Antibodies and B Cell Memory in Viral Immunity

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 30847

Special Issue Editors


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Guest Editor
Cellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, USA
Interests: generation of MHC class I peptide ligands from defective ribosomal products (DRiPs) and other endogenous antigens; cell biology of specialized and non-canonical protein translation; defining mechanisms of influenza A virus evolution and antigenic variation in viral glycoproteins; understanding immunodominance in B-cell and antibody responses to influenza A virus

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Guest Editor
Institutionen för biomedicin, Göteborgs universitet, Gothenburg, Sweden
Interests: antibody; B cell; immunodominance; influenza; viral immunity; immune memory; humoral immunity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The aim of this Special Issue is to present focused reviews on recent advances in understanding:

  • The basic immunobiology responsible for primary and memory B cell and antibody responses to acute viral infections;
    • Contributions of various immune cell types in classical germinal center response and extrafollicular response;
  • The diversity and immunodominance of antiviral antibody responses;
  • How antibodies exert antiviral activity in vivo;
    • Direct effects and contributions of Fc expressing innate immune cells;
  • How antibody selection contributes to viral evolution;
  • Viral interference with B cell immunity;
  • Computational modeling of Ab responses.

Dr. Jonathan Wilson Yewdell
Dr. Davide Angeletti
Guest Editors

Manuscript Submission Information

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Keywords

  • antibodies
  • antibody immunodominance
  • B cells
  • memory B cells
  • follicular dendritic cells
  • follicular T helper cells
  • germinal center
  • humoral immunity
  • influenza virus
  • SARS-CoV2
  • viral evolution

Published Papers (7 papers)

