Endogenous Antibody Responses to SARS-CoV-2 in Patients With Mild or Moderate COVID-19 Who Received Bamlanivimab Alone or Bamlanivimab and Etesevimab Together

Wang, Qisheng; Poorbaugh, Josh; Dougan, Michael; Chen, Peter; Gottlieb, Robert L; Huhn, Gregory; Beasley, Stephanie; Daniels, Montanea; Trinh, Thi Ngoc Vy; Crisp, Melissa; Freitas, Joshua J.; Vaillancourt, Peter; Patel, Dipak R.; Nirula, Ajay; Kallewaard, Nicole L.; Higgs, Richard E.; Benschop, Robert J.

doi:10.3389/fimmu.2021.790469

Cited by 18 publications

(16 citation statements)

References 28 publications

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“…Our study agrees with the recent report of Zhang et al [ 33 ]. That study examined the endogenous anti-SARS-CoV-2 antibody response in BAM and BAM + ETE treated subjects by measuring antibody titers against portions of the spike protein not recognized by the mAb.…”

Section: Discussionsupporting

confidence: 94%

“…A recent mouse study showed that passive antibody suppressed not only the IgM response but also the IgG and memory B cell response [ 22 ]. The reduced antibody titers reported at 85 days after mAb treatment by Zhang et al [ 33 ] suggests this might be the case. Still, this has yet to be demonstrated in humans and would apply only to the humoral response.…”

Section: Discussionmentioning

confidence: 99%

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Effect of monoclonal antibody therapy on the endogenous SARS-CoV-2 antibody response

Kim

Dimcheff

Siler

et al. 2022

Clinical Immunology

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Effect of monoclonal antibody therapy on the endogenous SARS-CoV-2 antibody response

Kim

Dimcheff

Siler

et al. 2022

Clinical Immunology

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“…Therefore, there was the potential for bamlanivimab to markedly reduce the endogenous immune response to COVID-19 vaccination. However, similar to previous findings ( 53 ), any reduction in antigen load due to therapeutic mAbs was not sufficient to severely blunt the immune response, in this case to COVID-19 vaccination.…”

Section: Discussionsupporting

confidence: 88%

“…As such, most participants far exceeded the in vitro estimated IC90 (4.1 μg/mL) at the time of vaccination ( 30 ). Therapeutic mAbs for COVID-19 are known to reduce viral load ( 7 , 52 ) and we have previously shown that high viral load is associated with high antibody titers ( 53 ). Therefore, there was the potential for bamlanivimab to markedly reduce the endogenous immune response to COVID-19 vaccination.…”

Section: Discussionmentioning

confidence: 99%

The anti–SARS-CoV-2 monoclonal antibody bamlanivimab minimally affects the endogenous immune response to COVID-19 vaccination

et al. 2022

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As the coronavirus disease 2019 (COVID-19) pandemic evolves and vaccine rollout progresses, the availability and demand for monoclonal antibodies for the prevention and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also accelerating. This longitudinal serological study evaluated the magnitude and potency of the endogenous antibody response to COVID-19 vaccination in participants who first received a COVID-19 monoclonal antibody in a prevention study. Over the course of six months, serum samples were collected from a population of nursing home residents and staff enrolled in a clinical trial who were randomized to either bamlanivimab treatment or placebo. In an unplanned component of this trial, a subset of these participants was subsequently fully vaccinated with two doses of either SpikeVax (Moderna) or Comirnaty (BioNTech/Pfizer) COVID-19 mRNA vaccines. This post-hoc analysis assessed the immune response to vaccination for 135 participants without prior SARS-CoV-2 infection. Antibody titers and potency were assessed using three assays against SARS-CoV-2 proteins that bamlanivimab does not efficiently bind to, thereby reflecting the endogenous antibody response. All bamlanivimab and placebo recipients mounted a robust immune response to full COVID-19 vaccination, irrespective of age, risk-category, and vaccine type with any observed differences of uncertain clinical importance. These findings are pertinent for informing public health policy with results that suggest that the benefit of receiving COVID-19 vaccination at the earliest opportunity outweighs the minimal effect on the endogenous immune response due to prior prophylactic COVID-19 monoclonal antibody infusion.

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“…To date, seven mAb neutralizing drugs including bamlanivimab, etesevimab, casirivimab, imdevimab, sotrovimab, cilgavimab, and tixagevimab either as monotherapy or as combination therapy have been approved or received EUAs from the U.S. FDA for the treatment of COVID-19 (Agarwal et al, 2020;Shi et al, 2020a;Zhang et al, 2021c;Nathan et al, 2021). All repurposed drugs with their mechanism of actions against SARS-CoV-2 infections are shown in Table 1.…”

Section: Repurposing Drugs For Covid-19: Concept and Mechanism Of Actionmentioning

confidence: 99%

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies

et al. 2022

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Many drugs are being administered to tackle coronavirus disease 2019 (COVID-19) pandemic situations without establishing clinical effectiveness or tailoring safety. A repurposing strategy might be more effective and successful if pharmacogenetic interventions are being considered in future clinical studies/trials. Although it is very unlikely that there are almost no pharmacogenetic data for COVID-19 drugs, however, from inferring the pharmacokinetic (PK)/pharmacodynamic(PD) properties and some pharmacogenetic evidence in other diseases/clinical conditions, it is highly likely that pharmacogenetic associations are also feasible in at least some COVID-19 drugs. We strongly mandate to undertake a pharmacogenetic assessment for at least these drug–gene pairs (atazanavir–UGT1A1, ABCB1, SLCO1B1, APOA5; efavirenz–CYP2B6; nevirapine–HLA, CYP2B6, ABCB1; lopinavir–SLCO1B3, ABCC2; ribavirin–SLC28A2; tocilizumab–FCGR3A; ivermectin–ABCB1; oseltamivir–CES1, ABCB1; clopidogrel–CYP2C19, ABCB1, warfarin–CYP2C9, VKORC1; non-steroidal anti-inflammatory drugs (NSAIDs)–CYP2C9) in COVID-19 patients for advancing precision medicine. Molecular docking and computational studies are promising to achieve new therapeutics against SARS-CoV-2 infection. The current situation in the discovery of anti-SARS-CoV-2 agents at four important targets from in silico studies has been described and summarized in this review. Although natural occurring compounds from different herbs against SARS-CoV-2 infection are favorable, however, accurate experimental investigation of these compounds is warranted to provide insightful information. Moreover, clinical considerations of drug–drug interactions (DDIs) and drug–herb interactions (DHIs) of the existing repurposed drugs along with pharmacogenetic (e.g., efavirenz and CYP2B6) and herbogenetic (e.g., andrographolide and CYP2C9) interventions, collectively called multifactorial drug–gene interactions (DGIs), may further accelerate the development of precision COVID-19 therapies in the real-world clinical settings.

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Endogenous Antibody Responses to SARS-CoV-2 in Patients With Mild or Moderate COVID-19 Who Received Bamlanivimab Alone or Bamlanivimab and Etesevimab Together

Cited by 18 publications

References 28 publications

Effect of monoclonal antibody therapy on the endogenous SARS-CoV-2 antibody response

Effect of monoclonal antibody therapy on the endogenous SARS-CoV-2 antibody response

The anti–SARS-CoV-2 monoclonal antibody bamlanivimab minimally affects the endogenous immune response to COVID-19 vaccination

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies

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