SARS-CoV-2 Beta and Delta variants trigger Fc effector function with increased cross-reactivity

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs) can escape neutralizing antibodies, impacting vaccine effectiveness.
• Fc effector functions of antibodies are crucial for disease outcome and vaccine protection but their evasion by VOCs is not well understood.

Purpose of the Study:

• To investigate if SARS-CoV-2 VOCs trigger Fc effector functions with altered specificity.
• To determine the impact of VOCs on Fc effector function escape and cross-reactivity.

Main Methods:

• Assessing Fc effector activity evasion by the Beta VOC in individuals infected with the original SARS-CoV-2 (D614G) variant.
• Comparing Fc cross-reactivity against global VOCs triggered by Beta and Delta infections versus D614G infection or Ad26.COV2.S vaccination.

Main Results:

• The Beta VOC partially evades Fc effector activity, with differential impact across various functions.
• Beta and Delta infections induce Fc responses with enhanced cross-reactivity against global VOCs compared to D614G infection or vaccination.
• The infecting spike sequence influences Fc effector function, similar to neutralization.

Conclusions:

• SARS-CoV-2 VOCs can partially escape antibody-mediated Fc effector functions.
• Infections with specific VOCs like Beta and Delta can broaden Fc effector responses against other VOCs.
• Vaccine strategies incorporating VOCs may enhance Fc effector responses, potentially improving protection.