Omicron Sub-Lineage BA.5 and Recombinant XBB Evasion from Antibody Neutralisation in BNT162b2 Vaccine Recipients

Abstract

The recent emergence of a number of new SARS-CoV-2 variants resulting from recombination between two distinct parental lineages or sub-lineages within the same lineage has sparked the debate regarding potential enhanced viral infectivity and immune escape. Among these, XBB, recombinant of BA.2.10 and BA.2.75, has caused major concern in some countries due to its rapid increase in prevalence. In this study, we tested XBB escape capacity from mRNA-vaccine-induced (BNT162b2) neutralising antibodies compared to B.1 ancestral lineage and another co-circulating variant (B.1.1.529 BA.5) by analysing sera collected 30 days after the second dose in 92 healthcare workers. Our data highlighted an enhanced and statistically significant immune escape ability of the XBB recombinant. Although these are preliminary results, this study highlights the importance of immune escape monitoring of new and forthcoming variants and of the reformulation of existing vaccines.

Keywords: SARS-CoV-2; XBB recombinant; immune escape; mRNA-vaccine; neutralising antibody response.

Figure 1

Comparison of neutralising antibody titres of low (titres 20 and 40) and medium (titres 80 and 160) neutralising sera against SARS-CoV-2 original strain B.1, lineage B.1.1.529 BA.5 and recombinant XBB at four weeks after the second dose of BNT162b2 vaccine. Sera were grouped depending on the neutralisation titre against ancestral lineage B.1 and retested with lineage BA.5 and recombinant XBB. For each group, 12 sera were tested (n = 12). Results for sera with a neutralisation titre of 20, 40, 80 and 160 are shown in panels (A), (B), (C) and (D), respectively. Neutralisation titre is expressed as the reciprocal of the highest serum dilution capable of inhibiting the appearance of a visible cytopathic effect. The detection limit of the assay is defined as a titre of 10; sera which did not reach the detection limit were considered negative and their titre was approximated to zero. The upper limit of detection is defined as a titre of 5120. Statistical comparison of neutralisation titres against the three considered viral variants were compared using a one-way repeated-measures ANOVA test (*** p < 0.01, ns = not significant). Medians are indicated with solid horizontal lines, means with dashed horizontal lines and standard deviations with dashed oblique lines.

Figure 2

Comparison of neutralising antibody titres of highly neutralising sera (titres 320, 640, 1280 and 2560) against SARS-CoV-2 original strain B.1, lineage B.1.1.529 BA.5 and recombinant XBB at four weeks after the second dose of BNT162b2 vaccine. For the groups of sera with titres of 320, 640 and 1280, a total of 12 samples were tested (n = 12), while for the group of sera with a titre of 2560, only 8 samples were included (n = 8). Results for sera with a neutralisation titre of 320, 640, 1280 and 2560 are shown in panels (A), (B), (C) and (D), respectively. The detection limit of the assay is defined as a titre of 10; sera which did not reach the detection limit were considered negative and their titre was approximated to zero. The upper limit of detection is defined as a titre of 5120. Statistical comparison of neutralisation titres against the three considered viral variants were compared using a one-way repeated-measures ANOVA test (*** p < 0.01, ** p < 0.05). Medians are indicated with solid horizontal lines, means with dashed horizontal lines and standard deviations with dashed oblique lines.

Figure 3

Correlation between anti-S1/S2 IgG values and neutralisation titres against ancestral strain B.1 and mutated lineage B.1.1.529 BA.5 and recombinant XBB, separately, as shown in panels (A), (B) and (C), respectively. Correlation between neutralising titre against lineage B.1 and both mutated variants was also analysed (panel (D) for B.1-BA.5 correlation and panel (E) for B.1-XBB correlation). Statistical correlation was tested using a non-parametric two-tailed Spearman’s rank correlation. Results r values and p values are reported in each graph (*** p < 0.01, ** p < 0.05).

Figure 3

Correlation between anti-S1/S2 IgG values and neutralisation titres against ancestral strain B.1 and mutated lineage B.1.1.529 BA.5 and recombinant XBB, separately, as shown in panels (A), (B) and (C), respectively. Correlation between neutralising titre against lineage B.1 and both mutated variants was also analysed (panel (D) for B.1-BA.5 correlation and panel (E) for B.1-XBB correlation). Statistical correlation was tested using a non-parametric two-tailed Spearman’s rank correlation. Results r values and p values are reported in each graph (*** p < 0.01, ** p < 0.05).