Humoral Responses against BQ.1.1 Elicited after Breakthrough Infection and SARS-CoV-2 mRNA Vaccination

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• The Omicron BQ.1.1 variant, with numerous Spike glycoprotein mutations, exhibits resistance to immune responses from monovalent mRNA vaccines.
• Bivalent mRNA vaccines have been approved to enhance immune responses against Omicron subvariants.

Purpose of the Study:

• To assess the effectiveness of plasma from individuals vaccinated with a fourth dose of mRNA vaccine (mono- or bivalent) in recognizing and neutralizing ancestral (D614G) and BQ.1.1 SARS-CoV-2 Spike proteins.
• To compare immune responses in vaccinated individuals with and without recent SARS-CoV-2 infection.

Main Methods:

• Plasma samples were collected from vaccinated individuals before and after a fourth mRNA vaccine dose.
• The capacity of plasma to recognize and neutralize ancestral (D614G) and BQ.1.1 Spike proteins was measured.

Main Results:

• Individuals showed significantly better recognition and neutralization of the ancestral Spike compared to BQ.1.1, both before and after the fourth vaccine dose.
• Fourth-dose vaccinated individuals with recent SARS-CoV-2 infection demonstrated superior recognition and neutralization of the BQ.1.1 Spike compared to those without recent infection or with older infections.
• This enhanced response was independent of the specific mRNA vaccine used.

Conclusions:

• Hybrid immunity, resulting from vaccination combined with recent infection, elicits stronger humoral responses against SARS-CoV-2 variants like BQ.1.1 than vaccination alone.
• Recent infection plays a crucial role in broadening and strengthening immune responses to circulating SARS-CoV-2 variants, irrespective of the mRNA vaccine platform.