The Antibody Society

the official website of the antibody society

An international non-profit supporting antibody-related research and development.

Prof. Victor Greiff’s webinar is now available On Demand!

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In case you missed Prof. Victor Greiff’s very popular webcast on best practices relating to the conception, analysis and performance of adaptive immune receptor repertoire studies, the On Demand version is now online!

High-throughput sequencing has enabled the capture of adaptive immune receptor repertoire (AIRR) data at unprecedented depth and precision. This webinar gives an in-depth walk-through of best practices to conceive, analyze and perform AIRR studies for answering fundamental immunological questions as well as discovering novel immunodiagnostic biomarkers and design (therapeutic) immune receptors. Specifically, Dr. Greiff addresses current approaches to perform AIRR-compliant AIRR data processing encompassing bulk and single-cell approaches and experimental and bioinformatics quality control. Furthermore, he summarizes the computational methods that have been recently developed to deconstruct the high-dimensional complexity of immune receptor repertoires, e.g., 1) diversity-, 2) phylogenetic-, 3) networks- and 4) machine learning-based methods that have been applied to dissect and understand the diversity, architecture, evolution and antigen specificity of immune repertoires. Finally, Dr. Greiff discusses experimental and computational methods in light of their underlying assumptions, limitations and pitfalls and highlight promising avenues of future research in basic and applied AIRR systems immunology.

Click here to access the On Demand webinar!

Preventing severe disease in Covid-19 patients

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Written by Raquel Barroso Ferro, University of Aberdeen

In April 2020, Vir Biotechnology and GlaxoSmithKline (GSK) began a partnership that has proven fruitful. As announced on March 10, 2021, patients with mild or moderate Covid-19 at high risk of progression to severe disease who were treated with the human monoclonal antibody VIR-7831 (sotrovimab) in the COMET-ICE study (NCT04545060) had a reduction of 85% in hospitalization or death compared to those who received placebo. Although complete details of the ongoing trial are not yet available, this “artificial immunity” offers hope for patients. In particular, such treatment may be beneficial to those who are unable to receive a vaccine or whose immune system is weakened.

Vir and GSK plan to submit an emergency use authorization application in the US and seek authorizations in other countries.

Originally derived from a patient who survived severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, (1) the antibody binds to a highly conserved epitope on the spike glycoprotein shared by both SARS-CoV and the virus causing the current pandemic, SARS-CoV-2. This shared epitope suggests high conservation and its likely importance for viral infection. Binding this epitope may reduce the likelihood of mutational escape, and allow the antibody to neutralize multiple variants that emerge. In fact, according to a pre-print posted March 10, 2021 on BioRxiv, the epitope of VIR-7831 does not overlap with the mutational sites observed in the circulating variants. (1)

In preclinical studies, VIR-7831 achieved high concentration in the lungs, (1) the principal site of Covid-19 infection, (2) neutralized live virus, and was shown to engage effector functions, such as antibody-dependent cytotoxicity and phagocytosis, to mediate clearance of infected cells. (1)

The announcement of positive results from the COMET-ICE study follows a March 3, 2021, announcement by Vir and GSK that the Data and Safety Monitoring Board for the ACTIV-3 trial (NCT04501978) evaluating VIR-7831 in hospitalized adults with COVID-19 has recommended that the VIR-7831 arm of the trial be closed to enrolment while the data mature. No safety signals were reported, but the sensitivity analysis called into question the magnitude of the potential benefit of VIR-7831 administration to hospitalized patients. The National Institutes of Health is sponsoring the ACTIV-3 master protocol, which is examining the clinical safety and efficacy of numerous investigational agents relative to current standard of care therapy in hospitalized patients with more severe COVID-19.

Overall, the findings from the two clinical studies suggest that VIR-7831 could be of most benefit to patients during early onset of the disease, shortly after a positive test. This treatment has great potential to reduce both the severity of the disease in individuals and the substantial burden COVID-19 has placed on hospital staff and resources.

Another challenge, however, will be instilling confidence in doctors to prescribe anti-SARS-CoV-2 monoclonal therapies to patients. According to Dr. Derek Angus, an intensive-care physician at the University of Pittsburgh who spoke to Nature, (3) the absence of data published in peer-reviewed journals has left doctors wary. Moreover, high costs and more specialized requirements for administering infusion-based therapies will make what seems to be a working therapy and hope for patients a more complicated task. Intramuscular (IM) injection, which may substantially increase patient convenience, is possible. Clinical studies for anti-SARS-CoV-2 antibodies administered via intramuscular (IM) injection, including VIR-7831 (COMET-PEAK) and AZD7442 (PROVENT, STORM CHASER), are ongoing and clinical study results have not yet been announced.

1.       Cathcart et al. The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2. 2021. 
2.       Cevik et al. Virology, transmission, and pathogenesis of SARS-CoV-2. BMJ 2020; 371. BMJ. 2020. 
3.       Ledford H. COVID antibody treatments show promise for preventing severe disease. Nature 2021. 

Antibody Engineering & Therapeutics Europe Poster Competition

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Attention Student and Post-doc Members!

