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FDA issues Emergency Use Authorization for COVID-19 convalescent plasma

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On August 23, 2020, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for investigational COVID-19 convalescent plasma (CCP) for the treatment of COVID-19 in hospitalized patients. CCP is human plasma collected by FDA-registered blood establishments from individuals whose plasma contains anti SARS-CoV-2 antibodies, and who meet all donor eligibility requirements and are qualified. Titer levels of anti-SARS-CoV-2 antibodies are determined by the Ortho VITROS SARS-CoV-2 IgG test before units of CCP are released. Units found to have a signal-to-cutoff ratio of 12 or greater qualify as High Titer COVID-19 Convalescent Plasma.

Based on scientific evidence available, the FDA concluded CCP may be effective in treating COVID-19, and that the known and potential benefits of CCP outweigh the known and potential risks of the product. The EUA authorizes the distribution of COVID-19 convalescent plasma in the U.S. and its administration by health care providers, as appropriate, to treat suspected or laboratory-confirmed COVID-19 in hospitalized patients with COVID-19.

Data obtained from the ongoing National Convalescent Plasma Expanded Access Protocol (EAP) sponsored by the Mayo Clinic was included in FDA assessment. This uncontrolled, single-arm study was established in April 2020 to provide access to COVID-19 convalescent plasma in hospitalized subjects with severe or life-threatening COVID-19 or judged by the treating provider to be at high risk of progression to severe or life-threatening disease. As of August 13, 2020, over 90,000 patients have been enrolled. Data from the EAP posted online on August 12, 2020 reveals trends toward reduced mortality when patients receive CCP with higher antibody levels and at earlier time points. According to FDA’s decision memorandum:

  • In the subset of non-intubated patients, there was a 21% reduction in 7-day mortality (from 14% to 11%, p=0.03) in subjects transfused with high versus low titer CCP.
  • In the subgroup of patients less than 80 years of age who were not intubated and who were within 72 hours of diagnosis, a significant reduction in 7-day mortality from 11.3 to 6.3% (p = 0.0008) was observed when titers are binned to low versus high.
  • Survival trends observed at 7 days persisted over a longer time period, with significantly improved survival in non-intubated patients (p=0.032) and a larger benefit in the subset of patients not intubated at the time of treatment, less than 80 years of age, who were treated within 72 hours of diagnosis (p=0.0081)

However, there was no difference in 7-day survival in the overall population between subjects transfused with high versus low titer CCP, and there was no apparent association between neutralizing antibody titers and 7-day mortality in intubated subjects.

Information from the EUA and clinical studies of CCP may inform the development of other biologic COVID-19 interventions, such as recombinant anti-SARS-CoV-2 antibodies.  The Antibody Society is currently tracking 10 such antibodies in clinical studies or with clinical studies pending. We will report on the progress of these molecules and other COVID-19 interventions in the future.

SARS-CoV2, COVID-19 and the Cytokine Storm

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Written by Damani Bryant, Bio-Techne

The advent of a global pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has infected over 18 million people globally, as of August 2020. Of those infected, more than 700,000 people have been killed by coronavirus disease 2019 (COVID-19). Our current understanding is that the crisis began with several cases of pneumonia in Wuhan, China in early December 2019 (1). The World Health Organization (WHO) declared COVID-19 a public health emergency of international concern on January 30, 2020. COVID-19 was subsequently declared a pandemic by the WHO Director General on March 11. By August 2020, the WHO-documented distribution of COVID-19 infections is as follows: 9.9+ million cases in the Americas, 3+ million cases in Europe, 2+ million in South-East Asia, 1.5+ million cases in the Eastern Mediterranean, 800,000+ cases in Africa, and 300,000+ cases in the Western Pacific.

