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Vaccine Jun 2020We investigated humoral immune response to influenza A(H1N1)pdm infection and found 32 (22%) of the infected individuals identified by PCR failed to produce...
We investigated humoral immune response to influenza A(H1N1)pdm infection and found 32 (22%) of the infected individuals identified by PCR failed to produce a ≥ 4-fold hemagglutinin inhibition assay (HAI) response; a subset of 18 (56%) produced an alternate antibody response (against full-length HA, HA stalk, or neuraminidase). These individuals had lower pre-existing HAI antibody titers and showed a pattern of milder illness. An additional subset of 14 (44%) did not produce an alternate antibody response, had higher pre-existing antibody titers against full-length & stalk HA, and were less sick. These findings demonstrate that some individuals mount an alternate antibody response to influenza infection. In order to design more broadly protective influenza vaccines it may be useful to target these alternate sites. These findings support that there are influenza cases currently being missed by solely implementing HAI assays, resulting in an underestimation of the global burden of influenza infection.
Topics: Antibodies, Viral; Antibody Formation; Hemagglutination Inhibition Tests; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Influenza, Human
PubMed: 32389495
DOI: 10.1016/j.vaccine.2020.04.069 -
Nature Immunology Dec 2022Systems vaccinology has defined molecular signatures and mechanisms of immunity to vaccination. However, comparative analysis of immunity to different vaccines is...
Systems vaccinology has defined molecular signatures and mechanisms of immunity to vaccination. However, comparative analysis of immunity to different vaccines is lacking. We integrated transcriptional data of over 3,000 samples, from 820 adults across 28 studies of 13 vaccines and analyzed vaccination-induced signatures of antibody responses. Most vaccines induced signatures of innate immunity and plasmablasts at days 1 and 7, respectively, after vaccination. However, the yellow fever vaccine induced an early transient signature of T and B cell activation at day 1, followed by delayed antiviral/interferon and plasmablast signatures that peaked at days 7 and 14-21, respectively. Thus, there was no evidence for a 'universal signature' that predicted antibody response to all vaccines. However, accounting for the asynchronous nature of responses, we defined a time-adjusted signature that predicted antibody responses across vaccines. These results provide a transcriptional atlas of immunity to vaccination and define a common, time-adjusted signature of antibody responses.
Topics: Adult; Humans; Antibody Formation; Gene Expression Profiling; Vaccines; Vaccination; Immunity, Innate; Antibodies, Viral
PubMed: 36316475
DOI: 10.1038/s41590-022-01328-6 -
Frontiers in Immunology 2021Antibody-secreting cells (ASC), plasmablasts and plasma cells, are terminally differentiated B cells responsible for large-scale production and secretion of antibodies.... (Review)
Review
Antibody-secreting cells (ASC), plasmablasts and plasma cells, are terminally differentiated B cells responsible for large-scale production and secretion of antibodies. ASC are derived from activated B cells, which may differentiate extrafollicularly or form germinal center (GC) reactions within secondary lymphoid organs. ASC therefore consist of short-lived, poorly matured plasmablasts that generally secrete lower-affinity antibodies, or long-lived, highly matured plasma cells that generally secrete higher-affinity antibodies. The ASC population is responsible for producing an immediate humoral B cell response, the polyclonal antibody repertoire, as well as in parallel building effective humoral memory and immunity, or potentially driving pathology in the case of autoimmunity. ASC are phenotypically and transcriptionally distinct from other B cells and further distinguishable by morphology, varied lifespans, and anatomical localization. Single cell analyses are required to interrogate the functional and transcriptional diversity of ASC and their secreted antibody repertoire and understand the contribution of individual ASC responses to the polyclonal humoral response. Here we summarize the current and emerging functional and molecular techniques for high-throughput characterization of ASC with single cell resolution, including flow and mass cytometry, spot-based and microfluidic-based assays, focusing on functional approaches of the secreted antibodies: specificity, affinity, and secretion rate.
Topics: Animals; Antibody Formation; Antibody-Producing Cells; B-Lymphocytes; Gene Expression Profiling; Germinal Center; High-Throughput Screening Assays; Humans; Immunoassay; Plasma Cells; Single-Cell Analysis
PubMed: 35173713
DOI: 10.3389/fimmu.2021.821729 -
Cellular & Molecular Immunology Jun 2020In contrast to the previous belief that autoreactive B cells are eliminated from the normal repertoire of B cells, many autoreactive B cells actually escape clonal... (Review)
Review
In contrast to the previous belief that autoreactive B cells are eliminated from the normal repertoire of B cells, many autoreactive B cells actually escape clonal deletion and develop into mature B cells. These autoreactive B cells in healthy individuals perform some beneficial functions in the host and are homeostatically regulated by regulatory T and B cells or other mechanisms to prevent autoimmune diseases. Autoreactive B-1 cells constitutively produce polyreactive natural antibodies for tissue homeostasis. Recently, autoreactive follicular B cells were reported to participate actively in the germinal center reaction. Furthermore, the selection and usefulness of autoreactive marginal zone (MZ) B cells found in autoimmune diseases are not well understood, although the repertoire of MZ B-cell receptors (BCRs) is presumed to be biased to detect bacterial antigens. In this review, we discuss the autoreactive B-cell populations among all three major B-cell subsets and their regulation in immune responses and diseases.
