Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• COVID-19 (SARS-CoV-2) presents with varied severity, from asymptomatic to critical illness, involving immune dysregulation and cytokine storms.
• Previous coronavirus vaccine development faced challenges due to enhanced disease responses in animal models.
• Betacoronaviruses, including SARS-CoV-2, can infect phagocytic cells via antibody-bound Fc receptors, potentially leading to Antibody-Dependent Enhancement (ADE).

Purpose of the Study:

• To explore the potential role of Antibody-Dependent Enhancement (ADE) in COVID-19 and related inflammatory syndromes.
• To assess the implications of ADE for current and future SARS-CoV-2 therapeutics and vaccines.
• To highlight the importance of developing alternative vaccine strategies for SARS-CoV-2.

Main Methods:

• Review of existing literature on SARS-CoV-2 pathogenesis, immune responses, and vaccine development.
• Analysis of mechanisms by which SARS-CoV-2 antibodies might mediate ADE through Fc receptors on macrophages and mast cells.
• Examination of clinical observations, including multisystem inflammatory syndrome in children (MIS-C) and adults (MIS-A).

Main Results:

• Antibody-Dependent Enhancement (ADE) may contribute to increased COVID-19 severity, particularly with early high antibody levels.
• Maternally acquired SARS-CoV-2 antibodies bound to mast cells might be involved in MIS-C and MIS-A.
• Two distinct ADE mechanisms involving Fc receptors on macrophages and mast cells are proposed for SARS-CoV-2.

Conclusions:

• ADE poses risks for COVID-19 treatments, antibody therapies, convalescent plasma, and B-cell vaccines.
• Understanding ADE mechanisms is critical for designing safe and effective SARS-CoV-2 vaccines, especially for diverse populations.
• Developing SARS-CoV-2 T-cell vaccines, independent of antibody responses, is emphasized as a safer alternative.