4.4 Neutralizing antibody
The neutralizing antibody-mediated humoral response is a decisive role in prevention of viral infections. The neutralizing antibodies (NAbs) induced by vaccines or infected virus will bind to the surface epitopes of viral particles, and thus can reduce viral infectivity. In this way, they block entry of the virus into an infected cell (Klasse, 2014). Given the high affinity of the S protein for human ACE2 which explains the high rate of human-to-human transmission, the S protein is a potential target for antibody-mediated neutralization. It was reported that RBD within S1 unit is the most critical target for SARS-CoV Nabs (Wong, Li, Moore, Choe, & Farzan, 2004). There is evidence that RBD region can be recognized by most of Nabs (Coughlin et al., 2007; Duan et al., 2005; Greenough et al., 2005; Sui et al., 2004; ter Meulen et al., 2006; van den Brink et al., 2005; Z. Zhu et al., 2007). In a previous study, specific antibodies against SARS-CoV, such as, 80R (Sui et al., 2004), CR3014 (van den Brink et al., 2005), CR3022 (ter Meulen et al., 2006), and m396 (Z. Zhu et al., 2007), were identified by phage from both naïve and immune antibody libraries, which led to the blockage of the binding of S1 domain and ACE2. In addition, 80R, CR3013, and m396 showed virus neutralization and prophylaxis capability in vitroor animal models (ter Meulen et al., 2006). Two NAbs, 201 and 68 which are effective for virus prophylaxis in animal models, were identified in transgenic mice transgenic mice carrying human immunoglobulin genes. The mice have been used for producing NAbs against SARS-CoV via antigen immunization (Coughlin et al., 2007; Greenough et al., 2005).
The fasted and simple method of combating SARS-CoV-2 is the use of convalescent plasma mentioned above, which can induce polyclonal Nabs (Cheng et al., 2005), but SARS-CoV-2-specific neutralizing monoclonal antibodies have also been reported. These neutralizing antibodies can effectively treat COVID-19 (P. Zhou et al., 2020). However, it been observed that SARS-CoV NAbs do not effectively bind to SARS-CoV-2 S protein (X. Tian et al., 2020; Wrapp et al., 2020). As showed in a study, a SARS-CoV antibody, CR3022, bound to SARS-CoV-2 RBD with high affinity, but its neutralization capability is unkown (X. Tian et al., 2020). There is another study recording that SARS-CoV RBD-specific polyclonal antibodies and SARS-CoV-2 infection in HEK293T cells neutralized each other, stably expressing the human ACE2 receptor, hence it can be used to develop SARS-CoV RBD-based vaccines that might eventually prevent SARS-CoV-2 and SARS-CoV infection (Tai et al., 2020). In the treatment of Ebola and SARS viruses, a mix of NAbs showed stronger neutralization capability than onefold NAbs (Davey et al., 2016; ter Meulen et al., 2006). Therefore, by using the mixture of several potent Nabs, escape virus is less likely to be isolated with decreased sensitivity to neutralization. Since there are no SARS-CoV-2-specific vaccines and antibodies, it is also possible that a single use or combination of SARS-CoV RBD-targeting NAbs might provide prophylaxis and treatment benefits against SARS-CoV-2 infection.