Heterologous Immunity Between SARS-CoV-2 and Pathogenic Bacteria

Area of Science:

• Immunology
• Infectious Diseases
• Molecular Biology

Background:

• Heterologous immunity, where T cells from one pathogen response recognize another, is proposed to influence COVID-19 severity variability.
• Understanding cross-reactivity between bacterial and viral pathogens is crucial for explaining diverse clinical outcomes.

Purpose of the Study:

• To investigate if bacterial peptide sensitization can induce heterologous immunity to SARS-CoV-2 peptides.
• To determine if SARS-CoV-2 vaccination can induce heterologous immunity to bacterial peptides.
• To explore the role of T cell cross-reactivity in COVID-19 severity.

Main Methods:

• In silico prediction identified 6 bacterial peptides with sequence homology to SARS-CoV-2 spike protein or NSP3.
• In vitro co-cultures assessed T cell responses (cytokine production, activation, proliferation) after bacterial peptide sensitization.
• Donor T cell responses were tracked before and after SARS-CoV-2 vaccination to measure cross-reactivity to bacterial peptides.

Main Results:

• All tested individuals (n=18) developed heterologous immunity to SARS-CoV-2 peptides upon sensitization with bacterial peptides.
• SARS-CoV-2 vaccination induced heterologous immunity to bacterial peptides.
• Identified T cell recall responses included IFN-γ, TNF, IL-2 production, CD69 activation, and CellTrace proliferation.

Conclusions:

• Bacterial peptides can induce heterologous T cell immunity to SARS-CoV-2, and SARS-CoV-2 vaccination can induce heterologous immunity to bacterial peptides.
• These findings provide a mechanism for T cell cross-reactivity between bacteria and SARS-CoV-2, potentially explaining COVID-19 severity variance.
• Demonstrated proof-of-concept for SARS-CoV-2 vaccination inducing heterologous immunity to bacterial peptides.