COVID-19 symptoms

Efforts to contain SARS-CoV2 are stymied by the fact that many of the infected are asymptomatic. One study estimates that up to 45% of those infected are asymptomatic (2). Symptomatic individuals have an onset between 2 and 14 days after exposure to the virus (3).  Relatively mild symptoms described by the  Centers for Disease Control (CDC) include: fever, chills, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headaches, loss of the sense of smell, sore throat, congestion or runny nose, nausea or vomiting and diarrhea. More severe responses to infection can progress from cytokine release syndrome (CRS), also known as the “cytokine storm”, to acute respiratory distress syndrome (ARDS), multiorgan failure, and death. CRS is thought to be an important step in the progression to ARDS in SARS-CoV2, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) infections (1,4). The clinical presentation of CRS ranges from mild fever, arthralgia, myalgia to high fever, uncontrolled systemic inflammatory responses, vascular leakage to disseminated intravascular coagulation and organ failure among other symptoms (5).  ARDS is formally defined as a respiratory failure within a week of a known insult that is characterized by bilateral opacities that are not fully explained by cardiac function or volume overload, effusion (fluid buildup), lung collapse, nodules and oxygenation below a specific threshold (6).  The death rate associated with ARDs is 40%.

Biology of SARS-CoV2 and COVID-19

SARS-CoV2 is a member of the Coronaviridae family, specifically the Coronavirinae subfamily that includes 4 genera: α-coronavirus, β-coronavirus, γ-coronavirus and δ-coronavirus (7). SARS-CoV2, SARS-COV and MERS-CoV are all RNA β coronaviruses. SARS-CoV2 shares 80% sequence identity with SARS-COV and 50% sequence identity with MERS-CoV (1,8). SARS-COV emerged from China in 2002 and spread globally, infecting over 8,000 and killing more than 700 people (8,9). MERS-CoV emerged from Saudi Arabia in 2012 and was responsible for over 2,000 infections and over 800 deaths globally (9). All three coronaviruses cause severe respiratory disease in humans. Although the SARS-CoV2 symptoms are milder and the mortality rate is thought to be lower (~3%-6.7%) than SARS-CoV (9.6%) and MERS-CoV (35%), it has a faster transmission rate in humans (7,8,10).

SARS-CoV2 and SARS-CoV enter cells via the angiotensin-converting enzyme-related carboxypeptidase (ACE2) receptor, which is expressed on cardiopulmonary and hematopoietic tissues. (1,11-13). SARS-CoV2 has been reported to have a 10-20 times higher binding affinity for ACE2 than SARS-CoV (7). Receptor-mediated viral entry requires priming of the S1 region of the viral spike (S) by the transmembrane serine protease 2 (TMPRSS2) (8,11,12). The S1 region of the viral spike binds to ACE2 followed by S2 subunit-mediated fusion of the viral and cellular membrane. After membrane fusion, ACE2 and SARS-CoV2 are endocytosed into the cell. SARS-CoV2 internalization has been correlated with increased production of proinflammatory cytokines such as nuclear factor kappa B (NF-κB) and interleukin 6 (IL-6) (8).  IL-6 signals through a cis signaling pathway and a trans signaling pathway (13). The cis signaling pathway involves the binding of IL-6 to a complex containing IL-6 receptor (IL-6R) and glycoprotein 130 (gp130). This stimulates the downstream activation of the Janus Kinase/Signal Transducer and Activator of Transcription 3 (JAK/STAT3) pathway. Activation of this pathway can promote CRS via activation of innate  and acquired immune mechanisms, including T cell differentiation and B cell activation and differentiation. In the trans signaling pathway, IL-6 forms a complex with soluble IL-6R and gp130 on many cell membranes due to the gp130’s ubiquitous expression. This propagates the CRS-stimulating signal to cells that do not express membrane IL-6R. Other cytokines and growth factors that are altered  in response to the trans signaling pathway include increased vascular endothelial growth factor (VEGF), monocyte chemoattractant protein 1 (MCP-1), IL-8, and decreased E-Cadherin in endothelial cells (13). As alluded to previously, CRS is characterized by the release of excessive amount of proinflammatory cytokines such as interferons, interleukins, chemokines, Colony stimulating factors, and tumor necrosis factor alpha, that are harmful to the host (8). Quantitative real time PCR studies of intensive care unit COVID-19 patients have documented elevated transcripts of a variety of cytokines including:  IL-2, IL-7, IL-10, G-CSF, IP-10,  MIP-1A, TNF  and CXCL-8 (14).

