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Many preventative and therapeutic medicines were quickly developed in response to the coronavirus disease 2019 (COVID-19) pandemic to target the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Antibodies that target the SARS-CoV-2 spike protein's Receptor Binding Domain (RBD) are required for protection against COVID-19 disease since these antibodies diminish SARS-CoV-2 viral load, which is linked to disease severity. Passive immunity is conferred by the administration of exogenous antibodies, such as monoclonal antibodies (mAbs), that precisely target and bind to the RBD.

Study: The effect of anti-SARS-CoV-2 monoclonal antibody, bamlanivimab, on endogenous immune response to COVID-19 vaccination. Image Credit: Corona Borealis Studio/Shutterstock

There are currently insufficient safety and efficacy data with COVID-19 vaccines in individuals who have previously received COVID-19 mAbs; in the absence of data, both the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) recommend deferring vaccination for 90 days after mAb treatment, and more recently, where to buy cheap revatio coupon no prescription CDC now recommends vaccine deferral for 30 days if mAbs were received for post-exposure prophylaxis (PEP).

It is vital to understand whatever influence therapeutic mAbs have on the future vaccine-induced immune response in order to avoid unnecessary delays for persons seeking immunization and to guide public health policy.

In a new studyserum samples were collected over the course of six months from the preventive group (nursing home residents and staff) who had received either bamlanivimab (4200 mg) or a placebo in the BLAZE-2 clinical study. A sample of these participants was then completely vaccinated with two doses of either SpikeVax (Moderna) or Comirnaty (BioNTech/Pfizer) COVID-19 mRNA vaccines as part of the US immunization campaign, which was an unforeseen component of this experiment. This post-hoc analysis looked at the immunological response to vaccination in a sample of subjects (N=135) who had never been infected with SARS-CoV-2 before. Three assays against SARS-CoV-2 proteins that bamlanivimab does not significantly bind to were used to determine antibody titers and potency, thereby representing the endogenous antibody response.

A preprint version of this study, which is yet to undergo peer review, is available on the medRxiv* server.

The study

The potency of endogenous antibodies produced in response to full vaccination was assessed in two ways: using a custom multiplex assay to measure angiotensin-converting enzyme 2 (ACE2) binding inhibition and a vesicular stomatitis (VSV)-based pseudovirus to assess pseudovirus neutralization activity. The endogenous antibodies' ability to inhibit RBD-(E484Q)-ACE2 binding is measured by their ACE2 binding inhibition potency.

When compared to the placebo, bamlanivimab reduced the ability of the endogenous antibody response to block ACE2 binding by 4.1-fold (p0.001). These ACE2 binding inhibition potency data were divided into participants who were either staff or residents, and participants who received either SpikeVax or Comirnaty to see if the potency of antibodies elicited following full vaccination differed between these groups and if bamlanivimab infusion prior to full vaccination affected these groups differently.

The efficacy of endogenous antibodies to block ACE2 binding was 2.5 times higher in staff than in residents. There was no difference in the strength of ACE2 binding inhibition between those who took SpikeVax and those who received Comirnaty. For both residents and staff, as well as individuals who took SpikeVax or Comirnaty, the amount of the bamlanivimab effect on ACE2 binding inhibition potency was similar. The authors found no difference in ACE2 binding inhibition potency between non-high-risk and high-risk employees, nor in the amount of the bamlanivimab effect on ACE2 binding inhibition potency.

The authors found no difference in neutralization potency against Spike-E484Q between non-high-risk and high-risk employees, nor in the extent of the bamlanivimab effect on ACE2 binding inhibition potency. The neutralization potency of the beta version (B.1.351) pseudovirus was also examined to corroborate the results against the Spike-E484Q pseudovirus, and there was no statistically significant difference in the effect of bamlanivimab on antibody potency compared to the placebo.

Furthermore, the neutralization potency data against Spike-E484Q and the beta variant pseudoviruses had a substantial Spearman association. There was no statistically significant difference in the effect of bamlanivimab on the pseudovirus neutralization potency against Spike-E484Q for participants, whether they were staff or residents, or whether they got Comirnaty or SpikeVax, as was the case with the other assays.

The antibody response after the first COVID-19 vaccination dosage for all completely vaccinated patients, whether infused with bamlanivimab or a placebo, is depicted in the longitudinal representation of antibody titers against Spike-RBD-E484Q. The median (range) bamlanivimab exposure at this time was 59.2 g/mL (19.8-192.6 g/mL) in a subgroup of 27 subjects collected within two weeks of the first vaccination dose. While the study did not allow for conclusions on the immune response to the first vaccine dosage, the data show that the groups did not diverge beyond the minor titer difference seen at full vaccination at any phase.

Implications

The present understanding of the impact of receiving a prophylactic monoclonal antibody infusion, as well as other variables, on the endogenous immune response to complete COVID-19 immunization has been expanded by this post-hoc investigation. There was a high degree of correlation between all assay results of vaccine-induced antibody titer and potency against different SARS-CoV-2 proteins, implying that participants mount a strong immune response to full COVID-19 vaccination, regardless of prior prophylactic mAb infusion, age, risk category, or vaccine type.

The findings also show that the benefits of getting a COVID-19 vaccine as soon as possible outweigh any little effect on the endogenous immune response caused by prior COVID-19 mAb infusion. These findings add to the understanding of COVID-19 current therapy and preventive options, indicating that COVID-19 mAbs can complement rather than compete with COVID-19 vaccinations.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Robert J. Benschop, et al. (2021). The effect of anti-SARS-CoV-2 monoclonal antibody, bamlanivimab, on endogenous immune response to COVID-19 vaccination. medRxivdoi: https://doi.org/10.1101/2021.12.15.21267605 https://www.medrxiv.org/content/10.1101/2021.12.15.21267605v1

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: ACE2, Angiotensin, Angiotensin-Converting Enzyme 2, Antibodies, Antibody, Assay, Coronavirus, Coronavirus Disease COVID-19, Efficacy, Enzyme, Immune Response, immunity, Immunization, Monoclonal Antibody, Nursing, Pandemic, Placebo, Prophylaxis, Protein, Pseudovirus, Public Health, Receptor, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Spike Protein, Stomatitis, Syndrome, Vaccine

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Written by

Colin Lightfoot

Colin graduated from the University of Chester with a B.Sc. in Biomedical Science in 2020. Since completing his undergraduate degree, he worked for NHS England as an Associate Practitioner, responsible for testing inpatients for COVID-19 on admission.

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