Special Issue "Antibodies, B Cell Responses and Immune Responses to SARS-CoV-2 Infections"

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (20 March 2022) | Viewed by 26998

Special Issue Editors

Prof. Dr. Luis Martinez-Sobrido
E-Mail Website
Guest Editor
1. Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14625, USA
2. Texas Biomedical Research Institute, San Antonio, TX 78245, USA
Interests: virology; vaccines; antivirals; influenza viruses; arenaviruses; Zika virus; coronavirus; SARS-CoV-2; COVID-19; innate immunity; adaptive immunity; interferon; virus-host interactions
Special Issues, Collections and Topics in MDPI journals
Prof. James J. Kobie
E-Mail Website
Guest Editor
Infectious Diseases Division, University of Rochester, Rochester, NY, USA
Interests: B cells; antibodies; viruses

Special Issue Information

Dear Colleagues,

Coronaviruses (CoVs) are enveloped, single-stranded, positive-sense RNA viruses responsible for seasonal mild respiratory illness in humans. They include endemic human CoV NL63, 229E, OC43, and HKU1, which are associated with a small proportion of these mild respiratory illnesses. However, three CoVs are most notable as human respiratory pathogens that have caused significant morbidity and mortality. These are Severe Acute Respiratory Syndrome CoV-1 (SARS-CoV-1), which spread in 2003, Middle East Respiratory Syndrome CoV (MERS-CoV), appeared in 2012 and still present, and Severe Acute Respiratory Syndrome CoV-2 (SARS-CoV-2), which is responsible for coronavirus disease 2019 (COVID-19). COVID-19 emerged in the city of Wuhan, China, in December 2019 and has now caused a world-wide pandemic, dramatically impacting public health and socioeconomic activities across the world. The explosive emergence of SARS-CoV-2 infection in humans has resulted in a pandemic of COVID-19 with an alarming case fatality, posing a threat to human health and economy of an unprecedent magnitude, rivaling the “Spanish flu” pandemic of 1918–1919. To date, no United States Food and Drug Administration (FDA)-approved vaccines and/or specific antivirals are available for the treatment of SARS-CoV-2 infection and COVID-19 in humans, which has triggered vast scientific efforts to develop countermeasures to deal with this infection.

Although experimental treatments for COVID-19 infection are being tested clinically, and the development of preventative vaccines is ongoing, there does not yet exist a highly specific, scalable, and sustainable approved therapeutic. Monoclonal antibodies (mAbs) are a growing class of drugs, in part due to their high degree of specificity, limited off-target effects, and superb safety profile. In addition to their use in the treatment of cancer and autoimmunity, several mAbs are already licensed or in clinical trials for the treatment and prevention of various infectious diseases (e.g., Palivizumab for Respiratory Syncytial Virus and Zmapp for Ebola virus). However, numerous fundamental aspects of the host B cells and antibody response to infection remain to be resolved. Foremost, does infection result in protective humoral immunity? If so, how long is it maintained, and will it be sufficiently broad to protect from emerging antigenic variations in SARS-CoV-2?

In this Special Issue “Antibodies, B Cell Responses and Immune Responses to SARS-CoV-2 Infections", we aim to cover all aspects related to vaccinology, such as traditional and new approaches for COVID-19 vaccine development, vaccine immunogenicity and protection efficacy, classical and new antigen targeting, conserved viral antigens and their epitopes, identification and characterization of SARS-CoV-2 cross-reactive and broadly neutralizing mAbs, including therapeutic and prophylactic mAbs, induction of efficient and protective adaptive B cell responses, correlation of mAb and B cell activation to protection against SARS-CoV-2, and currently available and new animal models of SARS-CoV-2 vaccine testing. This Special Issue will also aim to examine classical and new vaccine methodologies for the control of SARS-CoV-2 infections. We hope that the collection of novel research and review manuscripts in this Special Issue will provide researchers with information on the latest and newest discoveries to help them reach the goal of developing and implementing treatment options for the control of SARS-CoV-2 infection, which is a priority for the treatment of COVID-19.