Methods for assessing the cytokine storm

A National Cancer Institute scale is commonly used to grade the severity of CRS in patients (5).  Other scales include: the Penn Grading Scale, Common Terminology Criteria for Adverse Events (CTCAE) v4.0, Lee et.al, 2014 and the MD Anderson Cancer Center (MDACC) scale (15). Grade 1 is characterized by fever. Symptoms are mild and not life threatening. Symptoms may or may not require treatment depending on the scale used. Grade 2 is characterized by hypotension that is responsive to fluids or low dose vasopressors. Symptoms are more moderate at this stage and may require hospitalization. All scales suggest an intervention. Organ toxicities may also be observed at this stage. Grade 3 is characterized by hypotension that requires high dose vasopressors, hypoxia and organ toxicities. Symptoms are more severe at this stage and require more aggressive interventions. Finally, grade 4 CRS is severe enough to require ventilation. CRS complications at this grade are life threatening.

Efficacy of COVID-19 therapeutic candidates

Circulating IL-6 has been correlated with COVID-19 severity in patients (16). Given the prominent role of IL-6, it is no surprise that tocilizumab, a human monoclonal anti-IL-6R antibody has been administered to patients with severe COVID-19 (17). Tocilizumab is approved for the treatment of CRS triggered by CAR T cell therapy by the Food and Drug Administration (13). Early data indicated that tocilizumab is associated with a shorter duration of vasomotor support and ventilation, shorter median time to recovery, improvement in CRS grade and computerized tomography imaging results in COVID-19 patients (17, 18). However, more recent data from Phase 3 clinical trials indicate that the human IL-6R antibodies tocilizumab and sarilumab are not associated with an overall benefit in COVID-19 patients. The Phase 3 sarilumab trial was recently halted because it failed to reach primary and secondary endpoints (19). A Phase 3 (global randomized, double blind, placebo controlled) tocilizumab trial was also halted because it failed to meet its primary endpoint of improved clinical status in patients hospitalized with severe COVID-19 pneumonia (20).

The corticosteroid dexamethasone, which is known for its anti-inflammatory and immunosuppressive effects, has recently been shown to reduce the mortality of COVID-19 patients on ventilators by one-third according to preliminary data presented to the WHO (21). Dexamethasone is now recommended standard of care for “patients with COVID-19 who are mechanically ventilated and in patients with COVID-19 who require supplemental oxygen but who are not mechanically ventilated” (22,23).  However, like tocilizumab, the anti-malarial drug hydroxychloroquine has fallen out of favor and clinical trials have been halted due to lack of efficacy (24).  As of mid-August 2020, there are over 3,000 COVID-19-related studies listed on the clinicaltrials.gov website, suggesting many other interventions are still being evaluated. Taken together, the rapid global transmission and high mortality rate of those infected underscores the urgent need to understand COVID’s mechanism of action and quickly pivot when a vaccine or therapeutic candidate is not efficacious.

References

  1. Coperchini, F. et al. (2020) The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 53:25
  2. Oran, D. P. and E. J. Topal (2020) Prevalence of Asymptomatic SARS-CoV-2 Infection A Narrative Review Ann Internal Med. [Epub ahead of print]
  3. Laur, S. A. et al. (2020) The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Ann Int Med. 172:577
  4. Channappanavar, R. and S. Perlman (2017) Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 39:529
  5. Shimabukuro-Vornhagen, A. et al. (2018) Cytokine release syndrome.  J. Immunotherapy of Cancer. 6:56
  6. Matthay, M. A. et al. (2019) Acute Respiratory Distress Syndrome. Nat. Rev. Disease Primers. 5:18
  7. Fani, M. et al. (2020) Comparison of the COVID-2019 (SARS-CoV-2) pathogenesis with SARS-CoV and MERS-CoV infections. Future Virol. [Epub ahead of print]
  8. Hirano, T and M. Murakami (2020) COVID-19: A New Virus, but a Familiar Receptor and Cytokine Release Syndrome. Immunity. 52:731
  9. Lu, R. et al. (2020) Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 395:565
  10. Perlman, S. (2020) Another Decade, Another Coronavirus. N Engl J Med. 382:760
  11. Zhou, P. et al. (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature [Epub ahead of print].
  12. Hoffmann, M. et al. (2020) SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell [Epub ahead of print]
  13. Moore, J. B. and C. H. June (2020) Cytokine release syndrome in severe COVID-19. Science 368:6490
  14. Huang, C. et al. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 395:497
  15. Liu, D. and J. Zhao (2018) Cytokine release syndrome: grading, modeling, and new therapy. J Hemat & Oncol. 11:121
  16. Ulhaq, Z. S. and G. V. Soraya (2020) Interleukin-6 as a potential biomarker of COVID-19 progression. Med Mal Infect. 50:382
  17. Kewan, T. et al. (2020) Tocilizumab for treatment of patients with severe COVID–19: A retrospective cohort study. E Clinical Med. [Epub ahead of print]
  18. Mastroianni, A. et al. (2020) Subcutaneous tocilizumab treatment in patients with severe COVID-19–related cytokine release syndrome: An observational cohort study. E Clinical Med. [Epub ahead of print]
  19. https://www.sanofi.com/en/media-room/press-releases/2020/2020-07-02-22-30-00
  20. https://www.roche.com/media/releases/med-cor-2020-07-29.htm
  21. https://www.who.int/news-room/detail/16-06-2020-who-welcomes-preliminary-results-about-dexamethasone-use-in-treating-critically-ill-covid-19-patients
  22. https://www.sciencemag.org/news/2020/07/one-uk-trial-transforming-covid-19-treatment-why-haven-t-others-delivered-more-results
  23. https://www.covid19treatmentguidelines.nih.gov/dexamethasone/
  24. https://www.who.int/news-room/detail/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19

