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

Benschop, Robert J.; Tuttle, Jay; Zhang, Lin; Poorbaugh, Josh; Kallewaard, Nicole L.; Vaillancourt, Peter; Crisp, Melissa; Trinh, Thi Ngoc Vy; Freitas, Joshua J.; Beasley, Stephanie; Daniels, Montanea; Haustrup, Natalie; Higgs, Richard E.; Nirula, Ajay; Cohen, Myron S.; Marovich, Mary

doi:10.1126/scitranslmed.abn3041

Cited by 28 publications

(20 citation statements)

References 53 publications

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“…There were no differences in non-RBD IgG titers between the mAb and placebo groups at day 28. In contrast, it was found that following a higher (4200 mg), prophylactic dose of bamlanivimab, individuals without a history of SARS-CoV-2 infection had lower antibody titers after two doses of a COVID-19 mRNA vaccine than individuals who had received placebo control (5). However, antibody titers differed between the groups by twofold or less, which was considered a clinically insignificant difference (5).…”

Section: Discussionmentioning

confidence: 99%

Bamlanivimab therapy for acute COVID-19 does not blunt SARS-CoV-2–specific memory T cell responses

Ramirez¹,

Grifoni²,

Weiskopf³

et al. 2022

JCI Insight

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Despite the widespread use of SARS-CoV-2-specific monoclonal antibody (mAb) therapy for the treatment of acute COVID-19, the impact of this therapy on the development of SARS-CoV-2-specific T cell responses has been unknown, resulting in uncertainty as to whether anti-SARS-CoV-2 mAb administration may result in failure to generate immune memory. Alternatively, it has been suggested that SARS-CoV-2specific mAb may enhance adaptive immunity to SARS-CoV-2 via a "vaccinal effect." Bamlanivimab (Eli Lilly) is a recombinant human IgG1 that was granted FDA emergency use authorization for the treatment of mild to moderate COVID-19 in those at high risk for progression to severe disease. Here, we compared SARS-CoV-2 specific CD4 + and CD8 + T cell responses of 95 individuals from the ACTIV-2/A5401 clinical trial 28 days after treatment with 700 mg bamlanivimab versus placebo. SARS-CoV-2-specific T cell responses were evaluated using activation induced marker (AIM) assays in conjunction with intracellular cytokine staining (ICS). We demonstrate that most individuals with acute COVID-19 develop SARS-CoV-2specific T cell responses. Overall, our findings suggest that the quantity and quality of SARS-CoV-2-specific T cell memory was not diminished in individuals who received bamlanivimab for acute COVID-19. Receipt of bamlanivimab during acute COVID-19 neither diminished nor enhanced SARS-CoV-2-specific cellular immunity.

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Section: Discussionmentioning

confidence: 99%

Bamlanivimab therapy for acute COVID-19 does not blunt SARS-CoV-2–specific memory T cell responses

Ramirez¹,

Grifoni²,

Weiskopf³

et al. 2022

JCI Insight

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“…Our study showed, as did one prior study, a decrease in IgG Abs to some SARS-CoV-2 Ags in children but not adults (4), but the prior study did not evaluate nAbs, which we show decreased less frequently in children than adults. We used a surrogate neutralizing assay in this study that was previously been reported to be strongly correlated with levels of nAb measured with pseudovirus assays (20). Two prior studies showed lower nAb titers in children than adults with SARS-CoV-2 infection, one of which included only hospitalized children (11) and the other included hospitalized children and children with asymptomatic infection (17).…”

Section: Discussionmentioning

confidence: 99%

“…Luminex xMAP technology is a multiplex, flow cytometrybased platform that allows the simultaneous quantitation of many protein analytes in a single reaction (18). A custom Luminex-based assay was developed to measure serology and Ab ACE2receptor-binding domain (RBD) binding inhibition in a single assay as previously described (19,20). Surrogate nAbs.…”

