Time to knock monoclonal antibodies off the platform for patients hospitalised with COVID-19

Shapiro, Adrienne E.; Ignacio, Rachel A. Bender

doi:10.1016/s1473-3099(21)00762-3

Cited by 11 publications

(9 citation statements)

References 10 publications

(11 reference statements)

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“…Whereas effective SARS-CoV-2-specific mAb treatment for hospitalized patients has remained elusive, clinical success has been obtained in the treatment of outpatients with mild or moderate COVID-19 with anti-SARS-CoV-2 monoclonal antibodies ( 35 , 36 ). In addition to therapeutic treatment, the development of these monoclonal antibodies may also be of value for preventive treatment of seronegative individuals including those that do not make endogenous antibodies in response to either vaccination or infection ( 37 ). The antigenic evolution of SARS-CoV-2 has posed a formidable challenge to the development of monoclonal antibodies for the treatment and prevention of COVID-19.…”

Section: Discussionmentioning

confidence: 99%

An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern

Hurdiss

Drabek

et al. 2022

Sci. Immunol.

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The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential through mutations at key antigenic sites on the spike protein. Many of these mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of therapeutic antibodies that were effective against other Variants of Concern (VOCs) earlier in the pandemic. Here, we identified a receptor-blocking human monoclonal antibody, 87G7, that retained potent in vitro neutralizing activity against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) VOCs. Using cryo-electron microscopy and site-directed mutagenesis experiments, we showed that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protected mice and/or hamsters prophylactically against challenge with all current SARS-CoV-2 VOCs, and showed therapeutic activity against SARS-CoV-2 challenge in both animal models. Our findings demonstrate that 87G7 holds promise as a prophylactic or therapeutic agent for COVID-19 that is more resilient to SARS-CoV-2 antigenic diversity.

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Section: Discussionmentioning

confidence: 99%

An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern

Hurdiss

Drabek

et al. 2022

Sci. Immunol.

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“…However, there are discouraging results for SOTRs persistently anergic after the 3rd dose after application of a 4th dose [ 31 , 32 ]. For such patients, passive transfer of anti-SARS-CoV-2 monoclonal antibodies might be the only option [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Third dose of the BNT162b2 vaccine in cardiothoracic transplant recipients: predictive factors for humoral response

et al. 2022

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Background We report the results of a prospective study on the immunogenicity of a 3rd dose of BNT162b2 in thoracic organ recipients with no or minimal response following a two-dose BNT162b2 vaccination scheme. Methods A total of 243 transplant recipients received a homologue 3rd dose. Anti-SARS-CoV2-immunoglobulins (IgGs) were monitored immediately before (T1), 4 weeks (T2) as well as 2 and 4 months after the 3rd dose. Neutralizing antibody capacity (NAC) was determined at T2. To reveal predictors for detectable humoral response, patients were divided into a positive response group (n = 129) based on the combined criteria of IgGs and NAC above the defined cut-offs at T2—and a group with negative response (n = 114), with both, IgGs and NAC beyond the cut-offs. Results The 3rd dose induced a positive humoral response in 53% of patients at T2, 47% were still non-responsive. Sero-positivity was significantly stronger in patients who presented with weak, but detectable IgGs already prior to the booster (T1), when compared to those with no detectable response at T1. Multivariable analysis identified age > 55 years, a period since transplantation < 2 years, a reduced glomerular filtration rate, a triple immunosuppressive regimen, and the use of tacrolimus and of mycophenolate as independent risk factors for lack of humoral response. Conclusions Our data indicate that a lack of immunogenicity is linked to the type and extent of maintenance immunosuppression. The necessity of the cumulative immunosuppressive regimen might individually be questioned and possibly be reduced to enhance the chance of an immune response following an additional booster dose.

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“…Whereas effective SARS-CoV-2-specific mAb treatment for hospitalized patients has remained elusive, clinical success has been obtained in the treatment of outpatients with mild or moderate COVID-19 with anti-SARS-CoV-2 monoclonal antibodies ( 36, 37 ). In addition to therapeutic treatment, the development of these monoclonal antibodies may also be of value for preventive treatment of seronegative individuals including those that do not make endogenous antibodies in response to either vaccination or infection ( 38 ). The antigenic evolution of SARS-CoV-2 has posed a formidable challenge to the development of monoclonal antibodies for the treatment and prevention of COVID-19.…”

Section: Main Textmentioning

confidence: 99%

An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants

Hurdiss

Drabek

et al. 2022

Preprint

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The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential. Many of its mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of most therapeutic monoclonal antibodies. Here we describe a receptor-blocking human monoclonal antibody, 87G7, that retains ultrapotent neutralization against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) Variants-of-Concern (VOCs). Structural analysis reveals that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protects mice and/or hamsters against challenge with all current SARS-CoV-2 VOCs. Our findings may aid the development of sustainable antibody-based strategies against COVID-19 that are more resilient to SARS-CoV-2 antigenic diversity.

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Time to knock monoclonal antibodies off the platform for patients hospitalised with COVID-19

Cited by 11 publications

References 10 publications

An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern

An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern

Third dose of the BNT162b2 vaccine in cardiothoracic transplant recipients: predictive factors for humoral response

An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants

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