Emergency Use Authorization requested for leronlimab

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On August 12, 2020, Cytodyn requested that the Food and Drug Administration grant an Emergency Use Authorization for leronlimab for mild to moderate COVID-19 based on data from the Phase 2 CD10 study (NCT04343651). In this study, patients were randomized to receive weekly doses of 700 mg leronlimab or placebo, both of which were administered via subcutaneous injection. Top-level results of the study showed that, in patients with Total Clinical Symptom Scores of ≥ 4 at baseline (higher scores equate to poorer health state), at Day 3, more subjects treated with leronlimab reported improvement in total clinical symptom score compared to the placebo group (90% on leronlimab arm vs. 71% on placebo). The EUA request was disclosed in an investment community conference call that will be available until September 12, 2020.

  • Leronlimab is a humanized IgG4 antibody targeting C-C chemokine receptor type 5.

Will SARS-CoV-2 introduce a new era for subunit vaccines?

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Written by: Gunnveig Grødeland, PhD, University of Oslo and Oslo University Hospital.

Effective control of Covid-19 is dependent upon development of protective and safe vaccines. At present, there are many different vaccine formats against SARS-CoV-2 in clinical development, with the more advanced already in clinical Phase III studies. A remaining challenge, however, is that we still do not have a clear understanding of what constitutes the most relevant type of immunity for protection against Covid-19, and what would be the best strategy for induction of such protection.

A serological survey of over 35,000 households in Spain has demonstrated that an overall 5% of the population has antibodies against SARS-CoV-2, with a higher prevalence of 10% around Madrid and lower in coastal areas (1). Spain has been one of the more severely Covid-19 affected countries in Europe. The fairly low incidence of antibodies in the Spanish population therefore implies that we cannot rely on herd immunity to develop naturally from the present pandemic. Further, the prevalence of SARS-CoV-2 specific antibodies in populations from the epicenters of New York and Lombardy has been estimated to be about 20-25% (2,3). It is not yet clear which antigens and epitopes the induced antibodies are directed against, but there are indications that the antibodies may have a limited capacity for neutralization (4).

During the previous SARS-CoV-1 outbreak in 2002/03, it was demonstrated that antibodies induced against immunodominant sites of the Spike protein were not neutralizing (5). It is also known that when neutralizing antibodies are induced they typically bind to the receptor binding domain of Spike, but also that such antibodies could potentially induce conformational changes in Spike due to mimicking of the ACE-2 receptor and as such potentially enhance viral infection (6). Careful design would therefore be needed for utilization of Spike as a vaccine antigen.

While most vaccines presently in development against SARS-CoV-2 aim for induction of antibodies, cellular immunity can also award protection against disease. Interestingly, a large part of the population have T cells that are reactive against different SARS-CoV-2 proteins even in the absence of a SARS-CoV-2 infection. These T cells are mostly CD4+, and likely originated from previous infections with the “common cold” coronaviruses (7,8). However, it is not yet clear to what degree their presence can reduce development of severe Covid-19 disease.

