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.