-
The Journal of Infectious Diseases Jun 2024Young children and older adults are susceptible for invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Pneumococcal protein-specific antibodies play...
BACKGROUND
Young children and older adults are susceptible for invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Pneumococcal protein-specific antibodies play a protective role against IPD; however, not much is known about the pace of acquisition, maturation, and maintenance of these antibodies throughout life.
METHODS
Immunoglobulin G (IgG) and IgA levels, avidity, and/or specificity to the pneumococcal proteome in serum and saliva from healthy young children, adults, and older adults, with known carriage status, were measured by enzyme-linked immunosorbent assay (ELISA) and 2-dimensional western blotting against ΔcpsTIGR4.
RESULTS
Eleven-month-old children, the youngest age group tested, had the lowest pneumococcal proteome-specific IgG and IgA levels and avidity in serum and saliva, followed by 24-month-old children and were further elevated in adult groups. Among adult groups, the parents had the highest serum and saliva IgG and IgA antibody levels. In children, antibody levels and avidity correlated with daycare attendance and presence of siblings, posing as proxy for exposure and immunization. Immunodominance patterns slightly varied throughout life.
CONCLUSIONS
Humoral immunity against the pneumococcal proteome is acquired through multiple episodes of pneumococcal exposure. Low-level and low-avidity antiproteome antibody profiles in young children may contribute to their IPD susceptibility, while in overall antiproteome antibody-proficient older adults other factors likely play a role.
PubMed: 38888894
DOI: 10.1093/infdis/jiae255 -
Journal of Medical Virology Jun 2024Human immunodeficiency virus (HIV) infection is still a global public health issue, and the development of an effective prophylactic vaccine inducing potent neutralizing...
Human immunodeficiency virus (HIV) infection is still a global public health issue, and the development of an effective prophylactic vaccine inducing potent neutralizing antibodies remains a significant challenge. This study aims to explore the inflammation-related proteins associated with the neutralizing antibodies induced by the DNA/rTV vaccine. In this study, we employed the Olink chip to analyze the inflammation-related proteins in plasma in healthy individuals receiving HIV candidate vaccine (DNA priming and recombinant vaccinia virus rTV boosting) and compared the differences between neutralizing antibody-positive (nab + ) and -negative(nab-) groups. We identified 25 differentially expressed factors and conducted enrichment and correlation analysis on them. Our results revealed that significant expression differences in artemin (ARTN) and C-C motif chemokine ligand 23 (CCL23) between nab+ and -nab- groups. Notably, the expression of CCL23 was negatively corelated to the ID of neutralizing antibodies and the intensity of the CD4 T cell responses. This study enriches our understanding of the immune picture induced by the DNA/rTV vaccine, and provides insights for future HIV vaccine development.
Topics: Humans; Antibodies, Neutralizing; Vaccinia virus; HIV Antibodies; HIV-1; Adult; Proteomics; AIDS Vaccines; Male; HIV Infections; Vaccines, DNA; Female; Healthy Volunteers; Vaccines, Synthetic; Plasma; Young Adult
PubMed: 38888113
DOI: 10.1002/jmv.29749 -
RMD Open Jun 2024The objective of this study is to evaluate whether anti-neutrophil cytoplasmic antibody (ANCA) seropositivity and antigen specificity at diagnosis have predictive...
OBJECTIVES
The objective of this study is to evaluate whether anti-neutrophil cytoplasmic antibody (ANCA) seropositivity and antigen specificity at diagnosis have predictive utility in paediatric-onset small vessel vasculitis.
METHODS
Children and adolescents with small vessel vasculitis (n=406) stratified according to the absence (n=41) or presence of ANCA for myeloperoxidase (MPO) (n=129) and proteinase-3 (PR3) (n=236) were compared for overall and kidney-specific disease activity at diagnosis and outcomes between 1 and 2 years using retrospective clinical data from the ARChiVe/Paediatric Vasculitis Initiative registry to fit generalised linear models.
