A Third Dose of the COVID-19 Vaccine, CVnCoV, Increased the Neutralizing Activity against the SARS-CoV-2 Wild-Type and Delta Variant

Abstract

A third dose of CVnCoV, a former candidate mRNA vaccine against SARS-CoV-2, was previously shown to boost neutralizing antibody responses against SARS-CoV-2 wild-type in adults aged 18−60 and >60 years in a phase 2a clinical study. In the present study, we report the neutralizing antibody responses to a wild-type and a variant of concern, Delta, after a third dose of the vaccine on day (D)57 and D180. Neutralization activity was assessed using a microneutralization assay. Comparable levels of neutralizing antibodies against the wild-type and Delta were induced. These were higher than those observed after the first two doses, irrespective of age or pre-SARS-CoV-2-exposure status, indicating that the first two doses induced immune memory. Four weeks after the third dose on D180, the neutralizing titers for wild-type and Delta were two-fold higher in younger participants than in older participants; seroconversion rates were 100% for wild-type and Delta in the younger group and for Delta in the older group. A third CVnCoV dose induced similar levels of neutralizing responses against wild-type virus and the Delta variant in both naïve and pre-exposed participants, aligning with current knowledge from licensed COVID-19 vaccines that a third dose is beneficial against SARS-CoV-2 variants.

Keywords: COVID-19 vaccine; SARS-CoV-2; delta variant; neutralizing antibodies.

Figure 1

Neutralizing antibody response against wild-type SARS-CoV-2 virus and Delta variant after CVnCoV vaccination. The geometric mean titers (GMTs) of neutralizing antibodies with 95% confidence intervals (CIs) to wild-type (WT; filled circles) and Delta (filled triangles) are shown. (A) Participants aged >60 years with a third dose on Day (D)57 and (B) participants aged 18–60 years and >60 years with a third dose on D180. SARS-CoV-2-naïve (seronegative for N protein throughout the trial period) and SARS-CoV-2-pre-exposed (seropositive for N protein at baseline) participants are indicated by color. The black arrows indicate the days of vaccinations: D1 (baseline), D29 (A,B) and D57 (A) or D180 (B)). n = number of participants with available data per group for all time points. Values above the black-dotted region (≥10) were considered positive.