Topics: Animals; Antibody Formation; B-Lymphocytes; Disease; Health; Homeostasis; Humans; Immunity
PubMed: 32382130
DOI: 10.1038/s41423-020-0445-4 -
Microbiology Spectrum Oct 2022Emerging infectious diseases represent a serious and ongoing threat to humans. Most emerging viruses are maintained in stable relationships with other species of...
Emerging infectious diseases represent a serious and ongoing threat to humans. Most emerging viruses are maintained in stable relationships with other species of animals, and their emergence within the human population results from cross-species transmission. Therefore, if we want to be prepared for the next emerging virus, we need to broadly characterize the diversity and ecology of viruses currently infecting other animals (i.e., the animal virosphere). High-throughput metagenomic sequencing has accelerated the pace of virus discovery. However, molecular assays can detect only active infections and only if virus is present within the sampled fluid or tissue at the time of collection. In contrast, serological assays measure long-lived antibody responses to infections, which can be detected within the blood, regardless of the infected tissues. Therefore, serological assays can provide a complementary approach for understanding the circulation of viruses, and while serological assays have historically been limited in scope, recent advancements allow thousands to hundreds of thousands of antigens to be assessed simultaneously using <1 μL of blood (i.e., highly multiplexed serology). The application of highly multiplexed serology for the characterization of the animal virosphere is dependent on the availability of reagents that can be used to capture or label antibodies of interest. Here, we evaluate the utility of commercial immunoglobulin-binding proteins (protein A and protein G) to enable highly multiplexed serology in 25 species of nonhuman mammals, and we describe a competitive fluorescence-linked immunosorbent assay (FLISA) that can be used as an initial screen for choosing the most appropriate capture protein for a given host species. Antibodies are generated in response to infections with viruses and other pathogens, and they help protect against future exposures. Mature antibodies are long lived, are highly specific, and can bind to their protein targets with high affinity. Thus, antibodies can also provide information about an individual's history of viral exposures, which has important applications for understanding the epidemiology and etiology of disease. In recent years, there have been large advances in the available methods for broadly characterizing antibody-binding profiles, but thus far, these have been utilized primarily with human samples only. Here, we demonstrate that commercial antibody-binding reagents can facilitate modern antibody assays for a wide variety of mammalian species, and we describe an inexpensive and fast approach for choosing the best reagent for each animal species. By studying antibody-binding profiles in captive and wild animals, we can better understand the distribution and prevalence of viruses that could spill over into humans.
Topics: Animals; Antibodies, Viral; Antibody Formation; Enzyme-Linked Immunosorbent Assay; Immunosorbents; Mammals
PubMed: 36125316
DOI: 10.1128/spectrum.02873-22 -
Frontiers in Immunology 2021Protection against pathogen re-infection is mediated, in large part, by two humoral cellular compartments, namely, long-lived plasma cells and memory B cells. Recent... (Review)
Review
Protection against pathogen re-infection is mediated, in large part, by two humoral cellular compartments, namely, long-lived plasma cells and memory B cells. Recent data have reinforced the importance of memory B cells, particularly in response to re-infection of different viral subtypes or in response with viral escape mutants. In regard to memory B cell generation, considerable advancements have been made in recent years in elucidating its basic mechanism, which seems to well explain why the memory B cells pool can deal with variant viruses. Despite such progress, efforts to develop vaccines that induce broadly protective memory B cells to fight against rapidly mutating pathogens such as influenza virus and HIV have not yet been successful. Here, we discuss recent advances regarding the key signals and factors regulating germinal center-derived memory B cell development and activation and highlight the challenges for successful vaccine development.
Topics: Antibodies, Neutralizing; Antibody Formation; Cell Communication; Cell Differentiation; Clonal Selection, Antigen-Mediated; Female; Germinal Center; Host-Pathogen Interactions; Humans; Immunologic Memory; Lymphocyte Activation; Lymphoid Progenitor Cells; Male; Memory B Cells; Receptors, Antigen, B-Cell; T-Lymphocyte Subsets
PubMed: 35095929
DOI: 10.3389/fimmu.2021.825813 -
Infection Feb 2022The coronavirus disease 2019 (COVID-19), caused by the novel betacoronavirus severe acute respiratory syndrome 2 (SARS-CoV-2), was declared a pandemic in March 2020. Due... (Review)
Review
OBJECTIVES
The coronavirus disease 2019 (COVID-19), caused by the novel betacoronavirus severe acute respiratory syndrome 2 (SARS-CoV-2), was declared a pandemic in March 2020. Due to the continuing surge in incidence and mortality globally, determining whether protective, long-term immunity develops after initial infection or vaccination has become critical.