Prof. Dr. Luis Martinez-Sobrido 
Prof. James J. Kobie
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibodies is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Antibodies
  • B Cell Responses
  • Immune Responses
  • COVID-19
  • SARS-CoV-2 Infections
  • mAbs
  • Monoclonal antibodies
  • vaccine development

Published Papers (10 papers)

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Research

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Article
MALDI-TOF-MS-Based Identification of Monoclonal Murine Anti-SARS-CoV-2 Antibodies within One Hour
Antibodies 2022, 11(2), 27; https://0-doi-org.brum.beds.ac.uk/10.3390/antib11020027 - 14 Apr 2022
Viewed by 635
Abstract
During the SARS-CoV-2 pandemic, many virus-binding monoclonal antibodies have been developed for clinical and diagnostic purposes. This underlines the importance of antibodies as universal bioanalytical reagents. However, little attention is given to the reproducibility crisis that scientific studies are still facing to date. [...] Read more.
During the SARS-CoV-2 pandemic, many virus-binding monoclonal antibodies have been developed for clinical and diagnostic purposes. This underlines the importance of antibodies as universal bioanalytical reagents. However, little attention is given to the reproducibility crisis that scientific studies are still facing to date. In a recent study, not even half of all research antibodies mentioned in publications could be identified at all. This should spark more efforts in the search for practical solutions for the traceability of antibodies. For this purpose, we used 35 monoclonal antibodies against SARS-CoV-2 to demonstrate how sequence-independent antibody identification can be achieved by simple means applied to the protein. First, we examined the intact and light chain masses of the antibodies relative to the reference material NIST-mAb 8671. Already half of the antibodies could be identified based solely on these two parameters. In addition, we developed two complementary peptide mass fingerprinting methods with MALDI-TOF-MS that can be performed in 60 min and had a combined sequence coverage of over 80%. One method is based on the partial acidic hydrolysis of the protein by 5 mM of sulfuric acid at 99 °C. Furthermore, we established a fast way for a tryptic digest without an alkylation step. We were able to show that the distinction of clones is possible simply by a brief visual comparison of the mass spectra. In this work, two clones originating from the same immunization gave the same fingerprints. Later, a hybridoma sequencing confirmed the sequence identity of these sister clones. In order to automate the spectral comparison for larger libraries of antibodies, we developed the online software ABID 2.0. This open-source software determines the number of matching peptides in the fingerprint spectra. We propose that publications and other documents critically relying on monoclonal antibodies with unknown amino acid sequences should include at least one antibody fingerprint. By fingerprinting an antibody in question, its identity can be confirmed by comparison with a library spectrum at any time and context. Full article
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Article
Fc-Independent Protection from SARS-CoV-2 Infection by Recombinant Human Monoclonal Antibodies
Antibodies 2021, 10(4), 45; https://0-doi-org.brum.beds.ac.uk/10.3390/antib10040045 - 08 Nov 2021
Cited by 2 | Viewed by 1404
Abstract
The use of passively-administered neutralizing antibodies is a promising approach for the prevention and treatment of SARS-CoV-2 infection. Antibody-mediated protection may involve immune system recruitment through Fc-dependent activation of effector cells and the complement system. However, the role of Fc-mediated functions in the [...] Read more.
The use of passively-administered neutralizing antibodies is a promising approach for the prevention and treatment of SARS-CoV-2 infection. Antibody-mediated protection may involve immune system recruitment through Fc-dependent activation of effector cells and the complement system. However, the role of Fc-mediated functions in the efficacious in-vivo neutralization of SARS-CoV-2 is not yet clear, and it is of high importance to delineate the role this process plays in antibody-mediated protection. Toward this aim, we have chosen two highly potent SARS-CoV-2 neutralizing human monoclonal antibodies, MD65 and BLN1 that target distinct domains of the spike (RBD and NTD, respectively). The Fc of these antibodies was engineered to include the triple mutation N297G/S298G/T299A that eliminates glycosylation and the binding to FcγR and to the complement system activator C1q. As expected, the virus neutralization activity (in-vitro) of the engineered antibodies was retained. To study the role of Fc-mediated functions, the protective activity of these antibodies was tested against lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice, when treatment was initiated either before or two days post-exposure. Antibody treatment with both Fc-variants similarly rescued the mice from death reduced viral load and prevented signs of morbidity. Taken together, this work provides important insight regarding the contribution of Fc-effector functions in MD65 and BLN1 antibody-mediated protection, which should aid in the future design of effective antibody-based therapies. Full article
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Article
