Bivalent mRNA vaccine booster enhances immunity against XBB.1.5 more effectively than breakthrough infection in...

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• SARS-CoV-2 Omicron subvariants, like XBB.1.5, exhibit immune evasion, impacting vaccine effectiveness.
• Continuous monitoring of vaccine-induced immunity against emerging variants is crucial.

Purpose of the Study:

• To evaluate immune responses and protection conferred by a bivalent mRNA vaccine against the SARS-CoV-2 XBB.1.5 variant.
• To compare homologous boosting with the bivalent vaccine versus breakthrough infection in mice.

Main Methods:

• K18-hACE2 mice received two or three doses of a bivalent mRNA vaccine (Wuhan-1/BA.4/5) or two doses followed by intranasal XBB.1.5 exposure.
• Immune responses, including neutralizing antibodies and cellular immunity, were assessed.
• Protection was evaluated by measuring viral load and lung inflammation post-challenge.

Main Results:

• Homologous boosting with the bivalent vaccine generated stronger neutralizing antibody and cellular immune responses against XBB.1.5 compared to breakthrough infection.
• Vaccination provided protection against severe disease, with boosting further enhancing protection by reducing lung viral RNA and inflammation.
• Intranasal XBB.1.5 exposure suggested immune memory reactivation, though productive infection was not confirmed.

Conclusions:

• Homologous boosting with the bivalent mRNA vaccine enhances cross-variant immunity and protection against the SARS-CoV-2 XBB.1.5 variant in a naive mouse model.
• Updated vaccines are valuable for broadening immune responses and improving protection against evolving SARS-CoV-2 variants.