Enhanced neutralization of SARS-CoV-2 XBB sub-lineages and BA.2.86 by a tetravalent COVID-19 vaccine booster

Abstract

As the SARS-CoV-2 virus continues to evolve, novel XBB sub-lineages such as XBB.1.5, XBB.1.16, EG.5, HK.3 (FLip), and XBB.2.3, as well as the most recent BA.2.86, have been identified and aroused global concern. Understanding the efficacy of current vaccines and the immune system's response to these emerging variants is critical for global public health. In this study, we evaluated the neutralization activities of sera from participants who received COVID-19 inactivated vaccines, or a booster vaccination of the recently approved tetravalent protein vaccine in China (SCTV01E), or had contracted a breakthrough infection with BA.5/BF.7/XBB virus. Comparative analysis of their neutralization profiles against a broad panel of 30 SARS-CoV-2 sub-lineage viruses revealed that strains such as BQ.1.1, CH.1.1, and all the XBB sub-lineages exhibited heightened resistance to neutralization than previous variants, however, despite the extra mutations carried by emerging XBB sub-lineages and BA.2.86, they did not demonstrate significantly increased resistance to neutralization compared to XBB.1.5. Encouragingly, the SCTV01E booster vaccination consistently induced robust and considerably higher neutralizing titers against all these variants than breakthrough infection did. Cellular immunity assays also showed that the SCTV01E booster vaccination elicited a higher frequency of virus-specific memory B cells but not IFN-γ secreting T cells. Our findings underline the importance of developing novel multivalent vaccines to more effectively combat future viral variants.

Evaluation of the cross reactivity of neutralising antibody response in vaccinated human and convalescent hamster sera against SARS-CoV-2 variants up to and including JN.1 using an authentic virus neutralisation assay

“…All variants tested displayed increased resistance to neutralisation to this four-dose panel relative to both ancestral and BA.4, with similar GM titres for all except JN.1 (CH.1.1, BQ.1.22, XBB.1.1, XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1.1, BA.2.86). This aligns with results presented by other groups using both pseudovirus (PSV) and authentic virus assays against panels of vaccinated (three- and four-dose) with additional break-through infection in a globally diverse population [45–52]. It is also of interest that the GM titres, up to and including BA.2.86, are comparable despite the genetic diversity in the variants tested against our four-dose panels.…”

“…with additional break-through infection in a globally diverse population [45][46][47][48][49][50][51][52]. It is also of interest that the GM titres, up to and including BA.2.86, are comparable despite the genetic diversity in the variants tested against our four-dose panels.…”

Preclinical Characterization of the Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine

“…BA.2.86 remains designated as a variant under monitoring (VUM) by the World Health Organization due to the substantial amino acid changes in its S protein (34). However, no sublineage from the BA.2.86 cluster has been reported to cause an increase in COVID-19 disease severity or deaths (35)(36)(37)(38)(39)(40)(41).…”

SARS-CoV-2 BA.2.86 (“Pirola”): Is it Pi or Just Another Omicron Sublineage?

“…Data on the capacity of breakthrough-infected (BTI) subjects to neutralize BA.2.86 have been reported by multiple groups. In general, either BA.2 BT alone [4], BF.7/BA.5 BTI alone [10][11][12], or XBB BTI alone [4][5][6]8,10,11] were not enough to elicit protective titers, but BA.5/BF.7+XBB BTI [5] or (monovalent or bivalent) vaccination plus BA.1/BA.4/BA.5 BTI [9] or XBB.1.5 BTI [13] raised titers, in line with the heterologous immunity theory formerly validated for COVID-19-convalescent plasma [14,15]. Regardless of vaccine status, pre-Omicron [9], BA.1 [9], or pre-XBB [16] BTI sera neutralized poorly, but contemporary sera instead had high titers [16].…”

“…Immune escape from vaccine-elicited neutralizing antibodies has been investigated in small cohorts (about 20 per group) of recipients of monovalent mRNA vaccines (three [6,8] or four doses [8]), wt+BA.1 bivalent mRNA vaccines [8], wt+BA.5 bivalent mRNA vaccines [4,6,8,10,17], the tetravalent subunit vaccine SCTV01E [11], and the inactivated protein subunit vaccine ZF2001 or ZF2202-A [12]. All of these studies were run with pseudoviruses, except for two on wt+BA.5 which employed live authentic BA.2.86 [10,13].…”