Acute B Cell and Antibody Responses
The humoral immune response is critical for the clearance of cytopathic viruses and is a major part of the memory response that prevents reinfection. SARS-CoV-2 elicits a robust B cell response, as evidenced by the rapid and near-universal detection of virus-specific IgM, IgG and IgA, and neutralizing IgG antibodies (nAbs) in the days following infection. The kinetics of the antibody response to SARS-CoV-2 are now reasonably well described (Huang et al., 2020a).
Similar to SARS-CoV-1 infection (Hsueh et al., 2004), seroconversion occurs in most COVID-19 patients between 7 and 14 days after the onset of symptoms, and antibody titers persist in the weeks following virus clearance (Figure 4 ) (Haveri et al., 2020, Lou et al., 2020, Okba et al., 2020, Tan et al., 2020b, Wölfel et al., 2020, Wu et al., 2020b, Zhao et al., 2020a). Antibodies binding the SARS-CoV-2 internal N protein and the external S glycoprotein are commonly detected (Amanat et al., 2020, Ju et al., 2020, To et al., 2020). The receptor binding domain (RBD) of the S protein is highly immunogenic, and antibodies binding this domain can be potently neutralizing, blocking virus interactions with the host entry receptor, ACE2 (Ju et al., 2020, Wu et al., 2020b). Anti-RBD nAbs are detected in most tested patients (Ju et al., 2020, To et al., 2020, Wu et al., 2020b). Although crossreactivity to SARS-CoV-1 S and N proteins and to MERS-CoV S protein was detected in plasma from COVID-19 patients, no crossreactivity was found to the RBD from SARS-CoV-1 or MERS-CoV. In addition, plasma from COVID-19 patients did not neutralize SARS-CoV-1 or MERS-CoV (Ju et al., 2020).
Figure 4 Antibody-Mediated Immunity in SARS-CoV-2
Virus-specific IgM and IgG are detectable in serum between 7 and 14 days after the onset of symptoms. Viral RNA is inversely correlated with neutralizing antibody titers. Higher titers have been observed in critically ill patients, but it is unknown whether antibody responses somehow contribute to pulmonary pathology. The SARS-CoV-1 humoral response is relatively short lived, and memory B cells may disappear altogether, suggesting that immunity with SARS-CoV-2 may wane 1–2 years after primary infection.
RBD-specific CD19+IgG+ memory B cells were single-cell sorted from a cohort of eight COVID-19 donors between days 9 and 28 after the onset of symptoms (Ju et al., 2020). From their antibody gene sequences, 209 SARS-CoV-2-specific monoclonal antibodies were produced. The monoclonal antibodies had a diverse repertoire, relatively low or no somatic mutations, and variable binding reactivity, with dissociation constants reaching 10−8 to 10−9, similar to antibodies isolated during acute infections. Two potent neutralizing SARS-CoV-2 RBD-specific monoclonal antibodies were characterized that did not crossreact with the RBD of SARS-CoV-1 or MERS-CoV (Ju et al., 2020). Together, these results demonstrate that antibody mediated neutralization is virus specific and likely driven by binding of epitopes within the RBD.