METHODS/RESULTS
In this narrative review, we evaluate the latest understanding of antibody-mediated immunity to SARS-CoV-2 and to other coronaviruses (SARS-CoV, Middle East respiratory syndrome coronavirus and the four endemic human coronaviruses) in order to predict the consequences of antibody waning on long-term immunity against SARS-CoV-2. We summarise their antibody dynamics, including the potential effects of cross-reactivity and antibody waning on vaccination and other public health strategies. At present, based on our comparison with other coronaviruses we estimate that natural antibody-mediated protection for SARS-CoV-2 is likely to last for 1-2 years and therefore, if vaccine-induced antibodies follow a similar course, booster doses may be required. However, other factors such as memory B- and T-cells and new viral strains will also affect the duration of both natural and vaccine-mediated immunity.
CONCLUSION
Overall, antibody titres required for protection are yet to be established and inaccuracies of serological methods may be affecting this. We expect that with standardisation of serological testing and studies with longer follow-up, the implications of antibody waning will become clearer.
Topics: Antibody Formation; COVID-19; Humans; Middle East Respiratory Syndrome Coronavirus; Pandemics; SARS-CoV-2
PubMed: 34324165
DOI: 10.1007/s15010-021-01664-z -
Cell Jan 2023After vaccination or infection, long-lived germinal centers can produce antibodies with high affinity and specificity against pathogens. In this issue of Cell, de...
After vaccination or infection, long-lived germinal centers can produce antibodies with high affinity and specificity against pathogens. In this issue of Cell, de Carvalho et al. and Hägglöf et al. show that naive B cells can invade germinal centers, replacing B cells that entered early and changing features of antibody production. These findings have implications for vaccine design.
Topics: Germinal Center; B-Lymphocytes; Antibody Formation; Vaccination
PubMed: 36608649
DOI: 10.1016/j.cell.2022.12.023 -
Frontiers in Immunology 2022Multiple sclerosis (MS), a debilitating autoimmune inflammatory disease that affects the brain and spinal cord, causes demyelination of neurons, axonal damage, and... (Review)
Review
Multiple sclerosis (MS), a debilitating autoimmune inflammatory disease that affects the brain and spinal cord, causes demyelination of neurons, axonal damage, and neurodegeneration. MS and the murine experimental autoimmune encephalomyelitis (EAE) model have been viewed mainly as T-cell-mediated diseases. Emerging data have suggested the contribution of B-cells and autoantibodies to the disease progression. However, the underlying mechanisms by which dysregulated B-cells and antibody response promote MS and EAE remain largely unclear. Here, we provide an updated review of this specific subject by including B-cell biology and the role of B-cells in triggering autoimmune neuroinflammation with a focus on the regulation of antibody-producing B-cells. We will then discuss the role of a specific type of antibody, IgE, as it relates to the potential regulation of microglia and macrophage activation, autoimmunity and MS/EAE development. This knowledge can be utilized to develop new and effective therapeutic approaches to MS, which fits the scope of the Research Topic "Immune Mechanism in White Matter Lesions: Clinical and Pathophysiological Implications".
Topics: Animals; Antibody Formation; B-Lymphocytes; Encephalomyelitis, Autoimmune, Experimental; Immunoglobulin E; Mice; Multiple Sclerosis
PubMed: 35784370
DOI: 10.3389/fimmu.2022.900117 -
Frontiers in Immunology 2022Epithelial barriers, which include the gastrointestinal, respiratory, and genitourinary mucosa, compose the body's front line of defense. Since barrier tissues are... (Review)
Review
Epithelial barriers, which include the gastrointestinal, respiratory, and genitourinary mucosa, compose the body's front line of defense. Since barrier tissues are persistently exposed to microbial challenges, a rapid response that can deal with diverse invading pathogens is crucial. Because B cells have been perceived as indirectly contributing to immune responses through antibody production, B cells functioning in the peripheral organs have been outside the scope of researchers. However, recent evidence supports the existence of tissue-resident memory B cells (BRMs) in the lungs. This population's defensive response was stronger and faster than that of their circulating counterparts and could resist heterogeneous strains. With such traits, BRMs could be a promising target for vaccine design, but much about them remains to be revealed, including their locations, origin, specific markers, and the mechanisms of their establishment and maintenance. There is evidence for resident B cells in organs other than the lungs, suggesting that B cells are directly involved in the immune reactions of multiple non-lymphoid organs. This review summarizes the history of the discovery of BRMs and discusses important unresolved questions. Unique characteristics of humoral immunity that play an important role in the peripheral organs will be described briefly. Future research on B cells residing in non-lymphoid organs will provide new insights to help solve major problems regarding human health.
Topics: Antibody Formation; B-Lymphocytes; Humans; Immunity, Humoral; Memory B Cells; Mucous Membrane
PubMed: 35924234
DOI: 10.3389/fimmu.2022.953088