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.
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.
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