Prediction of long-term kinetics of vaccine-elicited neutralizing antibody and time-varying vaccine-specific efficacy against the SARS-CoV-2 Delta variant by clinical endpoint

Background Evidence on vaccine-specific protection over time, in particular against the Delta variant, and protection afforded by a homologous third dose is urgently needed. Methods We used a previously published model and neutralization data for five vaccines—mRNA-1273, BNT162b2, NVX-CoV2373, V01, and CoronaVac— to evaluate long-term neutralizing antibody dynamics and predict time-varying efficacy against the Delta variant by specific vaccine, age group, and clinical severity. Results We found that homologous third-dose vaccination produces higher neutralization titers compared with titers observed following primary-series vaccination for all vaccines studied. We estimate the efficacy of mRNA-1273 and BNT162b2 against Delta variant infection to be 63.5% (95% CI: 51.4–67.3%) and 78.4% (95% CI: 72.2–83.5%), respectively, 14–30 days after the second dose, and that efficacy decreases to 36.0% (95% CI: 24.1–58.0%) and 38.5% (95% CI: 28.7–49.1%) 6–8 months later. Fourteen to 30 days after administration of homologous third doses, efficacy against the Delta variant would be 97.0% (95% CI: 96.4–98.5%) and 97.2% (95.7–98.1%). All five vaccines are predicted to provide good protection against severe illness from the Delta variant after both primary and homologous third dose vaccination. Conclusions Timely administration of third doses of SARS-CoV-2-prototype-based vaccines can provide protection against the Delta variant, with better performance from mRNA vaccines than from protein and inactivated vaccines. Irrespective of vaccine technology, a homologous third dose for all types of vaccines included in the study will effectively prevent symptomatic and severe COVID-19 caused by the Delta variant. Long-term monitoring and surveillance of antibody dynamics and vaccine protection, as well as further validation of neutralizing antibody levels or other markers that can serve as correlates of protection against SARS-CoV-2 and its variants, are needed to inform COVID-19 pandemic responses.