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Human Vaccines & Immunotherapeutics Oct 2021Neutralizing antibodies are the basis of almost all approved prophylactic vaccines and the foundation of effective protection from pathogens, including the recently...
Neutralizing antibodies are the basis of almost all approved prophylactic vaccines and the foundation of effective protection from pathogens, including the recently emerging SARS Coronavirus 2 (SARS-CoV-2). However, the contribution of antibodies to protection and to the course of the disease during first-time exposure to a pathogen is unknown. We analyzed the antibodies and B cell responses in severe and mild COVID-19 patients. Despite our primary assumption that high antibody titers contribute to a mild disease, we found that severe COVID-19 illness, and not mild infection, correlates with strong anti-viral antibody and memory B cell responses. This phenomenon was also demonstrated for anti-Mycobacterium inhibiting antibodies that we recently isolated from an actively infected Tuberculosis-sick donor. This correlation between disease severity and antibody responses can be explained by the fact that high viral loads drive B cell stimulation and generation of high-affinity antibodies that will be protective upon future encounter with the particular pathogen.
Topics: Antibodies, Neutralizing; Antibodies, Viral; Antibody Formation; COVID-19; Humans; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 34032550
DOI: 10.1080/21645515.2021.1929034 -
Trends in Immunology Mar 2021'Reverse vaccinology 2.0' aims to rationally reproduce template antibody responses, such as broadly neutralizing antibodies against human immunodeficiency virus-1. While... (Review)
Review
'Reverse vaccinology 2.0' aims to rationally reproduce template antibody responses, such as broadly neutralizing antibodies against human immunodeficiency virus-1. While observations of antibody convergence across individuals support the assumption that responses may be replicated, the diversity of humoral immunity and the process of antibody selection are rooted in stochasticity. Drawing from experience with in vitro antibody engineering by directed evolution, we consider how antibody selection may be driven, as in germline-targeting vaccine approaches to elicit broadly neutralizing antibodies and illustrate the potential consequences of over-defining a template antibody response. We posit that the prospective definition of template antibody responses and the odds of replicating them must be considered within the randomness of humoral immunity.
Topics: Antibodies, Neutralizing; Antibody Formation; HIV Antibodies; HIV-1; Humans; Prospective Studies
PubMed: 33514459
DOI: 10.1016/j.it.2021.01.001 -
Seminars in Immunopathology Mar 2019Vaccines are among the most impactful public health interventions, preventing millions of new infections and deaths annually worldwide. However, emerging data suggest... (Review)
Review
Vaccines are among the most impactful public health interventions, preventing millions of new infections and deaths annually worldwide. However, emerging data suggest that vaccines may not protect all populations equally. Specifically, studies analyzing variation in vaccine-induced immunity have pointed to the critical impact of genetics, the environment, nutrition, the microbiome, and sex in influencing vaccine responsiveness. The significant contribution of sex to modulating vaccine-induced immunity has gained attention over the last years. Specifically, females typically develop higher antibody responses and experience more adverse events following vaccination than males. This enhanced immune reactogenicity among females is thought to render females more resistant to infectious diseases, but conversely also contribute to higher incidence of autoimmunity among women. Dissection of mechanisms which underlie sex differences in vaccine-induced immunity has implicated hormonal, genetic, and microbiota differences across males and females. This review will highlight the importance of sex-dependent differences in vaccine-induced immunity and specifically will address the role of sex as a modulator of humoral immunity, key to long-term pathogen-specific protection.
Topics: Antibody Formation; Autoimmune Diseases; Female; Humans; Immunity, Humoral; Incidence; Infection Control; Infections; Male; Microbiota; Sex Characteristics; Vaccination; Vaccines
PubMed: 30547182
DOI: 10.1007/s00281-018-0726-5 -
Cell Reports Dec 2022Anelloviruses represent a major constituent of the commensal human virome; however, little is known about their immunobiology. Here, we present "AnelloScan," a T7 phage...
Anelloviruses represent a major constituent of the commensal human virome; however, little is known about their immunobiology. Here, we present "AnelloScan," a T7 phage library representing the open reading frame 1 (ORF1), ORF2, ORF3, and torque teno virus (TTV)-derived apoptosis-inducing protein (TAIP) sequences of more than 800 human anelloviruses and profile the antibody reactivities of serum samples from a cross-sectional cohort of 156 subjects by using phage-immunoprecipitation sequencing (PhIP-Seq). A majority of anellovirus peptides are not reactive in any of the subjects tested (n = ∼28,000; ∼85% of the library). Antibody-reactive peptides are largely restricted to the C-terminal region of the capsid protein ORF1. Moreover, using a longitudinal cohort of matched blood-transfusion donors and recipients, we find that most transmitted anelloviruses do not elicit a detectable antibody reactivity in the recipient and that the remainder elicit delayed responses appearing ∼100-150 days after transfusion.
Topics: Humans; Antibody Formation; Cross-Sectional Studies; Torque teno virus; Anelloviridae; Capsid Proteins
PubMed: 36543141
DOI: 10.1016/j.celrep.2022.111754 -
Nature Communications Dec 2023Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt...
Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission of respiratory pathogens. Live attenuated influenza vaccine (LAIV) is effective in preventing influenza in children, but a correlate of protection for LAIV remains unclear. Studying young adult volunteers, we observe that LAIV induces distinct, compartmentalized, antibody responses in the mucosa and blood. Seeking immunologic correlates of these distinct antibody responses we find associations with mucosal IL-33 release in the first 8 hours post-inoculation and divergent CD8 and circulating T follicular helper (cTfh) T cell responses 7 days post-inoculation. Mucosal antibodies are induced separately from blood antibodies, are associated with distinct immune responses early post-inoculation, and may provide a correlate of protection for mucosal vaccination. This study was registered as NCT04110366 and reports primary (mucosal antibody) and secondary (blood antibody, and nasal viral load and cytokine) endpoint data.
