Previous exposure to Spike-providing parental strains confers neutralizing immunity to XBB lineage and other SARS-CoV-2 recombinants in the context of vaccination

Abstract

The emergence of SARS-CoV-2 recombinants is of particular concern as they can result in a sudden increase in immune evasion due to antigenic shift. Recent recombinants XBB and XBB.1.5 have higher transmissibility than previous recombinants such as "Deltacron." We hypothesized that immunity to a SARS-CoV-2 recombinant depends on prior exposure to its parental strains. To test this hypothesis, we examined whether Delta or Omicron (BA.1 or BA.2) immunity conferred through infection, vaccination, or breakthrough infection could neutralize Deltacron and XBB/XBB.1.5 recombinants. We found that Delta, BA.1, or BA.2 breakthrough infections provided better immune protection against Deltacron and its parental strains than did the vaccine booster. None of the sera were effective at neutralizing the XBB lineage or its parent BA.2.75.2, except for the sera from the BA.2 breakthrough group. These results support our hypothesis. In turn, our findings underscore the importance of multivalent vaccines that correspond to the antigenic profile of circulating variants of concern and of variant-specific diagnostics that may guide public health and individual decisions in response to emerging SARS-CoV-2 recombinants.

Keywords: SARS-CoV-2; humoral immunity; neutralization; recombinants; vaccine.

Figure 1.

Vaccine-induced and hybrid immunity effectively neutralizes Deltacron variants but not XBB lineage. (A–E). Scatter dot plots of neutralizing-antibody titres against Omicron-Delta spike (o/δ-spike), Delta-Omicron spike (δ/ο-spike), XBB, XBB.1.5 and BA.2.75.2 variants by sera from: two-doses mRNA-vaccinated individuals (n = 10); vaccinated and boosted (three doses of mRNA vaccine) individuals (n = 10); unvaccinated individuals infected with Delta (n = 11), BA.1(n = 8); BA.2 (n = 9); vaccinated or boosted individuals with breakthrough infections by Delta (n = 5), BA.1 (n = 11), and (H) BA.2 (n = 23). In all cases, geometric mean values for the 50% neutralization titres (NT50) are provided at the top of the plots. Each dot represents an individual serum sample. Statistical significance was analyzed by unpaired ordinary one-way ANOVA with Tukey’s multiple comparison test (*P < 0.05, **p < 0.001,**** p < 0.0001). The details regarding samples (group, age, sex, COVID-19 infection status, severity, vaccination dates, and sample collection dates after infection or symptoms are summarized in supplementary data Table 1).