Initial antigen encounter determines robust T-cell immunity against SARS-CoV-2 BA.2.86 variant three years later

Area of Science:

• Immunology
• Virology
• Genetics

Background:

• The emergence of hypermutated SARS-CoV-2 variants like BA.2.86 poses challenges to existing immunity.
• Understanding adaptive immune responses, particularly T-cell immunity, is crucial for predicting variant impact and informing control strategies.

Purpose of the Study:

• To evaluate the cross-recognition of the SARS-CoV-2 BA.2.86 variant by adaptive immune responses.
• To identify factors influencing T-cell cross-recognition, including viral genetic determinants and prior exposure history.

Main Methods:

• Measurement of BA.2.86 neutralizing antibodies and T-cell responses cross-reactivity in previously exposed individuals.
• Investigation of clinical-demographic factors associated with immune responses.
• In silico analysis to assess viral genetic determinants impacting T-cell responses.

Main Results:

• While neutralizing antibodies showed notable escape from BA.2.86, T-cell responses remained generally preserved.
• A small but significant average loss in T-cell cross-recognition (7.5-10.8%) was observed, linked to BA.2.86 mutations affecting T-cell epitopes.
• T-cell responses were significantly higher when initially induced by infection compared to vaccination, and increased with the number of infections.

Conclusions:

• T-cell immunity plays a critical role in recognizing evolving SARS-CoV-2 variants.
• The initial antigen encounter (infection vs. vaccination) and cumulative infection history are key factors influencing the magnitude and breadth of T-cell responses.
• These insights are vital for developing effective strategies to control SARS-CoV-2 spread amidst viral evolution.