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Neutralizing antibody response to XBB.1.5, BA.2.86, FL.1.5.1 and JN.1 six months after the BNT162b2 bivalent booster.

INTRODUCTION: An increase evasion of the SARS-CoV-2 virus towards vaccination strategies and natural immunity has been rapidly described notably due to mutations in the spike receptor binding domain and the N-terminal domain.

MATERIAL AND METHODS: Participants of the CRO-VAX HCP study who received the bivalent booster were followed at 6 months. A pseudovirus-neutralization test was used to assess the neutralization potency of antibodies against D614G, Delta, BA.1, BA.5, XBB.1.5, BA.2.86, FL.1.5.1, and JN-1.

RESULTS: The neutralizing capacity of antibodies against Omicron variant or subvariants was significantly reduced compared to D614G and Delta (p<0.0001). The lowest neutralizing response that was observed with JN-1 (GMT=22.1) was also significantly lower compared to XBB.1.5 (GMT=29.5, p<0.0001), BA.2.86 (GMT=29.6, p<0.0001), and FL.1.5.1 (GMT=25.2, p<0.0001). Participants that contracted a breakthrough infection due to XBB.1.5 had significantly higher neutralizing antibodies against all variants compared to uninfected participants, especially against Omicron variant and subvariants.

CONCLUSION: Our results confirm that JN.1 is one of the most immune evading variants to date and that the BA.2.86 subvariant did not show an increased immunity escape compared to XBB.1.5. The stronger response in BKI with Omicron variant and subvariants supports the need to use vaccine antigens that target circulating variants.

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