Potent human neutralizing antibodies elicited by SARS-CoV-2 infection

Abstract

The pandemic caused by emerging coronavirus SARS-CoV-2 presents a serious global public health emergency in urgent need of prophylactic and therapeutic interventions. SARS-CoV-2 cellular entry depends on binding between the viral Spike protein receptor-binding domain (RBD) and the angiotensin converting enzyme 2 (ACE2) target cell receptor. Here, we report on the isolation and characterization of 206 RBD-specific monoclonal antibodies (mAbs) derived from single B cells of eight SARS-CoV-2 infected individuals. These mAbs come from diverse families of antibody heavy and light chains without apparent enrichment for particular families in the repertoire. In samples from one patient selected for further analyses, we found coexistence of germline and germline divergent clones. Both clone types demonstrated impressive binding and neutralizing activity against pseudovirus and live SARS-CoV-2. However, the antibody neutralizing potency is determined by competition with ACE2 receptor for RBD binding. Surprisingly, none of the SARS-CoV-2 antibodies nor the infected plasma cross-reacted with RBDs from either SARS-CoV or MERS-CoV although substantial plasma cross-reactivity to the trimeric Spike proteins from SARS-CoV and MERS-CoV was found. These results suggest that antibody response to RBDs is viral species-specific while that cross-recognition target regions outside the RBD. The specificity and neutralizing characteristics of this plasma cross-reactivity requires further investigation. Nevertheless, the diverse and potent neutralizing antibodies identified here are promising candidates for prophylactic and therapeutic SARS-CoV-2 interventions.

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

“…We showed RBD-SpyVLPs to be strongly immunogenic in mice and pigs, inducing high titre neutralising antibody responses against wild type SARS-CoV-2 virus. This study confirms that the RBD is the key immunogenic domain for eliciting neutralising monoclonal antibodies against SARS-CoV-2, in line with studies showing that highly neutralising antibodies isolated from convalescent patients bind to the RBD 16,26,38,[40][41][42][43][44][45][46] . We showed that RBD-SpyVLPs are recognised by a panel of mAbs isolated from convalescent patients 26 binding to various epitopes on the RBD (Figure 2A).…”

Clinical sensitivity and interpretation of PCR and serological COVID‐19 diagnostics for patients presenting to the hospital

“…Plaque reduction neutralization tests are the gold standard for assessing neutralizing ability, [23][24][25][26] and ongoing studies are in progress to confirm anti-RBD antibodies are neutralizing in SARS-CoV-2 infection. 27 Some commercially available assays measure the more abundant nucleocapsid protein, which may increase sensitivity to detect a serologic response early in the course of infection, therefore, shifting the seroconversion curve to the left. However, antibodies to nucleocapsid protein are unlikely to provide protective immunity as nucleocapsid protein is inaccessible to antibodies in an intact virus.…”

Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants

“…Recent studies have shown that related, potently neutralizing monoclonal antibodies that recognize the SARS-CoV-2 receptor binding domain (RBD) are often elicited in SARS-CoV-2 infection (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). These antibodies have great potential to be clinically impactful in the treatment and prevention of SARS-CoV-2 infection.…”