Antibodies can be designed to bind to specific antigens such as cells, proteins, peptides, or small molecules. Due to their specificity and binding affinity, these immunoglobulins can serve multiple purposes such as therapy, research, and diagnostics.
Depending on the type of antigen they target, therapeutic antibodies can elicit dramatically different responses such as neutralization, opsonization, complement-dependent cytotoxicity (CDC), or antibody-dependent cell-mediated cytotoxicity (ADCC). In the case of the COVID-19 disease, the major target for the development of neutralizing antibodies is the spike glycoprotein of SARS-CoV-2. Anti-spike antibodies with high affinity and specificity towards this protein could potentially neutralize the infection before membrane fusion and viral internalization can take place. Antibody opsonization, on the contrary, occurs when these molecules are designed to enhance the phagocytosis of the viral particles by macrophages and dendritic cells.
CDC and ADCC-activating antibodies elicit more complex and often undesirable responses. For instance, previous studies with SARS-CoV, the causative agent of the 2003 pandemic, showed that this virus could lead to the production of antibodies with suboptimal affinity thus causing complement activation and subsequent inflammation and fibrosis. The ADCC mechanism works by activating effector cells containing Fc receptors, this response has also been linked to pulmonary inflammation and lung injury. For this reason, molecules that block FcR activation such as intravenous immunoglobulin (IVIG) prepared from human serum, represent an attractive alternative for the treatment of the COVID-19 pathology.
Antibodies for diagnostics can be designed to target high-abundance markers such as SARS-CoV-2 nucleoprotein. While antibodies for research can be designed to target any of the
structural and nonstructural proteins of this new strain of coronavirus. There are still considerable gaps in knowledge regarding SARS-CoV-2 mechanism of action, for this reason, even nonstructural conserved proteins can be tested to increase our understanding of this virus and the COVID-19 pathology.
