COVID-19 pandemic is a global public health emergency. Despite extensive research, there are still few effective treatment options available today. Neutralizing-antibody-based treatments offer a broad range of applications, including the prevention and treatment of acute infectious diseases. Hundreds of SARS-CoV-2 neutralizing antibody studies are currently underway around the world, with some already in clinical applications. The development of SARS-CoV-2 neutralizing antibody opens up a new therapeutic option for COVID-19. We intend to review our current knowledge about antibodies targeting various regions (i.e., RBD regions, non-RBD regions, host cell targets, and cross-neutralizing antibodies), as well as the current scientific evidence for neutralizing-antibody-based treatments based on convalescent plasma therapy, intravenous immunoglobulin, monoclonal antibodies, and recombinant drugs. The functional evaluation of antibodies (i.e., in vitro or in vivo assays) is also discussed. Finally, some current issues in the field of neutralizing-antibody-based therapies are highlighted.

/pdf/review-of-therapeutic-mechanisms-and-applications-based-on-gpgdfca9.pdf

Review of therapeutic mechanisms and applications based on SARS-CoV-2 neutralizing antibodies

RNA viruses, including SARS-CoV-2, evade host immune responses through mutations. As broader T cell responses against multiple viral proteins could minimize the impact of each single amino acid mutation, the breadth of memory T cells would be one essential parameter for effective protection. ABSTRACT T cell immunity is crucial for long-term immunological memory, but the profile of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific memory T cells in individuals who recovered from COVID-19 (COVID-19-convalescent individuals) is not sufficiently assessed. In this study, the breadth and magnitude of SARS-CoV-2-specific T cell responses were determined in COVID-19-convalescent individuals in Japan. Memory T cells against SARS-CoV-2 were detected in all convalescent individuals, and those with more severe disease exhibited a broader T cell response relative to cases with mild symptoms. Comprehensive screening of T cell responses at the peptide level was conducted for spike (S) and nucleocapsid (N) proteins, and regions frequently targeted by T cells were identified. Multiple regions in S and N proteins were targeted by memory T cells, with median numbers of target regions of 13 and 4, respectively. A maximum of 47 regions were recognized by memory T cells for an individual. These data indicate that SARS-CoV-2-convalescent individuals maintain a substantial breadth of memory T cells for at least several months following infection. Broader SARS-CoV-2-specific CD4+ T cell responses, relative to CD8+ T cell responses, were observed for the S but not the N protein, suggesting that antigen presentation is different between viral proteins. The binding affinity of predicted CD8+ T cell epitopes to HLA class I molecules in these regions was preserved for the Delta variant and at 94 to 96% for SARS-CoV-2 Omicron subvariants, suggesting that the amino acid changes in these variants do not have a major impact on antigen presentation to SARS-CoV-2-specific CD8+ T cells. IMPORTANCE RNA viruses, including SARS-CoV-2, evade host immune responses through mutations. As broader T cell responses against multiple viral proteins could minimize the impact of each single amino acid mutation, the breadth of memory T cells would be one essential parameter for effective protection. In this study, breadth of memory T cells to S and N proteins was assessed in COVID-19-convalescent individuals. While broad T cell responses were induced against both proteins, the ratio of N to S proteins for breadth of T cell responses was significantly higher in milder cases. The breadth of CD4+ and CD8+ T cell responses was also significantly different between S and N proteins, suggesting different contributions of N and S protein-specific T cells for COVID-19 control. Most CD8+ T cell epitopes in the immunodominant regions maintained their HLA binding to SARS-CoV-2 Omicron subvariants. Our study provides insights into understanding the protective efficacy of SARS-CoV-2-specific memory T cells against reinfection.

Breadth and Durability of SARS-CoV-2-Specific T Cell Responses following Long-Term Recovery from COVID-19

Abstract The immunity of patients who recover from coronavirus disease 2019 (COVID-19) could be long lasting but persist at a lower level. Thus, recovered patients still need to be vaccinated to prevent reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or its mutated variants. Here, we report that the inactivated COVID-19 vaccine can stimulate immunity in recovered patients to maintain high levels of anti-receptor-binding domain (RBD) and anti-nucleocapsid protein (NP) antibody titers within 9 months, and high neutralizing activity against the prototype, Delta, and Omicron strains was observed. Nevertheless, the antibody response decreased over time, and the Omicron variant exhibited more pronounced resistance to neutralization than the prototype and Delta strains. Moreover, the intensity of the SARS-CoV-2-specific CD4 + T cell response was also increased in recovered patients who received COVID-19 vaccines. Overall, the repeated antigen exposure provided by inactivated COVID-19 vaccination greatly boosted both the potency and breadth of the humoral and cellular immune responses against SARS-CoV-2, effectively protecting recovered individuals from reinfection by circulating SARS-CoV-2 and its variants. 

/pdf/covid-19-vaccination-boosts-the-potency-and-breadth-of-the-1ywf82gr.pdf

COVID-19 vaccination boosts the potency and breadth of the immune response against SARS-CoV-2 among recovered patients in Wuhan

Treatment strategies with combined agency against severe viral pneumonia in patients with advanced cancer.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne virus, prevalent in more than 30 countries worldwide. Human infection by this virus leads to severe illness, with an average case fatality of 40%. There is currently no approved vaccine or drug to treat the disease. Neutralizing antibodies are a promising approach to treat virus infectious diseases. This study generated 37 mouse-derived specific monoclonal antibodies against CCHFV Gc subunit. Neutralization assays using pseudotyped virus and authentic CCHFV identified Gc8, Gc13, and Gc35 as neutralizing antibodies. Among them, Gc13 had the highest neutralizing activity and binding affinity with CCHFV Gc. Consistently, Gc13, but not Gc8 or Gc35, showed in vivo protective efficacy (62.5% survival rate) against CCHFV infection in a lethal mouse infection model. Further characterization studies suggested that Gc8 and Gc13 may recognize a similar, linear epitope in domain II of CCHFV Gc, while Gc35 may recognize a different epitope in Gc. Cryo-electron microscopy of Gc-Fab complexes indicated that both Gc8 and Gc13 bind to the conserved fusion loop region and Gc13 had stronger interactions with sGc-trimers. This was supported by the ability of Gc13 to block CCHFV GP-mediated membrane fusion. Overall, this study provides new therapeutic strategies to treat CCHF and new insights into the interaction between antibodies with CCHFV Gc proteins.

Neutralizing monoclonal antibodies against the Gc fusion loop region of Crimean–Congo hemorrhagic fever virus

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.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202104333

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

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

COVID-19 vaccination boosts the potency and breadth of the immune response against SARS-CoV-2 among recovered patients in Wuhan