Section: Serological Assaysmentioning

confidence: 99%

Level and Duration of IgG and Neutralizing Antibodies to SARS-CoV-2 in Children with Symptomatic or Asymptomatic SARS-CoV-2 Infection

et al. 2022

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There are conflicting data about level and duration of Abs to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children after symptomatic or asymptomatic infection. In this human population, we enrolled adults and children in a prospective 6-mo study in the following categories: 1) symptomatic, SARS-CoV-2 PCR + (SP + ; children, n 5 8; adults, n 5 16), 2) symptomatic, PCR À , or untested (children, n 5 27), 3) asymptomatic exposed (children, n 5 13), and 4) asymptomatic, no known exposure (children, n 5 19). Neutralizing Abs (nAbs) and IgG Abs to SARS-CoV-2 Ags and spike protein variants were measured by multiplex serological assay. All SP + children developed nAb, whereas 81% of SP + adults developed nAb. Decline in the presence of nAb over 6 mo was not significant in symptomatic children (100 to 87.5%; p 5 0.32) in contrast to adults (81.3 to 50.0%; p 5 0.03). Among children with nAb (n 5 22), nAb titers and change in titers over 6 mo were similar in symptomatic and asymptomatic children. In children and adults, nAb levels postinfection were 10-fold lower than those reported after SARS-CoV-2 mRNA vaccination. Levels of IgG Abs in children to SARS-CoV-2 Ags and spike protein variants were similar to those in adults. IgG levels to primary Ags decreased over time in children and adults, but levels to three spike variants decreased only in children. Children with asymptomatic or symptomatic SARS-CoV-2 infection develop nAbs that remain present longer than in adults but wane in titer over time and broad IgG Abs that also wane in level over time. However, nAb levels were lower postinfection than those reported after immunization. ImmunoHorizons, 2022, 6: 408-415.

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“…These results emphasize the utility of mAbs regardless of the proportion vaccinated, and have public health implications regardless of the pandemic source; as the effective reproductive number, R ( t ), approaches 1, incremental benefits from an antiviral may still provide momentum in further reducing infections, thereby bringing R ( t ) below 1. Recent evidence also suggests that receiving a mAb for COVID‐19 prophylaxis does not affect the immune response that results from subsequent vaccination, 34 strengthening the combined role for these strategies in pandemic management.…”

Section: Discussionmentioning

confidence: 99%

Assessing the Combined Public Health Impact of Pharmaceutical Interventions on Pandemic Transmission and Mortality: An Example in SARS CoV‐2

Kamal

Kuznik

Qi³

et al. 2022

Clin Pharma and Therapeutics

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To assess the combined role of anti‐viral monoclonal antibodies (mAbs) and vaccines in reducing severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) transmission and mortality in the United States, an agent‐based model was developed that accounted for social contacts, movement/travel, disease progression, and viral shedding. The model was calibrated to coronavirus disease 2019 (COVID‐19) mortality between October 2020 and April 2021 (aggressive pandemic phase), and projected an extended outlook to estimate mortality during a less aggressive phase (April–August 2021). Simulated scenarios evaluated mAbs for averting infections and deaths in addition to vaccines and aggregated non‐pharmaceutical interventions. Scenarios included mAbs as a treatment of COVID‐19 and for passive immunity for postexposure prophylaxis (PEP) during a period when variants were susceptible to the mAbs. Rapid diagnostic testing paired with mAbs was evaluated as an early treatment‐as‐prevention strategy. Sensitivity analyses included increasing mAb supply and vaccine rollout. Allocation of mAbs for use only as PEP averted up to 14% more infections than vaccine alone, and targeting individuals ≥ 65 years averted up to 37% more deaths. Rapid testing for earlier diagnosis and mAb use amplified these benefits. Doubling the mAb supply further reduced infections and mortality. mAbs provided benefits even as proportion of the immunized population increased. Model projections estimated that ~ 42% of expected deaths between April and August 2021 could be averted. Assuming sensitivity to mAbs, their use as early treatment and PEP in addition to vaccines would substantially reduce SARS‐CoV‐2 transmission and mortality even as vaccination increases and mortality decreases. These results provide a template for informing public health policy for future pandemic preparedness.

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

Cited by 28 publications

References 53 publications

Bamlanivimab therapy for acute COVID-19 does not blunt SARS-CoV-2–specific memory T cell responses

Bamlanivimab therapy for acute COVID-19 does not blunt SARS-CoV-2–specific memory T cell responses

Level and Duration of IgG and Neutralizing Antibodies to SARS-CoV-2 in Children with Symptomatic or Asymptomatic SARS-CoV-2 Infection

Assessing the Combined Public Health Impact of Pharmaceutical Interventions on Pandemic Transmission and Mortality: An Example in SARS CoV‐2

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