Topics: Child; Young Adult; Humans; Influenza Vaccines; Antibody Formation; Antibodies, Viral; Influenza, Human; Mucous Membrane; Vaccines, Attenuated; Immunity, Mucosal
PubMed: 38052824
DOI: 10.1038/s41467-023-43842-7 -
Autoimmunity Feb 2017Germinal centers (GCs) are dynamic microenvironments that form in the secondary lymphoid organs and generate somatically mutated high-affinity antibodies necessary to... (Review)
Review
Germinal centers (GCs) are dynamic microenvironments that form in the secondary lymphoid organs and generate somatically mutated high-affinity antibodies necessary to establish an effective humoral immune response. Tight regulation of GC responses is critical for maintaining self-tolerance. GCs can arise in the absence of purposeful immunization or overt infection (called spontaneous GCs, Spt-GCs). In autoimmune-prone mice and patients with autoimmune disease, aberrant regulation of Spt-GCs is thought to promote the development of somatically mutated pathogenic autoantibodies and the subsequent development of autoimmunity. The mechanisms that control the formation of Spt-GCs and promote systemic autoimmune diseases remain an open question and the focus of ongoing studies. Here, we discuss the most current studies on the role of Spt-GCs in autoimmunity.
Topics: Animals; Antibody Formation; Autoantibodies; Autoimmune Diseases; Autoimmunity; B-Lymphocytes; Biomarkers; Gene Expression Regulation; Germinal Center; Humans; Immune Tolerance; Protein Binding; Signal Transduction; Somatic Hypermutation, Immunoglobulin
PubMed: 28166685
DOI: 10.1080/08916934.2017.1280671 -
American Journal of Respiratory Cell... Feb 2023
Topics: Eosinophils; Antibody Formation; Lung; Cytokines
PubMed: 36306503
DOI: 10.1165/rcmb.2022-0410ED -
MAbs 2020The origins of the various elements in the human antibody repertoire have been and still are subject to considerable uncertainty. Uncertainty in respect of whether the... (Review)
Review
The origins of the various elements in the human antibody repertoire have been and still are subject to considerable uncertainty. Uncertainty in respect of whether the various elements have always served a specific defense function or whether they were co-opted from other organismal roles to form a crude naïve repertoire that then became more complex as combinatorial mechanisms were added. Estimates of the current size of the human antibody naïve repertoire are also widely debated with numbers anywhere from 10 million members, based on experimentally derived numbers, to in excess of one thousand trillion members or more, based on the different sequences derived from theoretical combinatorial calculations. There are questions that are relevant at both ends of this number spectrum. At the lower bound it could be questioned whether this is an insufficient repertoire size to counter all the potential antigen-bearing pathogens. At the upper bound the question is rather simpler: How can any individual interrogate such an astronomical number of antibody-bearing B cells in a timeframe that is meaningful? This review evaluates the evolutionary aspects of the adaptive immune system, the calculations that lead to the large repertoire estimates, some of the experimental evidence pointing to a more restricted repertoire whose variation appears to derive from convergent 'structure and specificity features', and includes a theoretical model that seems to support it. Finally, a solution that may reconcile the size difference anomaly, which is still a hot subject of debate, is suggested.
Topics: Antibody Formation; Humans
PubMed: 32097086
DOI: 10.1080/19420862.2020.1729683 -
EMBO Reports Apr 2020Efficient antibody production is a crucial step during immune responses leading to pathogen clearance and neutralization. Immune synapses, contact points between T and B...
Efficient antibody production is a crucial step during immune responses leading to pathogen clearance and neutralization. Immune synapses, contact points between T and B lymphocytes in the presence of an antigen, are necessary to initiate the proliferation and differentiation of B cells in the germinal center. In this issue of EMBO Reports, Fernández-Messina et al [1] present evidence of microRNA transfer from T to B cells via exosomes during synapse formation and highlight the crucial role of these exosomes for germinal center formation and the efficient production of antigen-specific antibodies.
Topics: Antibody Formation; B-Lymphocytes; Exosomes; Germinal Center; MicroRNAs
PubMed: 32147923
DOI: 10.15252/embr.202050190 -
Seminars in Immunopathology Oct 2021Antibodies are key elements of protective immunity. In the mucosal immune system in particular, secretory immunoglobulin A (SIgA), the most abundantly produced antibody... (Review)
Review
Antibodies are key elements of protective immunity. In the mucosal immune system in particular, secretory immunoglobulin A (SIgA), the most abundantly produced antibody isotype, protects against infections, shields the mucosal surface from toxins and environmental factors, and regulates immune homeostasis and a peaceful coexistence with our microbiota. However, the dark side of IgA biology promotes the formation of immune complexes and provokes pathologies, e.g., IgA nephropathy (IgAN). The precise mechanisms of how IgA responses become deregulated and pathogenic in IgAN remain unresolved. Yet, as the field of microbiota research moved into the limelight, our basic understanding of IgA biology has been taking a leap forward. Here, we discuss the structure of IgA, the anatomical and cellular foundation of mucosal antibody responses, and current concepts of how we envision the interaction of SIgA and the microbiota. We center on key concepts in the field while taking account of both historic findings and exciting new observations to provide a comprehensive groundwork for the understanding of IgA biology from the perspective of a mucosal immunologist.
Topics: Antibody Formation; Glomerulonephritis, IGA; Humans; Immunity, Mucosal; Immunoglobulin A, Secretory; Microbiota
PubMed: 34379174
DOI: 10.1007/s00281-021-00879-4