Neutralisation of circulating SARS-CoV-2 delta and omicron variants by convalescent plasma and SARS-CoV-2 hyperimmune intravenous human immunoglobulins for treatment of COVID-19

Zahra, Fatema Tuz; Bellusci, Lorenza; Grubbs, Gabrielle; Golding, Hana; Khurana, Surender

doi:10.1136/annrheumdis-2022-222115

Cited by 12 publications

(10 citation statements)

References 9 publications

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“…37,47 At high titers, CCP collected prior to emergence of delta and omicron variants retain in vitro neutralization against these variants. 10,48,49 The same is true for BQ.1.1 and XBB.1 variants with plasma collected after either recent booster or omicron infection. 50 Post-vaccine CCP could thus both treat and prevent the formation of new variants.…”

Section: Discussionmentioning

confidence: 80%

High‐titer post‐vaccine COVID‐19 convalescent plasma for immunocompromised patients during the first omicron surge

Tayyar

Wong

Dahlen

et al. 2023

Transplant Infectious Dis

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Background Transplant and hematologic malignancy patients have high Coronavirus disease 2019 (COVID‐19) mortality and impaired vaccination responses. Omicron variant evades several monoclonal antibodies previously used in immunocompromised patients. Polyclonal COVID‐19 convalescent plasma (CCP) may provide broader neutralizing capacity against new variants at high titers. Vaccination increases severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) titer in convalescent donors. Methods We conducted a retrospective chart review of hospitalized immunocompromised patients with COVID‐19 who received high‐titer CCP during the first omicron surge, collected from vaccinated donors within 6 months of pre‐omicron COVID‐19. Data on safety and outcomes were extracted. Results A total of 44 immunocompromised patients were included, 59.1% with solid organ transplant, 22.7% with hematopoietic cell transplant, 11.4% with hematologic malignancy, and 6.8% with autoimmune disease. Overall, 95% of CCP units transfused were from recently recovered and vaccinated donors and had SARS‐CoV‐2 antibody results 8‐ to 37‐fold higher than the Food and Drug Administration's cutoff for high‐titer CCP. There were two mild transfusion reactions. A total of 30‐day mortality was 4.5%. There were no differences in 100‐day mortality by underlying diagnosis, levels of immunosuppression, and timing of CCP administration. Patients with higher immunosuppression had significantly higher mean World Health Organization clinical progression scores at 30‐day post‐CCP compared to those with lower immunosuppression. Conclusions CCP is a safe, globally available treatment for immunocompromised patients with COVID‐19. Mortality was lower in our cohort than that of COVID‐19 patients with similar immunocompromising conditions. Post‐vaccine CCP with very high titers should be prioritized for study in immunocompromised patients. Post‐vaccine CCP has the potential to keep pace with new variants by overcoming mutations at sufficiently high titer.

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Section: Discussionmentioning

confidence: 80%

High‐titer post‐vaccine COVID‐19 convalescent plasma for immunocompromised patients during the first omicron surge

Tayyar

Wong

Dahlen

et al. 2023

Transplant Infectious Dis

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“…This PDF file includes: Materials and Methods Figs. S1 to S11 Tables S1 to S3 References (60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73) Other Supplementary Material for this manuscript includes the following: Data file S1 MDAR Reproducibility Checklist View/request a protocol for this paper from Bio-protocol.…”

Section: Supplementary Materialsmentioning

confidence: 99%

Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine

et al. 2023

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The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has placed an imperative on the development of countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent monoclonal antibodies (mAbs) that neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells (MBCs) for at least 1 year after primary vaccination. Antibodies generated from these antigen-specific MBCs at 5 to 12 months after vaccination displayed greater potency and breadth relative to those identified at 1.4 months. Fifteen of the 338 (about 4.4%) antibodies isolated at 1.4 to 6 months after the primary vaccination showed potency against SARS-CoV-2 BA.1, despite the absence of serum BA.1 neutralization. 25F9 and 20A7 neutralized authentic clade 1 sarbecoviruses (SARS-CoV, WIV-1, SHC014, SARS-CoV-2 D614G, BA.1, and Pangolin-GD) and vesicular stomatitis virus–pseudotyped clade 3 sarbecoviruses (BtKY72 and PRD-0038). 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1, and XBB. Crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved sites within the RBD. Prophylactic protection of 25F9, 20A7, and 27A12 was confirmed in mice, and administration of 25F9 particularly provided complete protection against SARS-CoV-2, BA.1, SARS-CoV, and SHC014 challenge. These data underscore the extremely potent and broad activity of these mAbs against sarbecoviruses.