From Anti-SARS-CoV-2 Immune Response to the Cytokine Storm via Molecular Mimicry
Antibodies 2021, 10(4), 36; https://0-doi-org.brum.beds.ac.uk/10.3390/antib10040036 - 24 Sep 2021
Cited by 4 | Viewed by 2337
Abstract
The aim of this study was to investigate the role of molecular mimicry in the cytokine storms associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human proteins endowed with anti-inflammatory activity were assembled and analyzed for peptide sharing with the SARS-CoV-2 spike [...] Read more.
The aim of this study was to investigate the role of molecular mimicry in the cytokine storms associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human proteins endowed with anti-inflammatory activity were assembled and analyzed for peptide sharing with the SARS-CoV-2 spike glycoprotein (gp) using public databases. It was found that the SARS-CoV-2 spike gp shares numerous pentapeptides with anti-inflammatory proteins that, when altered, can lead to cytokine storms characterized by diverse disorders such as systemic multiorgan hyperinflammation, macrophage activation syndrome, ferritinemia, endothelial dysfunction, and acute respiratory syndrome. Immunologically, many shared peptides are part of experimentally validated epitopes and are also present in pathogens to which individuals may have been exposed following infections or vaccinal routes and of which the immune system has stored memory. Such an immunologic imprint might trigger powerful anamnestic secondary cross-reactive responses, thus explaining the raging of the cytokine storm that can occur following exposure to SARS-CoV-2. In conclusion, the results support molecular mimicry and the consequent cross-reactivity as a potential mechanism in SARS-CoV-2-induced cytokine storms, and highlight the role of immunological imprinting in determining high-affinity, high-avidity, autoimmune cross-reactions as a pathogenic sequela associated with anti-SARS-CoV-2 vaccines. Full article
Article
Viroinformatics-Based Analysis of SARS-CoV-2 Core Proteins for Potential Therapeutic Targets
Antibodies 2021, 10(1), 3; https://0-doi-org.brum.beds.ac.uk/10.3390/antib10010003 - 11 Jan 2021
Cited by 3 | Viewed by 4042
Abstract
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus for which no known effective antiviral drugs are available. In the present study, to accelerate the discovery of potential drug candidates, bioinformatics-based in silico drug discovery approaches are utilized. We performed multiple [...] Read more.
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus for which no known effective antiviral drugs are available. In the present study, to accelerate the discovery of potential drug candidates, bioinformatics-based in silico drug discovery approaches are utilized. We performed multiple sequence alignments of the Spike (S) protein with 75 sequences of different viruses from the Orthocoronavirinae subfamily. This provided us with insights into the evolutionarily conserved domains that can be targeted using drugs or specific antibodies. Further, we analyzed the mechanism of SARS-CoV-2 core proteins, i.e., S and RdRp (RNA-dependent RNA polymerase), to elucidate how the virus infection can utilize hemoglobin to decrease the blood oxygen level. Moreover, after a comprehensive literature survey, more than 60 antiviral drugs were chosen. The candidate drugs were then ranked based on their potential to interact with the Spike and RdRp proteins of SARS-CoV-2. The present multidimensional study further advances our understanding of the novel viral molecular targets and potential of computational approaches for therapeutic assessments. The present study can be a steppingstone in the selection of potential drug candidates to be used either as a treatment or as a reference point when designing a new drug/antibody/inhibitory peptide/vaccine against SARS-CoV-2. Full article
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Article
From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry
Antibodies 2020, 9(3), 33; https://0-doi-org.brum.beds.ac.uk/10.3390/antib9030033 - 16 Jul 2020
Cited by 38 | Viewed by 6849
Abstract
Aim: To define the autoimmune potential of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods: Experimentally validated epitopes cataloged at the Immune Epitope DataBase (IEDB) and present in SARS-CoV-2 were analyzed for peptide sharing with the human proteome. Results: Immunoreactive epitopes present [...] Read more.
Aim: To define the autoimmune potential of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods: Experimentally validated epitopes cataloged at the Immune Epitope DataBase (IEDB) and present in SARS-CoV-2 were analyzed for peptide sharing with the human proteome. Results: Immunoreactive epitopes present in SARS-CoV-2 were mostly composed of peptide sequences present in human proteins that—when altered, mutated, deficient or, however, improperly functioning—may associate with a wide range of disorders, from respiratory distress to multiple organ failure. Conclusions: This study represents a starting point or hint for future scientific–clinical investigations and suggests a range of possible protein targets of autoimmunity in SARS-CoV-2 infection. From an experimental perspective, the results warrant the testing of patients’ sera for autoantibodies against these protein targets. Clinically, the results warrant a stringent surveillance on the future pathologic sequelae of the current SARS-CoV-2 pandemic. Full article
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Review