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Research

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15 pages, 2115 KiB  
Article
Persistence of Naturally Acquired and Functional SARS-CoV-2 Antibodies in Blood Donors One Year after Infection
by Verena Nunhofer, Lisa Weidner, Alexandra Domnica Hoeggerl, Georg Zimmermann, Natalie Badstuber, Christoph Grabmer, Christof Jungbauer, Nadja Lindlbauer, Nina Held, Monica Pascariuc, Tuulia Ortner, Eva Rohde and Sandra Laner-Plamberger
Viruses 2022, 14(3), 637; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030637 - 18 Mar 2022
Cited by 10 | Viewed by 2536
Abstract
The developmental course of antibodies produced after a SARS-CoV-2 infection has been insufficiently investigated so far. Therefore, the aim of this study was to investigate the dynamics of SARS-CoV-2 antibody levels against the viral nucleocapsid- and spike-protein among Austrian blood donors as a [...] Read more.
The developmental course of antibodies produced after a SARS-CoV-2 infection has been insufficiently investigated so far. Therefore, the aim of this study was to investigate the dynamics of SARS-CoV-2 antibody levels against the viral nucleocapsid- and spike-protein among Austrian blood donors as a representative group of a supposedly healthy population within the first year after a SARS-CoV-2 infection. The impact of age, sex, vaccination status, AB0-blood group and awareness about the infection was evaluated. Our study shows that the level of anti-N antibodies is declining, while anti-S antibody levels remain stable. Antibodies detected were functional in vitro. Age, sex and blood group do not influence antibody dynamics. However, blood group AB shows significantly lower antibody levels and in vitro functionality compared to other blood groups. Our data reveal that one out of five individuals was not aware of a previous SARS-CoV-2 infection and that the disease course neither affects the level of antibody production nor the in vitro functionality. We also found that 14% of participants show persisting COVID-19-related symptoms for up to nine months. Our results provide valuable insights into the dynamics of the immune response after a SARS-CoV-2 infection in a representative cohort of adult blood donors in Central Europe. Full article
(This article belongs to the Special Issue Antibodies and B Cell Memory in Viral Immunity)
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18 pages, 4319 KiB  
Article
Structure Based Affinity Maturation and Characterizing of SARS-CoV Antibody CR3022 against SARS-CoV-2 by Computational and Experimental Approaches
by Wei Yu, Nan Zhong, Xin Li, Jiayi Ren, Yueming Wang, Chengming Li, Gui Yao, Rui Zhu, Xiaoli Wang, Zhenxing Jia, Changwen Wu, Rongfeng Chen, Weihong Zheng, Huaxin Liao, Xiaomin Wu and Xiaohui Yuan
Viruses 2022, 14(2), 186; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020186 - 19 Jan 2022
Cited by 5 | Viewed by 2341
Abstract
The COVID-19 epidemic is raging around the world. Neutralizing antibodies are powerful tools for the prevention and treatment of SARS-CoV-2 infection. Antibody CR3022, a SARS-CoV neutralizing antibody, was found to cross-react with SARS-CoV-2, but its affinity was lower than that of its binding [...] Read more.
The COVID-19 epidemic is raging around the world. Neutralizing antibodies are powerful tools for the prevention and treatment of SARS-CoV-2 infection. Antibody CR3022, a SARS-CoV neutralizing antibody, was found to cross-react with SARS-CoV-2, but its affinity was lower than that of its binding with SARS-CoV, which greatly limited the further development of CR3022 against SARS-CoV-2. Therefore, it is necessary to improve its affinity to SARS-CoV-2 in vitro. In this study, the structure-based molecular simulations were utilized to virtually mutate the possible key residues in the complementarity-determining regions (CDRs) of the CR3022 antibody. According to the criteria of mutation energy, the mutation sites that have the potential to impact the antibody affinity were then selected. Then optimized CR3022 mutants with the enhanced affinity were further identified and verified by enzyme-linked immunosorbent assay (ELISA), surface plasma resonance (SPR) and autoimmune reactivity experiments. Finally, molecular dynamics (MD) simulation and binding free energy calculation (MM/PBSA) were performed on the wild-type CR3022 and its two double-site mutants to understand in more detail the contribution of these sites to the higher affinity. It was found that the binding affinity of the CR3022 antibody could be significantly enhanced more than ten times after the introduction of the S103F/Y mutation in HCDR–3 and the S33R mutation in LCDR–1. The additional hydrogen-bonding, hydrophobic interactions, as well as salt-bridges formed between the modified double-site mutated antibody and SARS-CoV-2 RBD were identified. The computational and experimental results clearly demonstrated that the affinity of the modified antibody has been greatly enhanced. This study indicates that CR3022 as a neutralizing antibody recognizing the conserved region of RBD against SARS-CoV with cross-reactivity with SARS-CoV-2, a different member in a large family of coronaviruses, could be improved by the computational and experimental approaches which provided insights for developing antibody drugs against SARS-CoV-2. Full article
(This article belongs to the Special Issue Antibodies and B Cell Memory in Viral Immunity)
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16 pages, 1574 KiB  
Article
Peripheral Blood Immune Profiling of Convalescent Plasma Donors Reveals Alterations in Specific Immune Subpopulations Even at 2 Months Post SARS-CoV-2 Infection
by Nikolaos Orologas-Stavrou, Marianna Politou, Pantelis Rousakis, Ioannis V. Kostopoulos, Ioannis Ntanasis-Stathopoulos, Edison Jahaj, Eleni Tsiligkeridou, Maria Gavriatopoulou, Efstathios Kastritis, Anastasia Kotanidou, Meletios-Athanasios Dimopoulos, Ourania E. Tsitsilonis and Evangelos Terpos
Viruses 2021, 13(1), 26; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010026 - 25 Dec 2020
Cited by 22 | Viewed by 4295
Abstract
Immune profiling of patients with COVID-19 has shown that SARS-CoV-2 causes severe lymphocyte deficiencies (e.g., lymphopenia, decreased numbers, and exhaustion of T cells) and increased levels of pro-inflammatory monocytes. Peripheral blood (PB) samples from convalescent plasma (CP) donors, COVID-19 patients, and control subjects [...] Read more.
Immune profiling of patients with COVID-19 has shown that SARS-CoV-2 causes severe lymphocyte deficiencies (e.g., lymphopenia, decreased numbers, and exhaustion of T cells) and increased levels of pro-inflammatory monocytes. Peripheral blood (PB) samples from convalescent plasma (CP) donors, COVID-19 patients, and control subjects were analyzed by multiparametric flow cytometry, allowing the identification of a wide panel of immune cells, comprising lymphocytes (T, B, natural killer (NK) and NKT cells), monocytes, granulocytes, and their subsets. Compared to active COVID-19 patients, our results revealed that the immune profile of recovered donors was restored for most subpopulations. Nevertheless, even 2 months after recovery, CP donors still had reduced levels of CD4+ T and B cells, as well as granulocytes. CP donors with non-detectable levels of anti-SARS-CoV-2-specific antibodies in their serum were characterized by higher Th9 and Th17 cells, which were possibly expanded at the expense of Th2 humoral immunity. The most noticeable alterations were identified in previously hospitalized CP donors, who presented the lowest levels of CD8+ regulatory T cells, the highest levels of CD56+CD16 NKT cells, and a promotion of a Th17-type phenotype, which might be associated with a prolonged pro-inflammatory response. A longer follow-up of CP donors will eventually reveal the time needed for full recovery of their immune system competence. Full article
(This article belongs to the Special Issue Antibodies and B Cell Memory in Viral Immunity)
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Review