RESULTS
Overall disease activity at diagnosis was higher in PR3-ANCA and MPO-ANCA-seropositive individuals compared with ANCA-negative vasculitis. By 1 year, there were no significant differences, based on ANCA positivity or specificity, in the likelihood of achieving inactive disease (~68%), experiencing improvement (≥87%) or acquiring damage (~58%). Similarly, and in contrast to adult-onset ANCA-associated vasculitis, there were no significant differences in the likelihood of having a relapse (~11%) between 1 and 2 years after diagnosis. Relative to PR3-ANCA, MPO-ANCA seropositivity was associated with a higher likelihood of kidney involvement (OR 2.4, 95% CI 1.3 to 4.7, p=0.008) and severe kidney dysfunction (Kidney Disease Improving Global Outcomes (KDIGO) stages 4-5; OR 6.04, 95% CI 2.77 to 13.57, p<0.001) at onset. Nonetheless, MPO-ANCA seropositive individuals were more likely to demonstrate improvement in kidney function (improved KDIGO category) within 1 year of diagnosis than PR3-ANCA seropositive individuals with similarly severe kidney disease at onset (p<0.001).
CONCLUSIONS
The results of this study suggest important paediatric-specific differences in the predictive value of ANCA compared with adult patients that should be considered when making treatment decisions in this population.
Topics: Humans; Antibodies, Antineutrophil Cytoplasmic; Male; Female; Child; Adolescent; Peroxidase; Myeloblastin; Retrospective Studies; Kidney Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Biomarkers; Child, Preschool; Prognosis; Predictive Value of Tests
PubMed: 38886004
DOI: 10.1136/rmdopen-2024-004315 -
JCI Insight Jun 2024Antibody-mediated depletion studies have demonstrated that CD8+ T cells are required for effective immune control of SIV. However, this approach is confounded by several...
Antibody-mediated depletion studies have demonstrated that CD8+ T cells are required for effective immune control of SIV. However, this approach is confounded by several factors, including reactive CD4+ T cell proliferation, and further provides no specificity information. We circumvented these limitations by selectively depleting CD8+ T cells specific for the Gag epitope CTPYDINQM (CM9) via the administration of immunotoxin-conjugated tetrameric complexes of CM9/Mamu-A*01. Immunotoxin administration effectively depleted circulating but not tissuelocalized CM9-specific CD8+ T cells, akin to the bulk depletion pattern observed with antibodies directed against CD8. However, we found no evidence to indicate that circulating CM9-specific CD8+ T cells suppressed viral replication in Mamu-A*01+ rhesus macaques during acute or chronic progressive infection with a pathogenic strain of SIV. This observation extended to macaques with established infection during and after continuous antiretroviral therapy. In contrast, natural controller macaques experienced dramatic increases in plasma viremia after immunotoxin administration, highlighting the importance of CD8+ T cell-mediated immunity against CM9. Collectively, these data showed that CM9-specific CD8+ T cells were necessary but not sufficient for robust immune control of SIV in a nonhuman primate model and, more generally, validated an approach that could inform the design of next-generation vaccines against HIV-1.
PubMed: 38885329
DOI: 10.1172/jci.insight.174168 -
Molecular Therapy. Methods & Clinical... Jun 2024Over 4% of the global population is estimated to live with autoimmune disease, necessitating immunosuppressive treatment that is often chronic, not curative, and carries...
Over 4% of the global population is estimated to live with autoimmune disease, necessitating immunosuppressive treatment that is often chronic, not curative, and carries associated risks. B cells have emerged as key players in disease pathogenesis, as evidenced by partial responsiveness to B cell depletion by antibody-based therapies. However, these treatments often have transient effects due to incomplete depletion of tissue-resident B cells. Chimeric antigen receptor (CAR) T cells targeting B cells have demonstrated efficacy in refractory systemic lupus erythematosus. To this end, we developed an anti-CD19 CAR T cell product candidate, CABA-201, containing a clinically evaluated fully human CD19 binder (IC78) with a 4-1BB costimulatory domain and CD3 zeta stimulation domain for treatment refractory autoimmune disease. Here, we demonstrate specific cytotoxic activity of CABA-201 against CD19 Nalm6 cells with no off-target effects on primary human cells. Novel examination of CABA-201 generated from primary T cells from multiple patients with autoimmune disease displayed robust CAR surface expression and effective elimination of the intended target autologous CD19 B cells . Together, these findings support the tolerability and activity of CABA-201 for clinical development in patients with autoimmune disease.
