Potent Anti-SARS-CoV-2 Efficacy of COVID-19 Hyperimmune Globulin from Vaccine-Immunized Plasma.

Coronavirus disease 2019 (COVID-19) remains a global public health threat. Hence, more effective and specific antivirals are urgently needed. Here, COVID-19 hyperimmune globulin (COVID-HIG), a passive immunotherapy, is prepared from the plasma of healthy donors vaccinated with BBIBP-CorV (Sinopharm COVID-19 vaccine). COVID-HIG shows high-affinity binding to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, the receptor-binding domain (RBD), the N-terminal domain of the S protein, and the nucleocapsid protein; and blocks RBD binding to human angiotensin-converting enzyme 2 (hACE2). Pseudotyped and authentic virus-based assays show that COVID-HIG displays broad-spectrum neutralization effects on a wide variety of SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in vitro. However, a significant reduction in the neutralization titer is detected against Beta, Delta, and Omicron variants. Additionally, assessments of the prophylactic and treatment efficacy of COVID-HIG in an Adv5-hACE2-transduced IFNAR-/- mouse model of SARS-CoV-2 infection show significantly reduced weight loss, lung viral loads, and lung pathological injury. Moreover, COVID-HIG exhibits neutralization potency similar to that of anti-SARS-CoV-2 hyperimmune globulin from pooled convalescent plasma. Overall, the results demonstrate the potential of COVID-HIG against SARS-CoV-2 infection and provide reference for subsequent clinical trials.

Yu D ，Li YF ，Liang H ，Wu JZ ，Hu Y ，Peng Y ，Li TJ ，Hou JF ，Huang WJ ，Guan LD ，Han R ，Xing YT ，Zhang Y ，Liu J ，Feng L ，Li CY ，Liang XL ，Ding YL ，Zhou ZJ ，Ji DM ，Wang FF ，Yu JH ，Deng K ，Xia DM ，Dong DM ，Hu HR ，Liu YJ ，Fu DX ，He YL ，Zhou DB ，Yang HC ，Jia R ，Ke CW ，Du T ，Xie Y ，Zhou R ，Li CS ，Wang ML ，Yang XM ... -  《Advanced Science》

Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Hyperimmune Immunoglobulin Demonstrates Potent Neutralization and Antibody-Dependent Cellular Cytotoxicity and Phagocytosis Through N and S Proteins.

Although coronavirus disease 2019 (COVID-19) vaccinations have provided a significant reduction in infections, effective COVID-19 treatments remain an urgent need. Functional characterization of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hyperimmune immunoglobulin (hIG) from human convalescent plasma was performed by different virus neutralization methodologies (plaque reduction, virus-induced cytotoxicity, median tissue culture infectious dose [TCID50] reduction, and immunofluorimetry) at different laboratories using geographically different SARS-CoV-2 isolates (USA [1], Italy [1], and Spain [2]; 2 containing the D614G mutation). Neutralization capacity against the original Wuhan SARS-CoV-2 strain and variants (D614G mutant, B.1.1.7, P.1, and B.1.351) was evaluated using a pseudovirus expressing the corresponding spike (S) protein. Antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) was also evaluated. All SARS-CoV-2 isolates were potently neutralized by hIG as shown by all 4 methodologies. Wild-type SARS-CoV-2 and variants were effectively neutralized using the pseudovirus. The hIG (IgG type) induced ADCC and ADCP against SARS-CoV-2 N and S proteins but not E protein. Very low concentrations (25-100 µg IgG/mL) were required. A potent effect was triggered by antibodies in hIG solutions against the SARS-CoV-2 S and N proteins. Beyond neutralization, IgG Fc-dependent pathways may play a role in combatting SARS-CoV-2 infections using COVID-19 hIG. This could be especially relevant for the treatment of more neutralization-resistant SARS-CoV-2 variants.

Díez JM ，Romero C ，Cruz M ，Vandeberg P ，Merritt WK ，Pradenas E ，Trinité B ，Blanco J ，Clotet B ，Willis T ，Gajardo R ... -  《-》

Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain.

Yang M ，Li J ，Huang Z ，Li H ，Wang Y ，Wang X ，Kang S ，Huang X ，Wu C ，Liu T ，Jia Z ，Liang J ，Yuan X ，He S ，Chen X ，Zhou Z ，Chen Q ，Liu S ，Li J ，Zheng H ，Liu X ，Li K ，Yao X ，Lang B ，Liu L ，Liao HX ，Chen S ... -  《Microbiology Spectrum》

A Glycosylated RBD Protein Induces Enhanced Neutralizing Antibodies against Omicron and Other Variants with Improved Protection against SARS-CoV-2 Infection.

Shi J ，Zheng J ，Tai W ，Verma AK ，Zhang X ，Geng Q ，Wang G ，Guan X ，Malisheni MM ，Odle AE ，Zhang W ，Li F ，Perlman S ，Du L ... -  《-》

Characterization of SARS-CoV-2 Variants B.1.617.1 (Kappa), B.1.617.2 (Delta), and B.1.618 by Cell Entry and Immune Evasion.

Ren W ，Ju X ，Gong M ，Lan J ，Yu Y ，Long Q ，Kenney DJ ，O'Connell AK ，Zhang Y ，Zhong J ，Zhong G ，Douam F ，Wang X ，Huang A ，Zhang R ，Ding Q ... -  《mBio》