022. In 2023, we are focused on launching our vaccine in multiple countries and working with health authorities in China and globally to increase booster coverage for vulnerable populations,” said Joshua Liang, CEO and Executive Director of Clover.
November 30, 2022"- “These results are important for public health officials striving to control future outbreaks and indicate that vaccination with SCB-2019 considerably reduces the risk of SARS-CoV-2 spreading within communities "s,” said Dr. Nicholas Jackson, President of Global Research and Development of Clove.
August 30, 2022 - Clover Biopharmaceuticals, Ltd. announced positive Phase 2/3 clinical trial data demonstrating that its lead COVID-19 vaccine candidate, SCB-2019 elicited a robust immune response to Omicron BA.5 subvariant, building upon previously announced results for neutralization against Omicron BA.2 and BA.1.
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.
June 30, 2021 - Clover Biopharmaceuticals and Dynavax Technologies Corporation announced the execution of a commercial supply agreement for Dynavax's CpG 1018TM advanced adjuvant for the use of Clover's protein-based COVID-19 vaccine.
March 1, 2021 - The journal Nature published a 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 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.
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.
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 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.'
June 19, 2020 - Clover Biopharmaceuticals announced that the first participants had been dosed in Phase 1 first-in-human study evaluating tcompany'sy's COVID-19 S-Trimer subunit vaccine candidate (SCB-2019).
Clover SCB-2019 COVID-19 Vaccine Clinical Trials
On August 30, 2022, in this Phase 2/3 trial, a homologous booster dose of SCB-2019 (CpG 1018/Alum) in individuals who previously received two doses of SCB-2019 (CpG 1018/Alum) induced a robust and rapid neutralizing antibody immune response (using validated live SARS-CoV-2 virus neutralization assays). In addition, a cohort comprised of individuals who were baseline seronegative (individuals with no evidence of natural infection using anti-N antibody testing and observed waning neutralizing antibody levels after the second dose and before the booster dose) demonstrated a robust 12-fold increase against the Omicron BA.5 subvariant with geometric mean titers (GMTs) of neutralizing antibodies increasing from 35 (pre-booster) to 408 (14 days post-booster). In addition, we previously released results from this study demonstrating that, relative to pre-booster levels, a third dose of SCB-2019 (CpG 1018/Alum) exhibited a 19-fold boost in neutralizing antibodies against the Omicron BA.2 subvariant (GMTs: 25 [pre-booster], 469 [post-booster]) and a 12-fold boost in neutralizing antibodies against Omicron BA.1 (GMTs: 18, 211. Together, this data supports the potential of SCB-2019 (CpG 1018/Alum) as a broadly neutralizing vaccine against divergent lineages of the Omicron variant.
Announced on June 13, 2022, the Phase 3 trial is a double-blind, randomized, controlled study evaluating 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 Clover'sr'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 available in a presentation on Clover'sr'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 wiGSK'sK'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, 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.