How should we proceed with vaccine development in a situation where the correlate of protection is not clear?

Pandemics may emerge when a novel pathogen has acquired the ability to transmit efficiently from human to human. As is the case for SARS-CoV-2, we should expect many unknowns when a new pandemic erupts. Vaccination remains the best preventive strategy, but how can one efficiently design vaccines when it is not clear what type of immune responses will be more important for protection? The only answer today is to simultaneously develop many different vaccine formats, compare their strengths and weaknesses, and select the best-fit candidate for vaccination of the population. For this to work, it is important that researchers share both promising and negative results for their particular vaccine format. It is my hope that this strategy will secure a vaccine ready to be large-scale deployed against SARS-CoV-2 during 2021.

We can be certain that SARS-CoV-2 will not be the last pandemic challenge facing the world. It is still unclear what will happen during this fall, but alongside taming the present outbreak, we should try to generate knowledge and strategies that may be of use for quenching the next pandemic emergence caused by an unknown pathogen X. This includes both strategies for managing transmission in society, development of treatment strategies that can be used for limiting replication across different viral families, as well as development of vaccine platforms that can be readily adapted for tailored induction of particular types of immunity.

A new era for subunit vaccines?

Interestingly, a majority of the vaccine formats presently in development against SARS-CoV-2 are subunit vaccines, meaning that they contain only selected viral antigens. At present, there are no genetic subunit vaccine licensed for use in humans, but there are a few protein based subunit vaccines available (e.g., Flublok by Sanofi, Recombivax by Merck).

Subunit vaccines have typically been hampered by reduced immunogenicity, necessitating the combined use of an adjuvant or alternative strategies for enhancing vaccine efficacy. However, their safety profiles and ease of production nevertheless makes subunit vaccines ideal for pandemic prevention.

The large amount of research presently going into development and clinical evaluation of different subunit vaccines is unprecedented. Thus, the ongoing SARS-CoV-2 pandemic may turn out to be the breaking point where subunit vaccines establish themselves as the preferred alternative to conventional inactivated or attenuated vaccines.

Subunit vaccines rely on rational selection and design of selected antigens. As such, immune responses can be steered towards antigenic regions more relevant for development of protective immunity. The better we understand human immunology, the better subunit vaccines we can design. For the future, we could be able to assign the relevant correlate of protection by examining shared pathogen traits, and then design vaccines specifically tailored for induction of the corresponding type of immunity. In the meantime, we will likely fare better by aiming a bit more broadly, and develop subunit vaccines that can induce both antibody and T cell responses.

References

1.    Pollan, M., B. Perez-Gomez, R. Pastor-Barriuso, J. Oteo, M. A. Hernan, M. Perez-Olmeda, J. L. Sanmartin, A. Fernandez-Garcia, I. Cruz, L. N. Fernandez de, M. Molina, F. Rodriguez-Cabrera, M. Martin, P. Merino-Amador, P. J. Leon, J. F. Munoz-Montalvo, F. Blanco, and R. Yotti. 2020. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. Lancet.

2.    Percivalle, E., G. Cambie, I. Cassaniti, E. V. Nepita, R. Maserati, A. Ferrari, M. R. Di, P. Isernia, F. Mojoli, R. Bruno, M. Tirani, D. Cereda, C. Nicora, M. Lombardo, and F. Baldanti. 2020. Prevalence of SARS-CoV-2 specific neutralising antibodies in blood donors from the Lodi Red Zone in Lombardy, Italy, as at 06 April 2020. Euro. Surveill 25.

3.    Stadlbauer D, Tan J, Jiang K, Hernandez M.M, Fabre S, Amanat F, Teo C, Arunkumar G, McMahon M, Jhang J, Nowak MD, Simon V, Sordillo EM, Bakel H, and Krammer F. 2020. Seroconversion of a city: Longitudinal monitoring of SARS-CoV-2 seroprevalence 1 in New York City. medRxiv preprint.