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Review
Long-Term Immunity and Antibody Response: Challenges for Developing Efficient COVID-19 Vaccines
Antibodies 2022, 11(2), 35; https://0-doi-org.brum.beds.ac.uk/10.3390/antib11020035 - 12 May 2022
Viewed by 227
Abstract
Questions and concerns regarding the efficacy and immunogenicity of coronavirus disease 2019 (COVID-19) vaccines have plagued scientists since the BNT162b2 mRNA vaccine was introduced in late 2020. As a result, decisions about vaccine boosters based on breakthrough infection rates and the decline of [...] Read more.
Questions and concerns regarding the efficacy and immunogenicity of coronavirus disease 2019 (COVID-19) vaccines have plagued scientists since the BNT162b2 mRNA vaccine was introduced in late 2020. As a result, decisions about vaccine boosters based on breakthrough infection rates and the decline of antibody titers have commanded worldwide attention and research. COVID-19 patients have displayed continued severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-spike-protein-specific antibodies and neutralizing antibodies in longitudinal studies; in addition, cytokine activation has been detected at early steps following SARS-CoV-2 infection. Epitopes that are highly reactive and can mediate long-term antibody responses have been identified at the spike and ORF1ab proteins. The N-terminal domain of the S1 and S2 subunits is the location of important SARS-CoV-2 spike protein epitopes. High sequence identity between earlier and newer variants of SARS-CoV-2 and different degrees of sequence homology among endemic human coronaviruses have been observed. Understanding the extent and duration of protective immunity is consequential for determining the course of the COVID-19 pandemic. Further knowledge of memory responses to different variants of SARS-CoV-2 is needed to improve the design of the vaccine. Full article
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Review
Cellular, Antibody and Cytokine Pathways in Children with Acute SARS-CoV-2 Infection and MIS-C—Can We Match the Puzzle?
Antibodies 2022, 11(2), 25; https://0-doi-org.brum.beds.ac.uk/10.3390/antib11020025 - 01 Apr 2022
Viewed by 798
Abstract
The newly identified strain of the Coronaviridae family called severe acute respiratory syndrome (SARS-CoV-2) recently became the most significant health threat for adults and children. Some main predictors of severe clinical course in patients with SARS-CoV-2 infection are age and concomitant health conditions. [...] Read more.
The newly identified strain of the Coronaviridae family called severe acute respiratory syndrome (SARS-CoV-2) recently became the most significant health threat for adults and children. Some main predictors of severe clinical course in patients with SARS-CoV-2 infection are age and concomitant health conditions. Therefore, the proper evaluation of SARS-CoV-2-specific immunity is urgently required to understand and predict the spectrum of possible clinical phenotypes and recommend vaccination options and regimens in children. Furthermore, it is critical to characterize the nature of SARS-CoV-2-specific immune responses in children following asymptomatic infection and COVID-19 and other related conditions such as multisystem inflammatory syndrome (MIS-C), para-infectious and late postinfectious consequences. Recent studies involving children revealed a variety of cytokines, T cells and antibody responses in the pathogenesis of the disease. Moreover, different clinical scenarios in children were observed-asymptomatic seroprevalence, acute SARS-CoV-2 infection, and rarely severe COVID-19 with typical cytokine storm, MIS-C, long COVID-19, etc. Therefore, to gain a better clinical view, adequate diagnostic criteria and treatment algorithms, it is essential to create a realistic picture of the immunological puzzle of SARS-CoV-2 infection in different age groups. Finally, it was demonstrated that children may exert a potent and prolonged adaptive anti-SARS-CoV-2 immune response, with significant cross-reactions against other human Corona Viruses, that might contribute to disease sparing effect in this age range. However, the immunopathology of the virus has to be elucidated first. Full article
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Review
Structural Features and PF4 Functions that Occur in Heparin-Induced Thrombocytopenia (HIT) Complicated by COVID-19
Antibodies 2020, 9(4), 52; https://0-doi-org.brum.beds.ac.uk/10.3390/antib9040052 - 10 Oct 2020
Cited by 15 | Viewed by 3275
Abstract
Platelet factor 4 (PF4, CXCL4) is a small chemokine protein released by activated platelets. Although a major physiological function of PF4 is to promote blood coagulation, this cytokine is involved in innate and adaptive immunity in events when platelets are activated in response [...] Read more.
Platelet factor 4 (PF4, CXCL4) is a small chemokine protein released by activated platelets. Although a major physiological function of PF4 is to promote blood coagulation, this cytokine is involved in innate and adaptive immunity in events when platelets are activated in response to infections. Coronavirus disease 2019 (COVID-19) patients have abnormal coagulation activities, and severe patients develop higher D-dimer levels. D-dimers are small protein products present in the blood after blood clots are degraded by fibrinolysis. To prevent clotting, heparin is often clinically used in COVID-19 patients. Some clinical procedures for the management of COVID-19 patients may include extracorporeal membrane oxygenation (ECMO) and renal replacement therapy (CRRT), which also require the use of heparin. Anti-PF4 antibodies are frequently detected in severe patients and heparin-induced thrombocytopenia (HIT) can also be observed. PF4 and its role in HIT as well as in pathologies seen in COVID-19 patients define a potential therapeutic option of using blocking antibodies in the treatment of COVID-19. Full article
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Other

