SARS-CoV-2 spike therapeutic antibodies in the age of variants

Baum, Alina; Kyratsous, Christos A.

doi:10.1084/jem.20210198

Cited by 13 publications

(7 citation statements)

References 13 publications

(24 reference statements)

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Section: Currently Circulating Variants Of Sars-cov-2mentioning

confidence: 99%

“…A cocktail of bamlanivimab and etesevimab is reported to perform better than monotherapy against this variant [64]. Contrary to this, a combination of casirivimab and imdevimab or COV-2130 and COV2196 have shown no loss in neutralization potency against all VOCs including B.1.427 and B.1.429 [65] One broad-spectrum coronavirus antibody, VIR-7831 is effective against these widely circulating VOCs [64]. Neutralization action of casirivimab/imdevimab cocktail and VIR-7831 mAb which was recently reported to provide 85% protection against COVID-19 related hospitalization and deaths, was unaffected by L452R mutation [63].…”

Section: B1427 and B1429mentioning

confidence: 99%

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Emerging SARS-CoV-2 Variants: Genetic Variability and Clinical Implications

2021

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The sudden rise in COVID-19 cases in 2020 and the incessant emergence of fast-spreading variants have created an alarming situation worldwide. Besides the continuous advancements in the design and development of vaccines to combat this deadly pandemic, new variants are frequently reported, possessing mutations that rapidly outcompeted an existing population of circulating variants. As concerns grow about the effects of mutations on the efficacy of vaccines, increased transmissibility, immune escape, and diagnostic failures are few other apprehensions liable for more deadly waves of COVID-19. Although the phenomenon of antigenic drift in new variants of SARS-CoV-2 is still not validated, it is conceived that the virus is acquiring new mutations as a fitness advantage for rapid transmission or to overcome immunological resistance of the host cell. Considerable evolution of SARS-CoV-2 has been observed since its first appearance in 2019, and despite the progress in sequencing efforts to characterize the mutations, their impacts in many variants have not been analyzed. The present article provides a substantial review of literature explaining the emerging variants of SARS-CoV-2 circulating globally, key mutations in viral genome, and the possible impacts of these new mutations on prevention and therapeutic strategies currently administered to combat this pandemic. Rising infections, mortalities, and hospitalizations can possibly be tackled through mass vaccination, social distancing, better management of available healthcare infrastructure, and by prioritizing genome sequencing for better serosurveillance studies and community tracking.

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Section: Currently Circulating Variants Of Sars-cov-2mentioning

confidence: 99%

Section: B1427 and B1429mentioning

confidence: 99%

Emerging SARS-CoV-2 Variants: Genetic Variability and Clinical Implications

2021

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“…The beta variant of SARS-CoV-2 also carries this mutation, which stabilizes the spike protein trimers and thus provides a transmission advantage [ 7 ]. In addition, the N501Y mutation in the spike protein of the SARS-CoV-2 beta variant has been associated with increased viral infectivity and transmission by enhancing the binding affinity of the spike protein to the human ACE2 receptor [ 41 , 42 ]. This increased affinity may explain the higher viral loads observed in individuals infected with the beta variant, as well as its greater transmissibility and vaccine efficacy compared to earlier strains of SARS-CoV-2 [ 43 ], highlighting the importance of continued surveillance and research on the evolution and spread of the SARS-CoV-2 virus.…”

Section: Discussionmentioning

confidence: 99%

Distinctive Combinations of RBD Mutations Contribute to Antibody Evasion in the Case of the SARS-CoV-2 Beta Variant

Kim,

Bae,

Goo

et al. 2023

J. Microbiol. Biotechnol.

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Since its first report in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a grave threat to public health. Virus-specific countermeasures, such as vaccines and therapeutics, have been developed and have contributed to the control of the viral pandemic, which has become endemic. Nonetheless, new variants continue to emerge and could cause a new pandemic. Consequently, it is important to comprehensively understand viral evolution and the roles of mutations in viral infectivity and transmission. SARS-CoV-2 beta variant encode mutations (D614G, N501Y, E484K, and K417N) in the spike which are frequently found in other variants as well. While their individual role in viral infectivity has been elucidated against various therapeutic antibodies, it still remains unclear whether those mutations may act additively or synergistically when combined. Here, we report that N501Y mutation shows differential effect on two therapeutic antibodies tested. Interestingly, the relative importance of E484K and K417N mutations in antibody evasion varies depending on the antibody type. Collectively, these findings suggest that continuous efforts to develop effective antibody therapeutics and combinatorial treatment with multiple antibodies are more rational and effective forms of treatment.

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“…Although hundreds of potent nAbs have been successfully isolated (cf., [ 290 , 321 ]), studies on antibody resistance have demonstrated that rapid viral escape arises with any monotherapy regardless of antibody neutralizing activity and epitope conservation [ 322 – 324 ]. Thus, many researchers and companies have turned to a rational combination of at least two neutralizing antibodies that possess different, non-overlapping epitopes together as a combination therapeutic to provide broader epitope coverage, and hopefully, greater resistance against variants that may arise over time [ 211 , 245 , 261 , 325 ].…”

Section: Anti-sars-cov-2 Igg Antibodiesmentioning

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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SARS-CoV-2 spike therapeutic antibodies in the age of variants

Cited by 13 publications

References 13 publications

Emerging SARS-CoV-2 Variants: Genetic Variability and Clinical Implications

Emerging SARS-CoV-2 Variants: Genetic Variability and Clinical Implications

Distinctive Combinations of RBD Mutations Contribute to Antibody Evasion in the Case of the SARS-CoV-2 Beta Variant

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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