S-Trimer (SCB-2019) Protein Subunit Vaccine for COVID-19

Quick Takes

  • SCB-2019 is an S protein subunit SARS-CoV-2 vaccine candidate developed using Trimer-Tag to allow for trimerization of the protein.
  • This phase 1 randomized trial shows SCB-2019 elicits a strong immune response only when combined with an adjuvant such as AS03 or Cpg/Alum.
  • SCB-2019 appears to be well-tolerated and elicits immune responses in both younger and older age groups.

Study Questions:

What is the optimal dose and adjuvant for the S protein subunit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate for eliciting an immune response?


The study was a phase 1, randomized, double-blind placebo-controlled trial in Australia, which enrolled healthy adult volunteers who were randomly allocated to vaccine or placebo. Participants were to receive two doses of SCB-2019 (either 3 μg, 9 μg, or 30 μg) or a placebo (0.9% NaCl) 21 days apart. SCB-2019 either had no adjuvant (S-Trimer protein alone) or was adjuvanted with AS03 or CpG/Alum. Enrollment and analysis were stratified by age group (18-54 years and 55-75 years). All participants were screened for serum antibodies against SARS-CoV-2 and active infection with reverse transcription-polymerase chain reaction (RT-PCR). Reactogenicity was assessed for 7 days after each vaccination and symptoms were recorded in an electronic diary. All unsolicited adverse events were recorded from day 1 to 50. Immune response was assessed on days 1, 22, 36 and 50: humoral responses were measured as SCB-2019 binding IgG antibodies and ACE2-competitive blocking IgG antibodies by enzyme-linked immunosorbent assay (ELISA) (primary endpoint) and as neutralizing antibodies by wild-type SARS-CoV-2 microneutralization assay. Cellular responses to pooled S-protein peptides were measured by flow-cytometric intracellular cytokine staining.


A total of 148 participants (mean age of 36 in the younger group with 40% male, and mean age of 61 years for the older group with 47% male) were included in this analysis. Vaccination was well tolerated, with two grade 3 solicited adverse events (cellulitis after a cat bite in 9 μg AS03-adjuvanted and hyponatremia in the 9 μg CpG/Alum-adjuvanted groups). Most local adverse events were mild injection-site pain, and local events were more frequent with SCB-2019 formulations containing AS03 adjuvant (44–69%) than with those containing CpG/Alum adjuvant (6–44%) or no adjuvant (3–13%). Systemic adverse events were more frequent in younger adults (38%) than in older adults (17%) after the first dose, but increased to similar levels in both age groups after the second dose (30% in older and 34% in younger adults). SCB-2019 with no adjuvant elicited minimal immune responses (three seroconversions by day 50), but SCB-2019 with fixed doses of either AS03 or CpG/Alum adjuvants induced high titers and seroconversion rates of binding and neutralizing antibodies in both younger and older adults (anti-SCB-2019 IgG antibody geometric mean titers at day 36 were 1567–4452 with AS03 and 174–2440 with CpG/Alum). Titers in all AS03 dose groups and the CpG/Alum 30 μg group were higher than were those recorded in a panel of convalescent serum samples from patients with COVID-19. Both adjuvanted SCB-2019 formulations elicited T-helper-1-biased CD4+ T-cell responses. Overall, immune responses across all assays correlated well.


The SCB-2019 vaccine formulated with either AS03 or CpG/Alum adjuvants were well tolerated and elicited robust humoral and cellular immune responses against SARS-CoV-2.


The main challenge in producing a protein subunit candidate vaccine is in maintaining the adequate confirmation of the antigen in order to elicit an immune response specific to the original viral protein. The main viral antigenic target of SARS-CoV-2 is the glycosylated spike (S) protein, a trimeric protein consisting of two subunits (S1 and S2) that is essential for viral binding, fusion, and uptake into mammalian cells. Trimer-Tag (Clover Biopharmaceuticals, Chengdu, China) is derived from the C-terminal region of human type I procollagen and is capable of self-trimerization. When biologically active proteins are fused in-frame to Trimer-Tag, the resulting fusion proteins expressed in cells are secreted as disulphide bond-linked homotrimers. S-Trimer is a recombinant SARS-CoV-2 fusion protein produced using Trimer-Tag technology in Chinese hamster ovary cells. It preserves the native trimeric structure of S-protein in the prefusion form of the antigenic epitope, which binds with high affinity to human ACE2 and is necessary for viral neutralization. This phase 1 trial tests the resultant SCB-2019 vaccine with and without AS03 or SpG/Alum adjuvants. Rate of adverse effects was lower than similar vaccines, and the magnitude of the immune response appears to be similar to that of the mRNA-based vaccines with established efficacy. SCB-2019 on the other hand is stable in liquid solution formulations at 2–8°C for at least 6 months, which would theoretically facilitate storage and deployment. Overall, these findings are encouraging and portend the addition of yet another vaccine to the armamentarium against SARS-CoV-2.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Heart Failure and Cardiac Biomarkers

Keywords: Antibodies, Neutralizing, CD4-Positive T-Lymphocytes, Cellulitis, COVID-19, Cytokines, Hyponatremia, Immunity, Cellular, Immunoglobulin G, Peptidyl-Dipeptidase A, Polymerase Chain Reaction, Protein Subunits, Primary Prevention, Reverse Transcription, severe acute respiratory syndrome coronavirus 2, Vaccination, Vaccines

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