Neutralization of Omicron sublineages and Deltacron SARS-CoV-2 by three doses of BNT162b2 vaccine or BA.1 infection

Abstract

Distinct SARS-CoV-2 Omicron sublineages have evolved showing increased fitness and immune evasion than the original Omicron variant BA.1. Here, we report the neutralization activity of sera from BNT162b2 vaccinated individuals or unimmunized Omicron BA.1-infected individuals against Omicron sublineages and "Deltacron" variant (XD). BNT162b2 post-dose 3 immune sera neutralized USA-WA1/2020, Omicron BA.1-, BA.2-, BA.2.12.1-, BA.3-, BA.4/5-, and XD-spike SARS-CoV-2s with geometric mean titres (GMTs) of 1335, 393, 298, 315, 216, 103, and 301, respectively; thus, BA.4/5 SARS-CoV-2 spike variant showed the highest propensity to evade vaccine neutralization compared to the original Omicron variants BA.1. BA.1-convalescent sera neutralized USA-WA1/2020, BA.1-, BA.2-, BA.2.12.1-, BA.3-, BA.4/5-, and Deltacron-spike SARS-CoV-2s with GMTs of 15, 430, 110, 109, 102, 25, and 284, respectively. The unique mutation F486V in the BA.4/5 spike contributes to the increased evasion of antibody neutralization by sublineage BA.4/5. The low neutralization titres of vaccinated sera or convalescent sera from BA.1 infected individuals against the emerging and rapidly spreading Omicron BA.4/5 variants provide important results for consideration in the selection of an updated vaccine in the current Omicron wave.Trial registration: ClinicalTrials.gov; identifier: NCT04368728.

Keywords: BNT162b2 vaccine; Omicron; SARS-CoV-2; neutralization; variants.

Figure 1.

Neutralization by sera collected at one-month post-dose 3 BNT162b2 vaccine (A) and by sera collected from unvaccinated individuals who contracted Omicron BA.1 SARS-CoV-2 (B). Scatterplot of neutralization titres against USA-WA1/2020, Omicron sublineage BA.1-, BA.2-, BA.2.12.1-, BA.3-, BA.4/5-, and Deltacron XD-spike mNG SARS-CoV-2s. Both BNT162b2-vaccinated sera (n = 22) and BA.1-infected convalescent sera (n = 20) were tested for their FFRNT₅₀s against the variant-spike mNG SARS-CoV-2s. The variant-spike mNG SARS-CoV-2s were produced by engineering the complete variant-spike genes into the mNG USA-WA1/2020. Each data point represents the geometric mean FFRNT50 (GMT) obtained with a serum specimen against the indicated virus. Tables S1 and S2 summa­rize the serum information and FFRNT₅₀s for (A) and (B), respectively. The neutralization titres for individual variant-spike mNG SARS-CoV-2s were determined in two or three independent experiments, each with duplicate assays; the GMTs are presented. The bar heights and the numbers above indicate GMTs. The whiskers indicate 95% confidence intervals. The dotted lines indicate the limit of detection of FFRNT₅₀. Statistical analysis was performed with the use of the Wilcoxon matched-pairs signed-rank test. For the BNT162b2-vaccinated sera in (A), the P-values of the GMT differences between USA-WA1/2020 and any variant-spike SARS-CoV-2 are all <.0001. For the BA.1-convelescent sera in (B), the P-value of GMT difference between BA.1- and XD-spike viruses is .0021; the P-values of the GMT differences between BA.1- and any other variant-spike viruses (including USA-WA1/2020) are all <.0001. For both serum panels in (A) and (B), FFRNT50 values with connected lines are presented for individual sera.