PubMed: 38883975
DOI: 10.1016/j.omtm.2024.101267 -
Journal of Pregnancy 2024There is insufficient evidence to assess the risk of the production of clinically important alloimmune irregular red blood cell (RBC) antibodies in first-time pregnant... (Comparative Study)
Comparative Study
Comparison of the Detection Rate and Specificity of Irregular Red Blood Cell Antibodies Between First-Time Pregnant Women and Women With a History of Multiple Pregnancies Among 18,010 Chinese Women.
There is insufficient evidence to assess the risk of the production of clinically important alloimmune irregular red blood cell (RBC) antibodies in first-time pregnant women. Using the microcolumn gel antiglobulin method, 18,010 Chinese women with a history of pregnancy and pregnant women were screened for irregular RBC antibodies, and for those with positive test results, antibody specificity was determined. The detection rate and specificity of irregular RBC antibodies in women with a history of multiple pregnancies (two or more) and first-time pregnant women were determined. In addition to 25 patients who passively acquired anti-D antibodies via an intravenous anti-D immunoglobulin injection, irregular RBC antibodies were detected in 121 (0.67%) of the 18,010 women. Irregular RBC antibodies were detected in 93 (0.71%) of the 13,027 women with a history of multiple pregnancies, and antibody specificity was distributed mainly in the Rh, MNSs, Lewis, and Kidd blood group systems; irregular RBC antibodies were detected in 28 (0.56%) of the 4983 first-time pregnant women, and the antibody specificity was distributed mainly in the MNSs, Rh, and Lewis blood group systems. The difference in the percentage of patients with irregular RBC antibodies between the two groups was insignificant ( = 1.248, > 0.05). Of the 121 women with irregular RBC antibodies, nine had anti-Mur antibodies, and one had anti-Di antibodies; these antibodies are clinically important but easily missed because the antigenic profile of the reagent RBCs that are commonly used in antibody screens does not include the antigens that are recognized by these antibodies. Irregular RBC antibody detection is clinically important for both pregnant women with a history of multiple pregnancies and first-time pregnant women. Mur and Di should be included in the antigenic profile of reagent RBCs that are used for performing antibody screens in the Chinese population.
Topics: Humans; Female; Pregnancy; Erythrocytes; China; Adult; Pregnancy, Multiple; Isoantibodies; Rho(D) Immune Globulin; Sensitivity and Specificity; Antibody Specificity; MNSs Blood-Group System; Asian People; Kidd Blood-Group System; East Asian People
PubMed: 38883212
DOI: 10.1155/2024/5539776 -
Microbes and Infection Jun 2024Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is one of the mechanisms contributing to increased severity during heterotypic, secondary...
Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is one of the mechanisms contributing to increased severity during heterotypic, secondary infection. The complement protein C1q has been shown to reduce the magnitude of ADE in vitro. Therefore, we investigated the mechanisms of C1q modulation of ADE, focusing on processes of viral entry. Using a model of ADE of DENV-1 infection in human myeloid cell lines in the presence of monoclonal antibodies, 4G2 and 2H2, we found that C1q produced nearly a 40-fold reduction of ADE of DENV-1 in K562 cells, but had no effect in U937 cells. In K562 cells, C1q reduced adsorption of DENV-1/4G2 and exerted a dual inhibitory effect on adsorption and internalization of DENV-1/2H2. Distinct endocytic pathways in the presence of antibody corresponded to conditions where C1q produced a differential action. Also, C1q did not affect the intrinsic cell response mediated by FcγR in human myeloid cells. The modulation of ADE of DENV-1 by C1q is dependent on the FcγR expressed on immune cells and the specificity of the antibody comprising the immune complex. Understanding protective and pathogenic mechanisms in the humoral response to DENV infections is crucial for the successful design of antivirals and vaccines.
PubMed: 38880233
DOI: 10.1016/j.micinf.2024.105378 -
Virology Jun 2024The hemagglutinin-esterase-fusion (HEF) protein binds 9-O-acetylated sialic acids-containing glycans on the cell surface and drives influenza D virus (IDV) entry. The...
