Standardized two-step testing of antibody activity in COVID-19 convalescent plasma

Gilchuk, Pavlo; Thomsen, Isaac; Yoder, Sandra; Brady, Eric; Chappell, James D.; Stevens, Laura J.; Denison, Mark R.; Sutton, Rachel E.; Chen, Rita E.; VanBlargan, Laura A.; Suryadevara, Naveen Chandra; Zost, Seth J.; Schmitz, Jonathan E.; Pulley, Jill M.; Diamond, Michael S.; Rhoads, Jillian P.; Bernard, Gordon R.; Self, Wesley H.; Rice, Todd W.; Wheeler, Allison P.; Crowe, James E.

doi:10.1016/j.isci.2021.103602

Cited by 7 publications

(3 citation statements)

References 64 publications

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“…Another approach would be to use an external standard, such as that provided by the World Health Organization (WHO), to calibrate the results of assays performed under different conditions ( 61 , 66 ). However, this reagent’s limited and nonrenewable nature currently limits its wide-scale utilization ( 67 ). The marked loss of activity of many MAbs against the Omicron variants also underscores the importance of developing MAbs that target conserved regions of spike that are not targeted by the antibodies produced in infected persons.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis

et al. 2022

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“…Another approach is to use an external standard, such as that provided by the World Health Organization (WHO) to calibrate the results of assays performed under different conditions [49,59]. However, this reagent's limited and non-renewable nature currently limits its widescale utilization [60]. The marked loss of activity of many mAbs against the Omicron variant also underscores the importance of developing mAbs that target conserved regions of spike that are not targeted by the Abs produced in infected persons.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-Analysis

Tao¹,

Tzou²,

Pond³

et al. 2022

Preprint

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SARS-CoV-2 Omicron variants contain many mutations in its spike receptor binding domain, the target of all authorized monoclonal antibodies (mAbs). Determining the extent to which Omicron variants reduced mAb susceptibility is critical to preventing and treating COVID-19. We systematically reviewed PubMed and three preprint servers, last updated February 22, 2022, of the in vitro activity of authorized mAbs against the Omicron variants. Thirty-three studies were eligible including 33 containing Omicron BA.1 susceptibility data and five that also contained Omicron BA.2 susceptibility data. The first two authorized mAb combinations, bamlanivimab/etesevimab and casirivimab/imdevimab, were inactive against the Omicron BA.1 and BA.2 variants. In 24 studies, sotrovimab (third authorized mAb) displayed a median 4.1-fold (IQR: 2.4-7.6) reduced activity against Omicron BA.1 and, in four studies, a median 26-fold (IQR:16-35) reduced activity against Omicron BA.2. In 18 studies, cilgavimab and tixagevimab independently displayed median reductions in activity of >300-fold against Omicron BA.1, while in ten studies, the cilgavimab/tixagevimab combination (fourth authorized mAb preparation) displayed a median 63-fold (IQR: 26-145) reduced activity against Omicron BA.1. In two studies, cilgavimab was approximately 100-fold more susceptible to BA.2 than to BA.1. In two studies, bebtelovimab, the most recently authorized mAb, was fully active against both the Omicron variants. Disparate results between assays were common as evidenced by a median 42-fold range (IQR: 25-625) in IC50 between assays for the eight authorized individual mAbs and three authorized mAb combinations. Highly disparate results between published assays indicates a need for improved mAb susceptibility test standardization or inter-assay calibration.

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“…A similar form of passive immunization may be advisable for the patient in question when infected. Alternatively, transfusion of hyperimmunoglobulin of selected plasma donors containing high levels of virus-neutralizing anti-RBD antibodies may be practicable, since the patient was, at least until recently, dependent on general immunoglobulin infusion [ 27 ] due to treatment-induced hypogammaglobulinemia.…”

Section: Discussionmentioning

confidence: 99%

Lack of Induction of RBD-Specific Neutralizing Antibodies despite Repeated Heterologous SARS-CoV-2 Vaccination Leading to Seroconversion and Establishment of T Cell-Specific Memory in a Patient in Remission of Multiple Myeloma

et al. 2022

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Background: Prophylactic vaccination against infectious diseases may induce a state of long-term protection in the otherwise healthy host. However, the situation is less predictable in immunocompromised patients and may require adjustment of vaccination schedules and/or basic therapy. Methods: A patient in full remission of multiple myeloma since the last three years and on long-term maintenance therapy with pomalidomide, a drug inhibiting angiogenesis and myeloma cell growth, was vaccinated twice with Comirnaty followed by two vaccinations with Vaxzevria. Seroconversion and SARS-CoV-2-specific cellular responses were monitored. Results: No signs of seroconversion or T cellular memory were observed after the first “full immunization” with Comirnaty. Consequently, long-term-maintenance therapy with Pomalidomide was stopped and two additional shots of Vaxzevria were administered after which the patient seroconverted with Spike(S)-protein specific antibody levels reaching 49 BAU/mL, mild S-peptide pool-specific T cell proliferation, effector cytokine production (IL-2, IL-13), and T cellular activation with increased numbers of CD3+CD4+CD25+ T cells as compared to vaccinated and non-vaccinated control subjects. However, despite suspension of immunosuppression and administration of in total four consecutive heterologous SARS-CoV-2 vaccine shots, the patient did not develop neutralizing RBD-specific antibodies. Conclusions: Despite immunomonitoring-based adjustment of vaccination and/or therapy schedules vaccination success, with clear correlates of protection, the development of RBD-specific antibodies could not be achieved in the immunocompromised patient with current SARS-CoV-2 vaccines. Thus, our report emphasizes the need for improved active and passive immunization strategies for SARS-CoV-2 infections.

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Standardized two-step testing of antibody activity in COVID-19 convalescent plasma

Cited by 7 publications

References 64 publications

Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis

Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis

Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-Analysis

Lack of Induction of RBD-Specific Neutralizing Antibodies despite Repeated Heterologous SARS-CoV-2 Vaccination Leading to Seroconversion and Establishment of T Cell-Specific Memory in a Patient in Remission of Multiple Myeloma

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