The Antibody Engineering & Therapeutics Europe Poster Competition is now open.

This virtual meeting will be held June 8-10, 2021.

To recognize the research activities of promising student and postdoctoral members, The Antibody Society is sponsoring a poster competition for these members in which two winners will be selected to receive:

  • Free registration to attend this virtual conference;
  • An opportunity to present a virtual poster during the conference; 
  • A Digital Badge as a Winner of the Poster Competition; and
  • The Antibody Society’s Award of Excellence (shown above).

In order to be considered for this poster competition, you must be a student or postdoctoral fellow member of The Antibody Society and your poster abstract must be submitted using the poster submission form. Please be sure to check the box on the poster submission form indicating that you want your abstract to be considered for the poster competition.

The Poster submission deadline is April 30, 2021.
Winners will be notified by May 7, 2021.

Submit your poster here!

Poster abstracts may be submitted and accepted for presentation at the conference after April 30th, but any submissions received after April 30 will not be considered for the poster competition.

Not a member? Please join!

Defying the “inevitable” development of type 1 diabetes

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Post written by Raquel Barroso Ferro, University of Aberdeen

Regular exogenous insulin injections, monitoring food and activity levels, increased risk of developing heart and kidney disease. These are some of the many challenges faced by people with type 1 diabetes (T1D), an autoimmune disease where the body’s own immune cells destroy its insulin-producing beta cells. This chronic condition affects over 540,000 children worldwide according to a leading UK charity, and is the second most common childhood disease in the US after asthma (1). Current estimates place a global increase in incidence of 2-5% every year (2), highlighting the increasing number of individuals having to physically, emotionally, and financially bear this burden and the need to develop therapeutics that can prevent, cure or improve the management of this condition.

Development of drugs that can delay the onset of T1D is ongoing. One such drug is teplizumab (hOKT3 γ1(Ala-Ala)), a humanized anti-CD3 monoclonal antibody that has been engineered to have reduced Fc receptor binding. Teplizumab works by modulating T cells, which are immune cells believed to be key players in the destruction of beta cells (3). Maintaining the remaining activity of the beta cells and enabling self-blood glucose control without the need for exogenous influence is critical to controlling the disease.

Results of a Phase 2 study (TrialNet TN10, NCT01030861) of teplizumab reported in 2019 were very promising (4). This randomized, blinded trial investigated if a single two-week course of treatment with teplizumab could delay or prevent the onset of T1D in high-risk individuals that were without a clinical diagnosis of T1D. The researchers observed that over the course of approximately 7 years (July 2011 to November 2018) teplizumab was able to delay the onset of T1D. Furthermore, this trial provided additional evidence of the importance of the T-cell mediated response for the onset of T1D, suggesting the value of using immunomodulation to affect disease development.

Sims et al. (5) extended the follow-up of participants in the original study, and have now reported that the effects persisted in the initial participants who received teplizumab. The median time to onset of T1D was more than double in participants who received teplizumab compared to those who received the placebo (~5 vs 2 years, respectively). Moreover, they observed improvements in beta cell function and, in some, a partial reversal in the decline of insulin secretion. Despite using a small cohort (total study enrolment = 76 participants) and a single 14-day course of drug, the results of this study form the foundation for exciting work in the future to actively prevent the onset of this lifelong condition whose prevalence only seems to be increasing.

A biologics license application for teplizumab for the delay or prevention of clinical T1D in at-risk individuals is undergoing priority review by the U.S. Food and Drug Administration, and their first action on the application is expected by July 2, 2021. The European Medicines Agency is evaluating a marketing authorization application for teplizumab.

References
1.       Menke et al. (2013). The prevalence of type 1 diabetes in the United States. Epidemiology 2013;24:773-774.
2.       Moobaseri et al. (2020).  Prevalence and incidence of type 1 diabetes in the world: a systematic review and meta-analysis. Health Promot Perspect. 2020; 10(2): 98–115. DOI: 10.34172/hpp.2020.18.
3.       Gaglia J, Kissler S. Anti-CD3 Antibody for the Prevention of Type 1 Diabetes: A Story of Perseverance. Biochemistry. 2019 Oct 8;58(40):4107-4111. doi: 10.1021/acs.biochem.9b00707.
4.       Herold et al. (2019). An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med 2019; 381:603-613. DOI:  10.1056/NEJMoa1902226.
5.       Sims et al. (2021).  Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Science Translational Medicine. 13 (583); eabc8980. DOI: 10.1126/scitranslmed.abc8980.

Interns looking for Integrated Immunology Projects

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The Friedrich Alexander University in Erlangen (Germany) is looking for PIs working in the AIRR-seq space to take on intern students. The internship should be a short scientific project spanning 8 weeks to 6 months. The application process starts in March and the internship is expected to start in October to December. You can read more information about it at  https://www.iimmune.nat.fau.de/ . 

Interested PIs should send an email to Simon Schäfer of the AIRR-C Communications Sub-committee (simon.schaefer@fau.de) for further details.

The Comms SC is interested in helping to facilitate matchmaking between PIs and students to engage in AIRR internship exchanges and this is the first step in that process.

Please add your name to the list today!