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You are here: Home / Archives for Coronavirus

Register for the AIRR-C COVID-19 Special Event!

August 17, 2020 by Pam Borghardt

Leveraging AIRR-sequencing data to inform the Biology of COVID-19

The AIRR Community is pleased to announce a 3-day special event focused on AIRR-sequencing data and COVID-19. Due to the unprecedented nature of the COVID-19 pandemic and the need for rapid scientific progress, this virtual meeting will provide recent analyses of the B- and T-cell receptor repertoires of COVID-19 patients. In addition, we will explore a key objective of the AIRR Community in the context of the pandemic: How the scientific response to the COVID-19 pandemic might be leveraged to promote the implementation of standards for AIRR-seq data.

Tuesday – Thursday, September 8th – 10th, 8:00 – 11:00 PDT / 11:00 AM – 2:00 PM EDT / 5:00 – 8:00 PM CEST

Full event details found here.

Register Now!!

Filed Under: AIRR Community, Coronavirus, COVID-19 Tagged With: Adaptive Immune Receptor Repertoire Community

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

July 13, 2020 by The Antibody Society

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.

 

Filed Under: Coronavirus, COVID-19, Vaccine Tagged With: COVID-19, SARS-CoV-2, Vaccine

Anti-SARS-CoV-2 REGN-COV2 enters clinical study

June 11, 2020 by Janice Reichert

On June 11, 2020, Regeneron Pharmaceuticals, Inc. announced the start of the first clinical trial of REGN-COV2 for the prevention and treatment of COVID-19. REGN-COV2 is a cocktail of the human antibodies REGN10933 and REGN10987, which were derived from Regeneron’s parallel efforts using both humanized VelocImmune® mice and blood samples from recovered COVID-19 patients to generate a large and diverse collection of antibodies targeting multiple different regions of the receptor-binding domain of the SARS-CoV-2 spike protein. Two papers describing the creation of REGN-COV2 and its anti-viral activity have been accepted for publication in Science.

The REGN-COV2 clinical program will consist of four separate study populations: hospitalized COVID-19 patients, non-hospitalized symptomatic COVID-19 patients, uninfected people in groups that are at high-risk of exposure and uninfected people with close exposure to a COVID-19 patient. The placebo-controlled trials will be conducted at multiple sites. The first two adaptive Phase 1/2/3 studies are evaluating REGN-COV2 as a treatment for hospitalized and non-hospitalized patients with COVID-19. The Phase 1 portion will focus on virologic and safety endpoints, and the Phase 2 portion will focus on virologic and clinical endpoints. Data from the Phase 1 and Phase 2 studies will be used to refine the endpoints and determine size for the Phase 3 studies.

REGN-COV2 is the 3rd anti-SARS-CoV-2 antibody-based drug to enter clinical study in the past 2 weeks. On June 1, 2020, Eli Lilly and Company announced LY-CoV555 had entered clinical study, and on June 7. 2020, Junshi Biosciences announced JS016 had entered clinical study.

Filed Under: Antibody therapeutic, Coronavirus, COVID-19 Tagged With: antibody therapeutics, COVID-19, SARS-CoV-2

AIRR Community Standards v1.3 and COVID-19 AIRR-Seq Data Available

June 10, 2020 by Pam Borghardt

The AIRR Community, a grassroots group of immunologists, immunogeneticists and computer scientists who are dedicated to developing protocols and standards to facilitate sharing of these data is pleased to announce the release of v1.3 of the AIRR Standards, including v1.0 of the AIRR Data Commons API (ADC API) to query AIRR compliant data repositories. The AIRR Community also notes that the first repositories in the AIRR Data Commons, based completely on AIRR Standards, are now in production, with the iReceptor Public Archive and VDJServer repositories early adopters of these AIRR Standards. With the release of v3.0 of the iReceptor Scientific Gateway, it is possible for researchers to query the AIRR Data Commons, greatly expanding the ability of researchers to find and analyze AIRR-seq data in support of biomedical research and improving patient care.

The AIRR Community is also pleased to announce the availability of the first COVID-19 AIRR-seq data sets in the AIRR Data Commons. The COVID-19 data is from the Nielsen et al. paper and is currently stored in the community based AIRR COVID-19 repository and is searchable through the iReceptor Scientific Gateway (gateway.ireceptor.org). More studies from COVID-19 patients will be added in the coming weeks. The AIRR Community is tracking and curating COVID-19 AIRR-seq papers and data sets, including their availability in the AIRR Data Commons, on the b-t.cr web site (https://b-t.cr/t/publicly-available-covid-19-airr-seq-data-sets).

Finally, the Research Data Alliance recently released its “guidelines and recommendations on data sharing in the context of COVID-19“. AIRR Community members Brian Corrie and Christian Busse participated in the preparation of this document, and in particular the authoring of the section around recommendations for sharing COVID-19 AIRR-seq data.

Filed Under: AIRR Community, Bioinformatics, Coronavirus, COVID-19 Tagged With: Adaptive Immune Receptor Repertoire Community

First anti-SARS-CoV2 antibody therapeutic enters clinical study

June 1, 2020 by Janice Reichert

On June 1, 2020, Eli Lilly and Company announced LY-CoV555, an anti-SARS-CoV2 IgG1 antibody,  has been administered to COVID-19 patients. LY-CoV555 is the first antibody specifically targeting SARS-COV-2 to enter clinical study.
The antibody was developed via a collaboration between Lilly and AbCellera. AbCellera,  with the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases, isolated single B cells from convalescent patients, identified a pool of ~500 candidate antibodies against the virus’ spike protein and selected leads from this pool. Lilly scientists further developed LY-CoV555 in just three months. The placebo-controlled study (J2W-MC-PYAA) will assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of LY-CoV555 following a single dose in patients hospitalized with COVID-19. Results are anticipated by the end of June 2020. The company intends to test LY-CoV555 and other neutralizing antibodies against SARS-CoV-2 over the next several months as monotherapy or antibody cocktails for  COVID-19.

As detailed in “Coronavirus in the crosshairs, Part 9“, more than 15 organizations have announced that their anti-SARS-CoV-2 molecules may enter clinical study during June to December 2020. The abundance of potential clinical candidates has enabled some organizations, including Eli Lilly and Company, Sorrento Therapeutics, Vir Biotechnology, Vanderbilt University Medical Center and Yumab, to engage in multiple partnerships, thereby allowing rapid development of multiple assets. Further information about other anti-SARS-CoV-2 antibodies that might enter clinical study soon can be found here.

Filed Under: Coronavirus, COVID-19 Tagged With: antibody discovery, COVID-19, SARS-CoV-2

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