The hemagglutinin-esterase-fusion (HEF) protein binds 9-O-acetylated sialic acids-containing glycans on the cell surface and drives influenza D virus (IDV) entry. The HEF is a primary determinant of the exceptional thermal and acid stability observed in IDV infection biology. Here, we expressed and purified the receptor binding domain (RBD) of the IDV HEF protein in Escherichia coli and characterized its receptor binding and antigenic properties. The data from these experiments indicate that (i) the RBD can bind with specificity to turkey red blood cells (RBC), and its binding can be specifically inhibited by IDV antibody; (ii) the RBD efficiently binds to the cell surface of MDCK cells expressing the receptor of IDV; and (iii) anti-RBD antibodies are capable of blocking RBD attachment to MDCK cells as well as of inhibiting the virus from agglutinating RBCs. These observations support the utility of this RBD in future receptor and entry studies of IDV.
PubMed: 38880069
DOI: 10.1016/j.virol.2024.110138 -
Journal of Chromatography. B,... Jun 2024Protein A (ProA) high-performance liquid chromatography (HPLC) is a common analytical procedure for measuring monoclonal antibody (mAb) titers due to its high...
Protein A (ProA) high-performance liquid chromatography (HPLC) is a common analytical procedure for measuring monoclonal antibody (mAb) titers due to its high specificity and efficiency. Accurate and reliable results of this procedure are imperative, as the quantitation of the total mAb present for in-process samples directly impacts downstream purification steps related to the removal of process-related impurities. This study aimed to improve a platform ProA HPLC analytical procedure which was previously developed using traditional approaches and was not always reliable. By retrospectively applying Analytical Quality by Design (AQbD) principles and statistical assessments of performance, a bias in the calibration standard due to protein-adsorption to common sample vial materials was identified. The inclusion of Tween® 20 into the mobile phase used as sample diluent was optimized to ensure procedure performance and improve analytical range. The resulting procedure robustness was evaluated using Design of Experiment (DoE) approaches and performance was verified against Analytical Target Profile (ATP) criteria as recommended by regulatory agencies. The resulting linearity displayed R values of 1.00 with intercept biases of 1.2 % (analyst 1) and 0.8 % (analyst 2), accuracy across all levels was reported at 99.2 % recovery, and intermediate precision was reported as 3.0 % RSD. Application of this new platform procedure has since reduced development timelines for new mAb products by 50 % and allowed for accurate titer determination to support >5 early phase product-specific process decisions without requiring extensive analytical procedure development. This work demonstrates the utility and relative ease of adopting AQbD concepts, even for established procedures, and supporting them with a lifecycle approach to managing procedure performance.
PubMed: 38880058
DOI: 10.1016/j.jchromb.2024.124205 -
Analytica Chimica Acta Aug 2024Mycotoxins are commonly found in food materials and severely threaten human health. Antibodies play a key role as a part of immunological techniques in detecting...
Mycotoxins are commonly found in food materials and severely threaten human health. Antibodies play a key role as a part of immunological techniques in detecting mycotoxins. Therefore, highly specific antibodies and detection techniques against mycotoxins need to be developed for advancements in medical research. In this study, we presented a novel strategy for quickly screening highly specific antigen-binding fragment (Fab) antibodies based on yeast surface display (YSD) and detecting small-molecule compounds based on a YSD biosensor. We constructed a yeast surface display Deoxynivalenol (DON)-Fab library with 10 cfu/mL with a galactose-inducible bidirectional promoter. By conducting efficient magnetic-activated cell sorting and fluorescence-activated cell sorting (MACS/FACS), four kinds of DON-selective yeasts were screened. As Fab@YSD C4# showed high sensitivity, we used it to build a one-pot Fab@YSD chemiluminescence biosensor with DON-BSA@Biotin and Streptavidin-alkaline phosphatase (SA-ALP). This method showed a low operational threshold (LOD = 0.166 pg/mL) and a high population range (linear range = 0.001-132.111 ng/mL) within 40 min, which facilitated the detection of DON with high specificity and better recovery in real samples (wheat, corn, flour, and cornmeal). Our results suggested that the Fab@YSD chemiluminescence biosensor is an inexpensive, reproducible, user-friendly, and sensitive method for detecting DON and may be used to quickly detect other small-molecule contaminants in food items.
Topics: Trichothecenes; Biosensing Techniques; Saccharomyces cerevisiae; Food Contamination; Immunoglobulin Fab Fragments; Limit of Detection; Triticum; Zea mays; Flour
PubMed: 38879206
DOI: 10.1016/j.aca.2024.342760