Shared and unique antibody and B cell profiles in HIV-positive and HIV-negative individuals with cryptococcal meningoencephalitis.

Host non-T cell markers to aid in the diagnosis of cryptococcal meningoencephalitis (CM) have not been identified. In this case-control study, we characterized antibody and B cell profiles in HIV-negative and HIV-positive Vietnamese individuals of the Kinh ethnicity recently diagnosed with CM and controls. The study included 60 HIV-negative with no known immunocompromising condition and 60 HIV-positive individuals, with 30 CM cases and 30 controls in each group.

SARS-CoV-2 multi-antigen protein microarray for detailed characterization of antibody responses in COVID-19 patients.

Antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target multiple epitopes on different domains of the spike protein, and other SARS-CoV-2 proteins. We developed a SARS-CoV-2 multi-antigen protein microarray with the nucleocapsid, spike and its domains (S1, S2), and variants with single (D614G, E484K, N501Y) or double substitutions (N501Y/Deletion69/70), allowing a more detailed high-throughput analysis of the antibody repertoire following infection. The assay was demonstrated to be reliable and comparable to ELISA.

Association of Antibody Immunity With Cryptococcal Antigenemia and Mortality in a South African Cohort With Advanced Human Immunodeficiency Virus Disease.

Background: Asymptomatic cryptococcal antigenemia (positive blood cryptococcal antigen [CrAg]) is associated with increased mortality in individuals with human immunodeficiency virus (HIV) even after adjusting for CD4 count and despite receiving antifungal treatment. The association of antibody immunity with mortality in adults with HIV with cryptococcal antigenemia is unknown.

Methods: Cryptococcal capsular glucuronoxylomannan (GXM)- and naturally occurring β-glucans (laminarin, curdlan)-binding antibodies were measured in blood samples of 197 South Africans with HIV who underwent CrAg screening and were followed up to 6 months.

Specific and Non--Specific Antibody Profiles in Organ Transplant Recipients With and Without Cryptococcosis.

Antibody immunity has not been studied in organ transplant recipients (OTRs) with cryptococcosis. We determined serum antibody levels in OTRs: 23 cryptococcosis cases and 21 controls. Glucuronoxylomannan immunoglobulin M (IgM) and laminarin IgM were lower in cases than controls, were inversely associated with cryptococcosis status, and may hold promise as markers of cryptococcosis.

Single-Dilution COVID-19 Antibody Test with Qualitative and Quantitative Readouts.

The coronavirus disease 2019 (COVID-19) global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to place an immense burden on societies and health care systems. A key component of COVID-19 control efforts is serological testing to determine the community prevalence of SARS-CoV-2 exposure and quantify individual immune responses to prior SARS-CoV-2 infection or vaccination. Here, we describe a laboratory-developed antibody test that uses readily available research-grade reagents to detect SARS-CoV-2 exposure in patient blood samples with high sensitivity and specificity.

Treatment of severe COVID-19 with convalescent plasma in Bronx, NYC.

Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as a treatment for coronavirus disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200 mL of CCP with a spike protein IgG titer ≥ 1:2430 (median 1:47,385) within 72 hours of admission with propensity score-matched controls cared for at a medical center in the Bronx, between April 13 and May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroid use, and anticoagulation use.

Treatment of Severe COVID-19 with Convalescent Plasma in the Bronx, NYC.

Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as treatment for Coronavirus Disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200mL of CCP with a Spike protein IgG titer ≥1:2,430 (median 1:47,385) within 72 hours of admission to propensity score-matched controls cared for at a medical center in the Bronx, between April 13 to May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroids, and anticoagulation use.

Antibody Responses in HIV-Infected Patients With Advanced Immunosuppression and Asymptomatic Cryptococcal Antigenemia.

Background: There are no host biomarkers of risk for HIV-associated cryptococcal meningitis (CM) except CD4+ T-cell deficiency. At present, serum cryptococcal antigen (CrAg) screening of those with CD4 <100 cells/µL is used to identify persons at risk for HIV-associated CM. We determined if plasma antibody profiles could discriminate CrAg+ from CrAg- patients.

Association Between Plasma Antibody Responses and Risk for Cryptococcus-Associated Immune Reconstitution Inflammatory Syndrome.

Background: Initiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected individuals with cryptococcal meningitis places them at risk for Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS). The relationship between antibody immunity and C-IRIS risk has not been investigated.

Methods: We compared plasma levels of immunoglobulins, C.

Antibody and B Cell Subset Perturbations in Human Immunodeficiency Virus-Uninfected Patients With Cryptococcosis.

The importance of antibody immunity in protection against remains unresolved. We measured serum -specific and total antibody levels and peripheral blood B cell subsets of 12 previously healthy patients with cryptococcosis (cases) and 21 controls. Before and after adjustment for age, sex, and race, cryptococcal capsular polysaccharide immunoglobulin G was higher in cases than controls, whereas total B and memory B cell levels were lower.

A Small Protein Associated with Fungal Energy Metabolism Affects the Virulence of Cryptococcus neoformans in Mammals.

The pathogenic yeast Cryptococcus neoformans causes cryptococcosis, a life-threatening fungal disease. C. neoformans has multiple virulence mechanisms that are non-host specific, induce damage and interfere with immune clearance.

Structural Characterization of Melanin Pigments from Commercial Preparations of the Edible Mushroom Auricularia auricula.