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“…Also, just like CPT, the source(s) of the IVIg, whether it be from vaccinated individuals or convalescing patients, would have an impact on the ability to bind and neutralize variants, especially when new variants such as Omicron come along that are highly resistant to most antibodies from vaccinees or convalescent patients, as noted previously. A recent study showed that with proper screening for relevant donors and using only high titer (i.e., > 1:320) preparations, that hyperimmune IVIg could be beneficial for use in the pre-exposure prophylaxis and treatment of post-exposure/seronegative patient groups, even in areas in which Delta or Omicron (BA.1) variants are prevalent [ 184 ].…”

Section: Convalescent Patient and Polyclonal Therapeutic Approachesmentioning

confidence: 99%

Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants

Strohl

et al. 2022

BioDrugs

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The COVID-19 pandemic is now approaching 2 years old, with more than 440 million people infected and nearly six million dead worldwide, making it the most significant pandemic since the 1918 influenza pandemic. The severity and significance of SARS-CoV-2 was recognized immediately upon discovery, leading to innumerable companies and institutes designing and generating vaccines and therapeutic antibodies literally as soon as recombinant SARS-CoV-2 spike protein sequence was available. Within months of the pandemic start, several antibodies had been generated, tested, and moved into clinical trials, including Eli Lilly’s bamlanivimab and etesevimab, Regeneron’s mixture of imdevimab and casirivimab, Vir’s sotrovimab, Celltrion’s regdanvimab, and Lilly’s bebtelovimab. These antibodies all have now received at least Emergency Use Authorizations (EUAs) and some have received full approval in select countries. To date, more than three dozen antibodies or antibody combinations have been forwarded into clinical trials. These antibodies to SARS-CoV-2 all target the receptor-binding domain (RBD), with some blocking the ability of the RBD to bind human ACE2, while others bind core regions of the RBD to modulate spike stability or ability to fuse to host cell membranes. While these antibodies were being discovered and developed, new variants of SARS-CoV-2 have cropped up in real time, altering the antibody landscape on a moving basis. Over the past year, the search has widened to find antibodies capable of neutralizing the wide array of variants that have arisen, including Alpha, Beta, Gamma, Delta, and Omicron. The recent rise and dominance of the Omicron family of variants, including the rather disparate BA.1 and BA.2 variants, demonstrate the need to continue to find new approaches to neutralize the rapidly evolving SARS-CoV-2 virus. This review highlights both convalescent plasma- and polyclonal antibody-based approaches as well as the top approximately 50 antibodies to SARS-CoV-2, their epitopes, their ability to bind to SARS-CoV-2 variants, and how they are delivered. New approaches to antibody constructs, including single domain antibodies, bispecific antibodies, IgA- and IgM-based antibodies, and modified ACE2-Fc fusion proteins, are also described. Finally, antibodies being developed for palliative care of COVID-19 disease, including the ramifications of cytokine release syndrome (CRS) and acute respiratory distress syndrome (ARDS), are described. Supplementary Information The online version contains supplementary material available at 10.1007/s40259-022-00529-7.

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Neutralisation of circulating SARS-CoV-2 delta and omicron variants by convalescent plasma and SARS-CoV-2 hyperimmune intravenous human immunoglobulins for treatment of COVID-19

Abstract: To cite Zahra FT, Bellusci L, Grubbs G, et al. Ann Rheum Dis Epub ahead of print: [please include Day Month Year].

Cited by 12 publications

References 9 publications

High‐titer post‐vaccine COVID‐19 convalescent plasma for immunocompromised patients during the first omicron surge

High‐titer post‐vaccine COVID‐19 convalescent plasma for immunocompromised patients during the first omicron surge

Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine

Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants

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