Persistence of the Immune Responses and Cross-Neutralizing Activity With Variants of Concern Following 2 Doses of Adjuvanted SCB-2019 Coronavirus Disease 2019 Vaccine

Abstract

Background: We have previously reported the safety and immunogenicity 4 weeks after 2 doses of the Clover coronavirus disease 2019 (COVID-19) vaccine candidate, SCB-2019, a stabilized prefusion form of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S-trimer). We now report persistence of antibodies up to 6 months after vaccination, and cross-neutralization titers against 3 variants of concern (VoCs).

Methods: In a phase 1 study, adult (18-54 years of age) and elderly (55-75 years of age) volunteers received 2 vaccinations 21 days apart with placebo or 3-, 9-, or 30-µg. We measured immunoglobulin G (IgG) antibodies against SCB-2019, angiotensin-converting enzyme 2 (ACE2) competitive binding antibodies, and neutralizing antibodies against wild-type SARS-CoV-2 (Wuhan-Hu-1) at days 101 and 184, and neutralizing antibodies against 3 VoCs, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1), in day 36 sera.

Results: Titers waned from their peak at days 36-50, but SCB-2019 IgG antibodies, ACE2 competitive binding antibodies, and neutralizing antibodies against wild-type SARS-CoV-2 persisted at 25%-35% of their observed peak levels at day 184. Day 36 sera also demonstrated dose-dependent increases in neutralizing titers against the 3 VoCs.

Conclusions: SCB-2019 dose-dependently induced immune responses against wild-type SARS-CoV-2, which persisted up to day 184. Neutralizing antibodies were cross-reactive against 3 of the most prevalent VoCs.

Keywords: COVID-19; immunogenicity; persistence; vaccine; variants of concern.

Figure 1.

Immune responses to vaccinations at days 1 and 22 of the 3 different doses of SCB-2019 + CpG/alum (3 µg in blue, 9 µg in yellow, and 30 µg in red) in adult (left panels) and elderly (right panels) groups assessed by wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies (top panels), anti–SCB-2019 immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (middle panels), and angiotensin-converting enzyme 2 (ACE2) competitive binding antibodies (lower panels). Values show geometric mean titers per group (n = 7 or 8) with 95% confidence bars at each timepoint. Also shown is the mean value in each assay determined in human convalescent sera (HCS) obtained 20–57 days after symptom onset. Gray shading represents 95% confidence interval.

Figure 2.

Pairwise Pearson regression analyses between the individual data obtained for the 3 different assays in the adult and elderly participants who received SCB-2019 + CpG/alum obtained at day 184. Abbreviations: Abs, antibodies; ACE2, angiotensin-converting enzyme 2; CI, confidence interval; EC₅₀, ELISA concentration; IgG, immunoglobulin G; MN₅₀, microneutralization titer.

Figure 3.

Neutralizing immune responses against the original severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Wuhan-Hu-1) and 3 variants of concern (Alpha, Beta, and Gamma) in day 36 sera after 3 different dosages of SCB-2019 adjuvanted with CpG/alum were administered on days 1 and 22 to adult (18–54 years) and elderly (55–75 years) participants, and World Health Organization (WHO) human convalescent sera International Standard 20/136. Circles show individual titers; columns are geometric mean titers (GMTs; microneutralization titer [MN₅₀]) with 95% confidence intervals.