Safety and immunogenicity of VLPCOV-02, a SARS-CoV-2 self-amplifying RNA vaccine with a modified base, 5-methylcytosine, in healthy individuals (preprint)

Continuing emergence of variants of concern resulting in reduced SARS-CoV-2 vaccine efficacy necessitates additional prevention strategies. The structure of VLPCOV-01, a lipid nanoparticle-encapsulated, self-amplifying RNA COVID-19 vaccine with a comparable immune response to BNT162b2, was revised by incorporating a modified base, 5-methylcytosine to reduce reactogenicity, and an updated receptor-binding domain derived from Brazil (gamma) variant. Interim analyses of a phase 1 dose-escalation booster vaccination study with the resulting construct, VLPCOV-02, in healthy, previously vaccinated Japanese individuals (N=96) are reported (jRCT2051230005). A dose-related increase in solicited local and systemic adverse events was observed, which were generally rated mild or moderate. The most commonly occurring events were tenderness, pain, fatigue, and myalgia. Serum SARS-CoV-2 immunoglobulin titers increased during the 4 weeks post-immunization. VLPCOV-02 demonstrated a favorable safety profile compared with VLPCOV-01, with a lower frequency of adverse events and fewer fever events at an equivalent dose. These findings support further study of VLPCOV-02.

Estimating immunity with mathematical models for SARS-CoV-2 after COVID-19 vaccination (preprint)

Antibody waning after COVID-19 vaccinations results in the necessity of booster shots. Determining the timing of booster shots according to the decreasing antibodies of each individual will reduce the burden of excessive vaccine administration. We have developed a mathematical model to estimate waning antibody concentration (titer) during the timecourse after two doses of BNT162b2 vaccine. Using consecutive antibody datasets of over 600 vaccinated healthcare workers, we demonstrated a two-compartment model that fits better than other models. Internal validation of the model demonstrated 97.0% accuracy and external validation of healthcare worker and hemodialyzed patient datasets demonstrated 98.2% and 83.3% accuracy, respectively. A smart device application developed using our model can rapidly calculate the timing of negative seroconversion with a single antibody titer measurement. Although further modification of the model is essential, the change in antibody titer over time from COVID-19 vaccination may be estimated with a two-compartment model.