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.

Bivalent COVID-19 vaccines boost the capacity of pre-existing SARS-CoV-2-specific memory B cells to cross-recognize Omicron subvariants

“…However, we found that four-weeks post-dose four the BA.1 and BA.5 bivalent vaccines boosted the ability of WH1 RBD-specific Bmem to bind antigenically distinct subvariants including those not contained in the bivalent vaccines, BQ.1.1 and XBB.1.5. This expands on previous analyses of NAb, which showed improved recognition of XBB and other related subvariants following the BA.5 bivalent mRNA vaccine or an Omicron BTI (14,15,39,49). Therefore, we reveal novel evidence that cross-reactive Bmem binding both WH1 and Omicron subvariants are boosted by a bivalent fourth dose.…”

Regulation of virion production by the ORF8 signal peptide across SARS-CoV-2 variants

“…Rep-WT, Rep-ORF8-stop, icXBB.1.5, and icXBB.1.5+ORF8 were generated following pGLUE method in the pBAC SARS-CoV-2 construct as previously described (22). Briefly, the SARS-CoV-2 genome was divided into 10 fragments, which were cloned and later ligated via BsaI digestion and Golden Gate assembly protocol as described by Taha et al (22,37). The ligated plasmid was confirmed via nanopore sequencing (Primordium Labs).…”