The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in more than 600 million confirmed cases and 6.5 million deaths worldwide.
mRNA-based vaccines have emerged as a leading platform for COVID-19 protection and are extensively investigated in basic and clinical trials. SYS6006 (CSPC Pharmaceutical Group) is a newly investigational COVID-19 mRNA vaccine encoding a full-length S protein sequence of the prototype SARS-CoV-2 strain and incorporating the key mutations of main epidemic variants.
In March 2023, it has been authorized for emergent use in China by the national medicinal product agency (NMPA) of China. Yet, the data from clinical trials have not been published before. Moreover, the third dose of inactivated vaccine of COVID-19 has been proposed as the initial boosting regimen, and the second heterologous booster (the fourth dose of the vaccine) is worth investigating.
By enrolling eligible healthy subjects and convalescent COVID-19 patients, researchers from Shanghai Xuhui Central Hospital have worked and unveiled the first clinical safety and efficacy profile of SYS6006.
Eighteen eligible participants, who had completed three doses of inactivated COVID-19 vaccines, received a fourth boosting dose of SYS6006-20 μg. Eighteen convalescent COVID-19 patients were enrolled for the collection of serum samples as a comparator of immunogenicity.
The incidence of adverse events within 30 days after the boosting was collected and reported. The titers of anti-RBD antibodies of the Omicron strain (BA.2 and BA.4/5) in serum and titers of neutralizing antibodies against pseudovirus of the Omicron strain (BA.2 and BA.4/5) were evaluated from baseline (day 0) until day 180 post-vaccination.
Besides, specific T-cell responses against SARS-CoV-2 were measured by detecting the production of interferon gamma (IFN-γ) positive spots with ELISpot assay. This study entitled "Safety and immunogenicity of a modified COVID-19 mRNA vaccine, SYS6006, as a fourth-dose booster following three doses of inactivated vaccines in healthy adults: an open-labeled phase 1 trial" is published online in Life Metabolism in 2023.
In this study, no serious adverse events were reported within 30 days after vaccination. No Grade 3 fever or serious adverse event was reported in the SYS6006 group. Notably, SYS6006 elicited higher titers and longer increases in anti-RBD antibodies and neutralizing antibodies (>90 days) compared with the convalescent group (P <0.0001) against Omicron strain (BA.2 and BA.4/5). Besides, higher positive spots of T-cell-secreting IFN-γ were observed in the SYS6006 group than those in the convalescent group (P <0.05).
These results demonstrated that a modified mRNA vaccine SYS6006 was safe and highly immunogenic as a heterologous booster in healthy Chinese adults. The strong enhancement of antibody titers after heterologous boosting is encouraging, along with the broad-spectrum neutralizing activity of these antibodies against variants of concern, such as Omicron BA.2 and BA.4/5.
The titers in the SYS6006 group were higher than those in the convalescent patients. These findings suggest the flexible use of the mRNA vaccine as a booster regimen, which could accelerate the end of the pandemic.
Gui, Y., et al. (2023) Safety and immunogenicity of a modified COVID-19 mRNA vaccine, SYS6006, as a fourth-dose booster following three doses of inactivated vaccines in healthy adults: an open-labeled Phase 1 trial. Life Metabolism. doi.org/10.1093/lifemeta/load019.