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21 pages, 1207 KiB  
Review
Understanding Antibody Responses in Early Life: Baby Steps towards Developing an Effective Influenza Vaccine
by Elene A. Clemens and Martha A. Alexander-Miller
Viruses 2021, 13(7), 1392; https://0-doi-org.brum.beds.ac.uk/10.3390/v13071392 - 17 Jul 2021
Cited by 3 | Viewed by 3124
Abstract
The immune system of young infants is both quantitatively and qualitatively distinct from that of adults, with diminished responsiveness leaving these individuals vulnerable to infection. Because of this, young infants suffer increased morbidity and mortality from respiratory pathogens such as influenza viruses. The [...] Read more.
The immune system of young infants is both quantitatively and qualitatively distinct from that of adults, with diminished responsiveness leaving these individuals vulnerable to infection. Because of this, young infants suffer increased morbidity and mortality from respiratory pathogens such as influenza viruses. The impaired generation of robust and persistent antibody responses in these individuals makes overcoming this increased vulnerability through vaccination challenging. Because of this, an effective vaccine against influenza viruses in infants under 6 months is not available. Furthermore, vaccination against influenza viruses is challenging even in adults due to the high antigenic variability across viral strains, allowing immune evasion even after induction of robust immune responses. This has led to substantial interest in understanding how specific antibody responses are formed to variable and conserved components of influenza viruses, as immune responses tend to strongly favor recognition of variable epitopes. Elicitation of broadly protective antibody in young infants, therefore, requires that both the unique characteristics of young infant immunity as well as the antibody immunodominance present among epitopes be effectively addressed. Here, we review our current understanding of the antibody response in newborns and young infants and discuss recent developments in vaccination strategies that can modulate both magnitude and epitope specificity of IAV-specific antibody. Full article
(This article belongs to the Special Issue Antibodies and B Cell Memory in Viral Immunity)
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23 pages, 577 KiB  
Review
Requirement of Fc-Fc Gamma Receptor Interaction for Antibody-Based Protection against Emerging Virus Infections
by Shamus P. Keeler and Julie M. Fox
Viruses 2021, 13(6), 1037; https://0-doi-org.brum.beds.ac.uk/10.3390/v13061037 - 31 May 2021
Cited by 18 | Viewed by 4334
Abstract
Identification of therapeutics against emerging and re-emerging viruses remains a continued priority that is only reinforced by the recent SARS-CoV-2 pandemic. Advances in monoclonal antibody (mAb) isolation, characterization, and production make it a viable option for rapid treatment development. While mAbs are traditionally [...] Read more.
Identification of therapeutics against emerging and re-emerging viruses remains a continued priority that is only reinforced by the recent SARS-CoV-2 pandemic. Advances in monoclonal antibody (mAb) isolation, characterization, and production make it a viable option for rapid treatment development. While mAbs are traditionally screened and selected based on potency of neutralization in vitro, it is clear that additional factors contribute to the in vivo efficacy of a mAb beyond viral neutralization. These factors include interactions with Fc receptors (FcRs) and complement that can enhance neutralization, clearance of infected cells, opsonization of virions, and modulation of the innate and adaptive immune response. In this review, we discuss recent studies, primarily using mouse models, that identified a role for Fc-FcγR interactions for optimal antibody-based protection against emerging and re-emerging virus infections. Full article
(This article belongs to the Special Issue Antibodies and B Cell Memory in Viral Immunity)
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11 pages, 271 KiB  
Review
B-Cell Memory Responses to Variant Viral Antigens
by Harry N White
Viruses 2021, 13(4), 565; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040565 - 26 Mar 2021
Cited by 8 | Viewed by 3546
Abstract
A central feature of vertebrate immune systems is the ability to form antigen-specific immune memory in response to microbial challenge and so provide protection against future infection. In conflict with this process is the ability that many viruses have to mutate their antigens [...] Read more.
A central feature of vertebrate immune systems is the ability to form antigen-specific immune memory in response to microbial challenge and so provide protection against future infection. In conflict with this process is the ability that many viruses have to mutate their antigens to escape infection- or vaccine-induced antibody memory responses. Mutable viruses such as dengue virus, influenza virus and of course coronavirus have a major global health impact, exacerbated by this ability to evade immune responses through mutation. There have been several outstanding recent studies on B-cell memory that also shed light on the potential and limitations of antibody memory to protect against viral antigen variation, and so promise to inform new strategies for vaccine design. For the purposes of this review, the current understanding of the different memory B-cell (MBC) populations, and their potential to recognize mutant antigens, will be described prior to some examples from antibody responses against the highly mutable RNA based flaviviruses, influenza virus and SARS-CoV-2. Full article
(This article belongs to the Special Issue Antibodies and B Cell Memory in Viral Immunity)
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24 pages, 15350 KiB  
Review
Structural Analysis of Neutralizing Epitopes of the SARS-CoV-2 Spike to Guide Therapy and Vaccine Design Strategies
by Maxwell T. Finkelstein, Adam G. Mermelstein, Emma Parker Miller, Paul C. Seth, Erik-Stephane D. Stancofski and Daniela Fera
Viruses 2021, 13(1), 134; https://0-doi-org.brum.beds.ac.uk/10.3390/v13010134 - 19 Jan 2021
Cited by 45 | Viewed by 9549
Abstract
Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (nCoV or SARS-CoV-2). In this review, we highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) [...] Read more.
Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (nCoV or SARS-CoV-2). In this review, we highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2. Structural studies with SARS-CoV-2 neutralizing mAbs have revealed a diverse set of binding modes on the spike’s receptor-binding domain and N-terminal domain and highlight alternative targets on the spike. We consider this structural work together with mAb effects in vivo to suggest correlations between structure and clinical applications. We also place mAbs against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses in the context of the SARS-CoV-2 spike to suggest features that may be desirable to design mAbs or vaccines capable of conferring broad protection. Full article
(This article belongs to the Special Issue Antibodies and B Cell Memory in Viral Immunity)
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