SARS-CoV-2 and SARS-CoV share 79.6% sequence identity, use the same input receptor (ACE2), and cause similar acute respiratory syndromes. As such, key insights from studies of the immune response to SARS-CoV should be considered when developing vaccines for SARS-CoV-2. Crucially, although antibody titers are generally used as protective correlates, high antibody titers and early seroconversion are reported to correlate with disease severity in SARS1 patients.
The quality and quantity of the antibody response dictate the functional results. High-affinity antibodies can cause neutralization by recognizing specific viral epitopes (Figure 1a). Neutralizing antibodies are defined in vitro by their ability to block viral entry, fusion, or exit. In vivo, neutralizing antibodies can function without additional mediators, although the Fc region is necessary for the neutralization of the influenza2 virus.
In the case of SARS-CoV, viral coupling to ACE2 in host cells is blocked when neutralizing antibodies, for example, recognizing the receptor-binding domain (RBD) on peak (S) 3 protein. Protein S-mediated viral fusion can be blocked by neutralizing antibodies that target the heptad repeat 2 domain (HR2).
Additionally, neutralizing antibodies can interact with other immune components, including complement, phagocytes, and natural killer cells. These effector responses can aid in pathogen clearance, and phagocyte involvement has been shown to enhance antibody-mediated SARS-CoV4. However, in rare cases, pathogen-specific antibodies can promote pathology, resulting in a phenomenon known as antibody-dependent enhancement (ADE).