Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• The Omicron (B.1.1.529) SARS-CoV-2 variant exhibits high transmissibility and immune escape.
• Vaccination provides protection against severe disease, likely mediated by cellular immunity.
• Understanding immune responses to Omicron in vaccinated individuals with prior infection history is crucial.

Purpose of the Study:

• To investigate T and B cell immunity against the Omicron variant (B.1.1.529) in triple-vaccinated healthcare workers.
• To assess the impact of different SARS-CoV-2 infection histories on immune responses to Omicron.
• To evaluate immune imprinting effects on cellular and antibody responses.

Main Methods:

• Analysis of T and B cell immunity against SARS-CoV-2 variants.
• Study population: triple BioNTech BNT162b2 mRNA-vaccinated healthcare workers (HCWs).
• Stratification based on infection history (naïve, prior variant infection, Wuhan Hu-1 infection).

Main Results:

• Triple vaccination boosted immunity against prior variants but showed reduced T and B cell responses to Omicron spike protein.
• Immune imprinting from Alpha (B.1.1.7) infection led to less durable binding antibodies against Omicron.
• Naïve HCWs infected during the Omicron wave had reduced neutralizing antibody potency and T cell responses against Omicron.

Conclusions:

• Omicron variant challenges pre-existing immunity from vaccination and prior infections.
• Prior infection history significantly modulates immune responses to SARS-CoV-2 variants, including Omicron.
• Immune imprinting can influence the durability and breadth of immune protection against evolving SARS-CoV-2 variants.