Second booster dose improves antibody neutralization against BA.1, BA.5 and BQ.1.1 in individuals previously immunized with CoronaVac plus BNT162B2 booster protocol

Abstract

Introduction: SARS-CoV-2 vaccines production and distribution enabled the return to normalcy worldwide, but it was not fast enough to avoid the emergence of variants capable of evading immune response induced by prior infections and vaccination. This study evaluated, against Omicron sublineages BA.1, BA.5 and BQ.1.1, the antibody response of a cohort vaccinated with a two doses CoronaVac protocol and followed by two heterologous booster doses.

Methods: To assess vaccination effectiveness, serum samples were collected from 160 individuals, in 3 different time points (9, 12 and 18 months after CoronaVac protocol). For each time point, individuals were divided into 3 subgroups, based on the number of additional doses received (No booster, 1 booster and 2 boosters), and a viral microneutralization assay was performed to evaluate neutralization titers and seroconvertion rate.

Results: The findings presented here show that, despite the first booster, at 9m time point, improved neutralization level against omicron ancestor BA.1 (133.1 to 663.3), this trend was significantly lower for BQ.1.1 and BA.5 (132.4 to 199.1, 63.2 to 100.2, respectively). However, at 18m time point, the administration of a second booster dose considerably improved the antibody neutralization, and this was observed not only against BA.1 (2361.5), but also against subvariants BQ.1.1 (726.1) and BA.5 (659.1). Additionally, our data showed that, after first booster, seroconvertion rate for BA.5 decayed over time (93.3% at 12m to 68.4% at 18m), but after the second booster, seroconvertion was completely recovered (95% at 18m).

Discussion: Our study reinforces the concerns about immunity evasion of the SARS-CoV-2 omicron subvariants, where BA.5 and BQ.1.1 were less neutralized by vaccine induced antibodies than BA.1. On the other hand, the administration of a second booster significantly enhanced antibody neutralization capacity against these subvariants. It is likely that, as new SARS-CoV-2 subvariants continue to emerge, additional immunizations will be needed over time.

Keywords: SARS-CoV-2; antibody neutralization; booster; omicron; vaccination; variants.

Figure 1

Schematic of vaccination and samples collection.

Figure 2

Viral microneutralization assay against omicron sublineages to evaluate neutralization titers (VNT₅₀) and seroconvertion rate. (A) VNT₅₀ for samples collected 9 months after CoronaVac 2 doses protocol. (B) VNT₅₀ for samples collected 12 months after CoronaVac 2 doses protocol; (C) VNT₅₀ for samples collected 18 months after CoronaVac 2 doses protocol. Vaccination subgroups are represented in green (No booster), blue (1 booster) and pink (2 boosters). VNT₅₀ means, for each group, are highlighted under the graphs. Dashed lines represent the seroconvertion dilution cutoff (1:20), while seroconvertion rates are defined as percentages. The significance lines represent the differences among the mean neutralization titers of the groups. It was considered p-values lower than 0.05 for the significance. One asterisk (*) = p-value < 0.05; two asterisks (**) = p-value < 0.01; and three asterisks (***) = p-value < 0.001.