4.    Robbiani, D. F., C. Gaebler, F. Muecksch, J. C. C. Lorenzi, Z. Wang, A. Cho, M. Agudelo, C. O. Barnes, A. Gazumyan, S. Finkin, T. Hagglof, T. Y. Oliveira, C. Viant, A. Hurley, H. H. Hoffmann, K. G. Millard, R. G. Kost, M. Cipolla, K. Gordon, F. Bianchini, S. T. Chen, V. Ramos, R. Patel, J. Dizon, I. Shimeliovich, P. Mendoza, H. Hartweger, L. Nogueira, M. Pack, J. Horowitz, F. Schmidt, Y. Weisblum, E. Michailidis, A. W. Ashbrook, E. Waltari, J. E. Pak, K. E. Huey-Tubman, N. Koranda, P. R. Hoffman, A. P. West, Jr., C. M. Rice, T. Hatziioannou, P. J. Bjorkman, P. D. Bieniasz, M. Caskey, and M. C. Nussenzweig. 2020. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature.

5.    He, Y., Y. Zhou, H. Wu, B. Luo, J. Chen, W. Li, and S. Jiang. 2004. Identification of immunodominant sites on the spike protein of severe acute respiratory syndrome (SARS) coronavirus: implication for developing SARS diagnostics and vaccines. J. Immunol. 173: 4050-4057.

6.    Yang, Z. Y., H. C. Werner, W. P. Kong, K. Leung, E. Traggiai, A. Lanzavecchia, and G. J. Nabel. 2005. Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses. Proc. Natl. Acad. Sci. U. S. A 102: 797-801.

7.    Grifoni, A., D. Weiskopf, S. I. Ramirez, J. Mateus, J. M. Dan, C. R. Moderbacher, S. A. Rawlings, A. Sutherland, L. Premkumar, R. S. Jadi, D. Marrama, A. M. de Silva, A. Frazier, A. F. Carlin, J. A. Greenbaum, B. Peters, F. Krammer, D. M. Smith, S. Crotty, and A. Sette. 2020. Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell 181: 1489-1501.

8.    Le Bert N, Tan TA, Kunasegaran K, Tham CYL, Hafezi M, Chia A, Chng M, Lin M, Tan N, Linster M, Chia WN, Chen MIC, Wang LF, Ooi EE, Lalimuddin S, Tambyah PA, Low JGH, Tan YJ, and Bertoletti A. 2020. Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals. bioRxiv preprint.

 

COVID-19 data repository now available

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Interested in antibody/B-cell and T-cell receptor sequences derived from COVID-19 patients?

The iReceptor Project’s COVID-19 specific data repository has > 180 million sequences of AIRR-seq data (massive repertoires of antibody/B-cell and T-cell receptor sequences) from 5 studies of COVID-19 patients.

The data are available for download in a standard AIRR.tsv format, which makes it easy to import the data into many AIRR.seq analysis programs, and more COVID-19 studies will be available soon.

The iReceptor Gateway allows researchers to compare the COVID-19 data to ~2.5 billion immune receptor sequences from other infectious diseases, cancer studies, autoimmune patients and healthy control individuals. The Gateway can be used, for example, to determine whether antibodies discovered in COVID-19 patients are “public” (appearing in many individuals from many conditions including healthy controls) or “private” (only appearing in patients exhibiting severe COVID-19 reactions). This information and other repertoire comparisons should greatly accelerate the development of anti-COVID therapeutics and vaccines.

Present functionalities include:

  • Search for repertoires satisfying certain metadata (e.g. find all AIRR-seq repertoires from ovarian cancer studies)
  • Search for all repertoires that contain specific CDR3 sequences
  • Search identified repertoires for sequences derived from particular V, D, and J genes and alleles
  • Download sequences from these repertoires in AIRR.tsv format, easily importable to other AIRR-seq analysis tools

The iReceptor Gateway follows the protocols and standards developed by the AIRR-Community to facilitate sharing and analysis of AIRR-seq data. The AIRR Community, part of The Antibody Society, is a grassroots group of immunologists, immunogeneticists and computer scientists dedicated to sharing data through the AIRR Data Commons.  The iReceptor Project implements this Data Commons, and the development of the COVID-specific repository on the iReceptor Gateway follows the call from the AIRR Community for increased sharing of data during the coronavirus crisis.

Researchers interested in sharing data or exploring the AIRR Data Commons through the open iReceptor Gateway should visit www.ireceptor.org and contact support@ireceptor.org for an account.

iReceptor is a member of the iReceptor Plus Consortium.