1. Novel SARS-CoV-2 vaccine SCB-2019 was well-tolerated amongst both younger and older adults.
2. SCB-2019 adjuvanted with AS03 or CpG/Alum elicited strong humoral and cellular responses.
Evidence Rating Level: 1 (Excellent)
Study Rundown: As the global pandemic of SARS-CoV-2 (COVID-19) continues to ravage healthcare systems around the world, the effort to produce an efficacious and safe vaccine is ongoing. There are currently over 64 vaccines undergoing accelerated development worldwide. The S-Trimer protein, a recombinant fusion protein from COVID-19, binds to human ACE2 with high affinity and preserves the structure of the S protein that is the principal viral antigenic target in most vaccines. This phase 1, randomized, double-blind placebo-controlled trial sought to evaluate the safety and immunogenicity of SCB-2019, a vaccine candidate produced from purified S-Trimer protein, with no adjuvant or adjuvanted with either the emulsion AS03 or the TLR9 agonist CpG and chemical compound Alum (CpG/Alum). Overall, SCB-2019 had a favorable safety profile with few serious adverse events across groups. SCB-2019 without adjuvant produced fewer systemic adverse events than with either AS03 or CpG/Alum. The most frequent reported adverse events were headaches, fatigue and myalgias, and the vast majority were grade 1-2. No significant laboratory safety abnormalities were noted in any group during the study. The frequency of reported adverse events was overall greater in younger vs. older participants. Seroconversion for anti-SCB-2019 IgG antibodies was overall low for the non-adjuvanted SCB-2019, regardless of dose level. In contrast, all participants in the AS03 adjuvant group seroconverted by day 36, and more modest seroconversion occurred in the CpG/Alum adjuvant group. ACE2 receptor-competitive blocking antibodies were not seen with SCB-2019 alone, but both AS03- and CpG/Alum-adjuvanted had robust responses. Neutralizing antibodies to wild-type SARS-CoV-2 followed a similar pattern to IgG seroconversion. An important limitation of this study is its relatively small sample size, with most groupings of participants containing only 7-15 individuals, making it important to temper any interpretation about the experiencing of adverse events with caution.
Click to read the study in The Lancet
Click to read an accompanying editorial in The Lancet
Relevant Reading: S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates
In-Depth [randomized controlled trial]: This phase 1, randomized, double-blind placebo-controlled trial took place in one center in Perth, Australia, and enrolled a total of 151 participants in younger (18-54 years old) and older (55-75 years old) age groups. Primary endpoints were the assessment of safety, tolerability and immunogenicity of SCB-2019 alone and with either the AS03 of CpG/Alum adjuvant. Patients were randomized to receive either SCB-2019 alone, with AS03, with CpG/Alum, or placebo at three different doses (3ug, 9ug and 30ug). After vaccination, participants were told to record any experienced adverse events for 7 days, at which point they were seen again. In the non-adjuvanted SCB-2019 group, systemic adverse events were mild in the 3ug and 9ug group (13% per group; one of eight), however were higher in the 30ug group (4 of 8). Fewer events occurred after the second dose. Systemic adverse events were overall higher and not dose-dependent for the SCB-2019-AS03 adjuvant groups; 44-56% of participants reported events after the second dose. Those in the SCB-2019-CpG/Alum group reported an intermediate number of adverse events (13-31% after second dose). By day 50 post-vaccination with SCB-2019 alone, one patient in the 3ug (13%) and two in the 30ug group (29%) had seroconverted with anti-SCB-2019 IgG antibodies. In contrast, all participants in the AS03 group seroconverted by day 36, and, in the CpG/Alum group, seroconversion rates reached 87.5-93.8% at day 50. No increase in neutralizing activity of wild-type SARS-Cov-2 was seen in SCB-2019 alone across all dose levels, whereas SCB-2019 with AS03 had strong dose-dependent increases in neutralizing activity. Dose dependent responses were also seen in the CpG/Alum group, albeit of smaller magnitude. Titers were maintained up until day 50, the last day of the interim analysis.
Image: PD
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