The SARS-CoV-2 antibody-dependent enhancement façade

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Antibody-dependent enhancement (ADE) describes how prior infection can worsen subsequent infections.
• This phenomenon is well-documented in dengue virus infections.
• Speculation exists regarding ADE in SARS-CoV-2 due to coronavirus antibody-mediated entry, but evidence is lacking.

Purpose of the Study:

• To investigate the potential for antibody-dependent enhancement (ADE) of SARS-CoV-2.
• To evaluate the in vivo and epidemiological evidence for ADE in SARS-CoV-2 infections.
• To analyze the mechanisms of SARS-CoV-2 entry mediated by antibodies.

Main Methods:

• Review of existing in vivo and epidemiological data on SARS-CoV-2.
• Analysis of demonstrated antibody-dependent SARS-CoV-2 entry mechanisms (FcR-dependent, ACE2-FcR-interdependent, FcR-independent).
• Examination of antibody specificity's role in viral entry pathways.

Main Results:

• Three distinct antibody-dependent SARS-CoV-2 entry mechanisms have been identified.
• Antibody targeting of the receptor binding domain (RBD) or N-terminal domain influences entry pathways.
• Robust evidence demonstrating ADE of SARS-CoV-2 or contribution to severe disease is currently absent.

Conclusions:

• While antibody-dependent entry mechanisms for SARS-CoV-2 exist, they have not been definitively linked to enhanced infection or ADE.
• Antigenic imprinting leading to ADE in SARS-CoV-2 remains a theoretical concern without supporting evidence.
• Current data do not support the phenomenon of antibody-dependent enhancement in SARS-CoV-2 infections.