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Case Report
The Course of SARS-COV2 Infection Was Not Severe in a Crohn’s Patient Who Administered Maintenance Anti-TNF Therapy Overlapping the Early Pre-Symptomatic Period of Infection
Antibodies 2020, 9(3), 42; https://0-doi-org.brum.beds.ac.uk/10.3390/antib9030042 - 15 Aug 2020
Cited by 7 | Viewed by 2955
Abstract
The Inflammatory Bowel Disease (IBD) population, which may require treatment with immunosuppressive medications, may be uniquely vulnerable to COVID-19 infection. In fact, there is some evidence these medications may inhibit the cytokine storm that is theorized to cause a rapid decline seen in [...] Read more.
The Inflammatory Bowel Disease (IBD) population, which may require treatment with immunosuppressive medications, may be uniquely vulnerable to COVID-19 infection. In fact, there is some evidence these medications may inhibit the cytokine storm that is theorized to cause a rapid decline seen in COVID-19. In addition, the digestive symptoms of COVID-19 can be difficult to distinguish from the activation of IBD. We present an interesting case of a Crohn’s patient inadvertently administering anti-cytokine therapy during the pre-symptomatic period of COVID-19 infection. Immune suppression during early infection with SARS-COV2 risks a poor immune response to the virus and could theoretically result in a more severe course of infection. Full article
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Perspective
Is the Host Viral Response and the Immunogenicity of Vaccines Altered in Pregnancy?
Antibodies 2020, 9(3), 38; https://0-doi-org.brum.beds.ac.uk/10.3390/antib9030038 - 04 Aug 2020
Cited by 5 | Viewed by 3420
Abstract
The intricacy of the maternal immune system arises from its ability to prevent a maternal immune response against a semi-allogenic fetus, while protecting the mother against harmful pathogens. However, these immunological adaptations may also make pregnant women vulnerable to developing adverse complications from [...] Read more.
The intricacy of the maternal immune system arises from its ability to prevent a maternal immune response against a semi-allogenic fetus, while protecting the mother against harmful pathogens. However, these immunological adaptations may also make pregnant women vulnerable to developing adverse complications from respiratory viral infections. While the influenza and SARS pandemics support this theory, there is less certainty regarding the clinical impact of SARS-CoV-2 in pregnancy. In the current COVID-19 pandemic, vaccine development is key to public preventative strategies. Whilst most viral vaccines are able to induce a seroprotective antibody response, in some high-risk individuals this may not correlate with clinical protection. Some studies have shown that factors such as age, gender, and chronic illnesses can reduce their effectiveness and in this review, we discuss how pregnancy may affect the efficacy and immunogenicity of vaccines. We present literature to support the hypothesis that pregnant women are more susceptible to respiratory viral infections and may not respond to vaccines as effectively. In particular, we focus on the clinical implications of important respiratory viral infections such as influenza during pregnancy, and the pregnancy induced alterations in important leukocytes such as TFH, cTFH and B cells, which play an important role in generating long-lasting and high-affinity antibodies. Finally, we review how this may affect the efficacy of vaccines against influenza in pregnancy and highlight areas that require further research. Full article
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