Recombinant XBB.1.5 boosters induce robust neutralization against KP.2- and KP.3-included JN.1 sublineages

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Emerging SARS-CoV-2 variants, particularly JN.1 sublineages, exhibit significant immune evasion and neutralization resistance.
• Previous infection and vaccination histories influence humoral immune responses against evolving Omicron variants.

Purpose of the Study:

• To evaluate the neutralization capacity of serum samples from individuals with diverse infection and vaccination histories against Omicron variants.
• To assess the humoral immune response elicited by recombinant XBB vaccines against Omicron variants, including JN.1 sublineages (KP.2, KP.3).

Main Methods:

• Collected serum samples from adult participants with varied SARS-CoV-2 infection and vaccination backgrounds.
• Assessed neutralization activity against pseudoviruses of Omicron lineages using serum samples.
• Investigated immune responses to recombinant XBB vaccines and neutralization resistance of JN.1 sublineages.

Main Results:

• Sera from previous Omicron breakthrough infections showed limited neutralization against Omicron lineages.
• Boosters with WSK-V102C or WSK-V102D significantly elevated neutralizing antibody geometric mean titers (GMTs).
• WSK-V102D boosters 4 months post-vaccination demonstrated substantial GMTs against XBB.1.5, JN.1, and its sublineages, with notable increases compared to unvaccinated individuals.

Conclusions:

• Boosting with XBB.1.5 subunit vaccines induces robust antibody responses against JN.1 sublineages.
• JN.1 sublineages (KP.2, KP.3) display enhanced neutralization evasion compared to XBB.1.5.
• Updated vaccine boosters targeting JN.1, KP.2, or KP.3 may be necessary to counter increased immune evasion.