Many of the most widely consumed edible mushrooms are pigmented, and these have been associated with some beneficial health effects. Nevertheless, the majority of the reported compounds associated with these desirable properties are non-pigmented. We have previously reported that melanin pigment from the edible mushroom Auricularia auricula can protect mice against ionizing radiation, although no physicochemical characterization was reported.

Variable Region Identical IgA and IgE to Cryptococcus neoformans Capsular Polysaccharide Manifest Specificity Differences.

In recent years several groups have shown that isotype switching from IgM to IgG to IgA can affect the affinity and specificity of antibodies sharing identical variable (V) regions. However, whether the same applies to IgE is unknown. In this study we compared the fine specificity of V region-identical IgE and IgA to Cryptococcus neoformans capsular polysaccharide and found that these differed in specificity from each other.

Combinations of monoclonal antibodies to anthrax toxin manifest new properties in neutralization assays.

Monoclonal antibodies (MAbs) are potential therapeutic agents against Bacillus anthracis toxins, since there is no current treatment to counteract the detrimental effects of toxemia. In hopes of isolating new protective MAbs to the toxin component lethal factor (LF), we used a strain of mice (C57BL/6) that had not been used in previous studies, generating MAbs to LF. Six LF-binding MAbs were obtained, representing 3 IgG isotypes and one IgM.

Antibody binding to Cryptococcus neoformans impairs budding by altering capsular mechanical properties.

Abs to microbial capsules are critical for host defense against encapsulated pathogens, but very little is known about the effects of Ab binding on the capsule, apart from producing qualitative capsular reactions ("quellung" effects). A problem in studying Ab-capsule interactions is the lack of experimental methodology, given that capsules are fragile, highly hydrated structures. In this study, we pioneered the use of optical tweezers microscopy to study Ab-capsule interactions.

Variable region identical immunoglobulins differing in isotype express different paratopes.

The finding that the antibody (Ab) constant (C) region can influence fine specificity suggests that isotype switching contributes to the generation of Ab diversity and idiotype restriction. Despite the centrality of this observation for diverse immunological effects such as vaccine responses, isotype-restricted antibody responses, and the origin of primary and secondary responses, the molecular mechanism(s) responsible for this phenomenon are not understood. In this study, we have taken a novel approach to the problem by probing the paratope with (15)N label peptide mimetics followed by NMR spectroscopy and fluorescence emission spectroscopy.

The constant region contributes to the antigenic specificity and renal pathogenicity of murine anti-DNA antibodies.

Affinity for DNA and cross-reactivity with renal antigens are associated with enhanced renal pathogenicity of lupus autoantibodies. In addition, certain IgG subclasses are enriched in nephritic kidneys, suggesting that isotype may determine the outcome of antibody binding to renal antigens. To investigate if the isotype of DNA antibodies affects renal pathogenicity by influencing antigen binding, we derived IgM, IgG1, IgG2b and IgG2a forms of the PL9-11 antibody (IgG3 anti-DNA) by in vitro class switching or PCR cloning.

Fungal melanins differ in planar stacking distances.

Melanins are notoriously difficult to study because they are amorphous, insoluble and often associated with other biological materials. Consequently, there is a dearth of structural techniques to study this enigmatic pigment. Current models of melanin structure envision the stacking of planar structures.

Bacillus anthracis produces membrane-derived vesicles containing biologically active toxins.

Extracellular vesicle production is a ubiquitous process in Gram-negative bacteria, but little is known about such process in Gram-positive bacteria. We report the isolation of extracellular vesicles from the supernatants of Bacillus anthracis, a Gram-positive bacillus that is a powerful agent for biological warfare. B.

Radiolabeled antibodies to Bacillus anthracis toxins are bactericidal and partially therapeutic in experimental murine anthrax.

Bacillus anthracis is a powerful agent for use in biological warfare, and infection with the organism is associated with a high rate of mortality, underscoring the need for additional effective therapies for anthrax. Radioimmunotherapy (RIT) takes advantage of the specificity and affinity of the antigen-antibody interaction to deliver a microbicidal radioactive nuclide to a site of infection. RIT has proven therapeutic in experimental models of viral, bacterial, and fungal infections; but it is not known whether this approach can successfully employ toxin binding monoclonal antibodies (MAbs) for diseases caused by toxigenic bacteria.

Identification of linear epitopes in Bacillus anthracis protective antigen bound by neutralizing antibodies.

Protective antigen (PA), the binding subunit of anthrax toxin, is the major component in the current anthrax vaccine, but the fine antigenic structure of PA is not well defined. To identify linear neutralizing epitopes of PA, 145 overlapping peptides covering the entire sequence of the protein were synthesized. Six monoclonal antibodies (mAbs) and antisera from mice specific for PA were tested for their reactivity to the peptides by enzyme-linked immunosorbent assays.

The common Cryptococcus neoformans glucuronoxylomannan M2 motif elicits non-protective antibodies.

The Cryptococcus neoformans capsular glucuronoxylomannan (GXM) is a potential vaccine antigen that can elicit protective and non-protective antibodies. In an attempt to focus the immune response on a single antigenic component, a heptasaccharide oligosaccharide representing the major structural motif (M2) of the most common clinical isolate was synthesized and conjugated to human serum albumin (HSA). Monoclonal antibodies (mAbs) generated from mice immunized with M2-HSA produced the characteristic punctuate immunofluorescence associated with non-protective mAbs.