The potential danger of suboptimal antibody responses in COVID-19

Abstract

There is a desperate need for effective therapies and vaccines for SARS-CoV-2 to mitigate the growing economic crisis that has ensued from societal lockdown. Vaccines are being developed at an unprecedented speed and are already in clinical trials, without preclinical testing for safety and efficacy. Yet, safety evaluation of candidate vaccines must not be overlooked.

Fig. 1. Potential outcomes of antibody response to coronavirus.

a | In antibody-mediated viral neutralization, neutralizing antibodies binding to the receptor-binding domain (RBD) of the viral spike protein, as well as other domains, prevent virus from docking onto its entry receptor, ACE2. b | In antibody-dependent enhancement of infection, low quality, low quantity, non-neutralizing antibodies bind to virus particles through the Fab domains. Fc receptors (FcRs) expressed on monocytes or macrophages bind to Fc domains of antibodies and facilitate viral entry and infection. c | In antibody-mediated immune enhancement, low quality, low quantity, non-neutralizing antibodies bind to virus particles. Upon engagement by the Fc domains on antibodies, activating FcRs with ITAMs initiate signalling to upregulate pro-inflammatory cytokines and downregulate anti-inflammatory cytokines. Immune complexes and viral RNA in the endosomes can signal through Toll-like receptor 3 (TLR3), TLR7 and/or TLR8 to activate host cells, resulting in immunopathology.