Both the AS03 and CpG/Alum adjuvant formulations of the SCB-2019 vaccine produced by Clover Biopharmaceuticals was safe for use and showed high viral neutralizing activity against COVID-19. These results were published in The Lancet.
This phase 1, randomized, double-blind, placebo-controlled trial (Clinicaltrials.gov Identifier: NCT04405908) was conducted at the Linear Clinical Research center in Australia. The SCB-2019 vaccine was comprised of a trimeric form of the spike protein (S-Trimer) formulated with either CpG 1018 with Alum adjuvant or AS03 preparations.
Participants (N=151) were randomized to receive SCB-2019 (either 3 µg [n=40], 9 µg [n=40], or 30 µg [n=41]) or placebo (n=30; 0.9% NaCl) 21 days apart. Within each vaccine recipient group, participants were randomized in a 1:2:2 ratio to receive the vaccine with no adjuvant (COVID-19 S-Trimer protein alone), with AS03, or with CpG/Alum. Participants were stratified by age prior to randomization and all participants aged 55-75 years received the vaccine with adjuvant.
Participants in the younger age group (18-54 years) were 40% men, 79% White, and were a mean age of 36.2 and 32.6 years for the vaccine and placebo recipients, respectively. The older age group (55-75 years) included 47% men, 100% White, and a mean age of 61.1 and 62.3 years for the vaccine and placebo recipients, respectively.
At the conclusion of the study (follow-up day 50), no deaths or hospitalizations were reported. There were no serious adverse events reported in either group associated with the vaccine.
Recipients of the vaccines with either adjuvant preparations reported grade 1 or 2 local adverse events. These events increased after the second dose and escalated to include 2 cases of grade 3 pain. Younger adults reported more pain compared with older adults after the first dose (39% vs 21%) but not after the second dose (35% vs 34%), respectively.
At day 50, 3 recipients of the SCB-2019 non-adjuvanted vaccine had detectable immunoglobulin (Ig)G antibodies.
Among the AS03 recipients, all participants seroconverted by day 36. Following the second dose, these participants had increases to their geometric mean titer (GMT; younger adults: range, 2510-4452; older adults: range, 1567-3625) which surpassed those observed among convalescent serum. At day 50, IgG antibody titers persisted at high levels.
Among CpG/Alum recipients, GMTs were 478-2440 among the younger adults and 174-572 among the older adults at day 36. At day 50 seroconversion rates were 87.5%-93.8%.
Compared with convalescent serum, samples from SCB-2019 vaccinated individuals exhibited correlated angiotensin-converting enzyme (ACE2)-competitive blocking antibodies with IgG antibodies (R, 0.88; P <.0001), IgG antibodies with wild-type microneutralization assay (WT-MN50; R, 0.70; P <.0001), and ACE-2-competitive blocking antibodies with WT-MN50 (R, 0.67; P <.0001).
This study was limited by its sample sizes which only allowed for robust assessment of safety and tolerability and not age-dependent effects.
These findings suggested that 9 mg of SCB-2019 with AS03 or 30 mg SCB-2019 with CpG/Alum were safe candidates for vaccination against COVID-19.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Richmond R, Hatchuel L, Dong M, et al. Safety and immunogenicity of S-Trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: a phase 1, randomised, double-blind, placebo-controlled trial. Lancet. 2021;S0140-6736(21)00241-5. doi:10.1016/S0140-6736(21)00241-5.