scholarly journals Characterization of the Opsonic and Protective Activity against Staphylococcus aureus of Fully Human Monoclonal Antibodies Specific for the Bacterial Surface Polysaccharide Poly-N-Acetylglucosamine

2006 ◽  
Vol 74 (5) ◽  
pp. 2742-2750 ◽  
Author(s):  
Casie Kelly-Quintos ◽  
Lisa A. Cavacini ◽  
Marshall R. Posner ◽  
Donald Goldmann ◽  
Gerald B. Pier
Keyword(s):  
Staphylococcus Aureus ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Protective Efficacy ◽  
Human Monoclonal Antibodies ◽  
Variable Regions ◽  
Bacterial Surface ◽  
Complement Deposition

ABSTRACT Carbohydrate antigens are important targets of the immune system in clearing bacterial pathogens. Although the immune system almost exclusively uses antibodies in response to foreign carbohydrates, there is still much to learn about the role of different epitopes on the carbohydrate as targets of protective immunity. We examined the role of acetyl group-dependent and -independent epitopes on the staphylococcal surface of polysaccharide poly-N-acetylated glucosamine (PNAG) by use of human monoclonal antibodies (MAbs) specific for such epitopes. We utilized hybridoma technology to produce fully human immunoglobulin G2 (IgG2) MAbs from B cells of an individual post-Staphylococcus aureus infection and cloned the antibody variable regions to produce an IgG1 form of each original MAb. Specificity and functionality of the purified MAbs were tested in vitro using enzyme-linked immunosorbent assays, complement deposition, and opsonophagocytic assays. We found that a MAb (MAb F598) that bound the best to nonacetylated or backbone epitopes on PNAG had superior complement deposition and opsonophagocytic activity compared to two MAbs that bound optimally to PNAG that was expressed with a native level (>90%) of N-acetyl groups (MAbs F628 and F630). Protection of mice against lethality due to S. aureus strains Mn8 and Reynolds further showed that the backbone-specific MAb had optimal protective efficacy compared with the acetate-specific MAbs. These results provide evidence for the importance of epitope specificity in inducing the optimal protective antibody response to PNAG and indicate that MAbs to the deacetylated form of PNAG could be immunotherapeutic agents for preventing or treating staphylococcal infections.

scholarly journals Human monoclonal antibodies against Staphylococcus aureus surface antigens recognize in vitro biofilm and in vivo implant infections

2021 ◽  
Author(s):  
Lisanne de Vor ◽  
Bruce van Dijk ◽  
Kok P.M. van Kessel ◽  
Jeffrey S. Kavanaugh ◽  
Carla J.C. de Haas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Monoclonal Antibodies ◽  
Biofilm Formation ◽  
Teichoic Acid ◽  
Human Monoclonal Antibodies ◽  
Human Mabs ◽  
Wall Teichoic Acid ◽  
Alternative Approach

AbstractImplant-associated Staphylococcus aureus infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and/or treatment of biofilm-related infections. Here we show that mAbs targeting common surface components of S. aureus can recognize clinically relevant biofilm types. We identify two groups of antibodies: one group that uniquely binds S. aureus in biofilm state and one that recognizes S. aureus in both biofilm and planktonic state. In a mouse model, we show that mAb 4497 (recognizing wall teichoic acid (WTA)) specifically localizes to biofilm-infected implants. In conclusion, we demonstrate the capacity of several human mAbs to detect S. aureus biofilms in vitro and in vivo. This is an important first step to develop mAbs for imaging or treating S. aureus biofilms.

scholarly journals Human monoclonal antibodies against Staphylococcus aureus surface antigens recognize in vitro and in vivo biofilm

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Lisanne de Vor ◽  
Bruce van Dijk ◽  
Kok van Kessel ◽  
Jeffrey S Kavanaugh ◽  
Carla de Haas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Monoclonal Antibodies ◽  
Teichoic Acid ◽  
Human Monoclonal Antibodies ◽  
Human Mabs ◽  
Wall Teichoic Acid ◽  
Prosthetic Joint ◽  
Alternative Approach

Implant-associated Staphylococcus aureus infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and potential treatment of biofilm-related infections. Here, we show that mAbs targeting common surface components of S. aureus can recognize clinically relevant biofilm types. The mAbs were also shown to bind a collection of clinical isolates derived from different biofilm-associated infections (endocarditis, prosthetic joint, catheter). We identify two groups of antibodies: one group that uniquely binds S. aureus in biofilm state and one that recognizes S. aureus in both biofilm and planktonic state. Furthermore, we show that a mAb recognizing wall teichoic acid (clone 4497) specifically localizes to a subcutaneously implanted pre-colonized catheter in mice. In conclusion, we demonstrate the capacity of several human mAbs to detect S. aureus biofilms in vitro and in vivo.

scholarly journals Fc-Independent Protection from SARS-CoV-2 Infection by Recombinant Human Monoclonal Antibodies

Antibodies ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 45
Author(s):  
Tal Noy-Porat ◽  
Avishay Edri ◽  
Ron Alcalay ◽  
Efi Makdasi ◽  
David Gur ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Complement System ◽  
Neutralizing Antibodies ◽  
Human Monoclonal Antibodies ◽  
Antibody Treatment ◽  
Future Design ◽  
The Complement System

The use of passively-administered neutralizing antibodies is a promising approach for the prevention and treatment of SARS-CoV-2 infection. Antibody-mediated protection may involve immune system recruitment through Fc-dependent activation of effector cells and the complement system. However, the role of Fc-mediated functions in the efficacious in-vivo neutralization of SARS-CoV-2 is not yet clear, and it is of high importance to delineate the role this process plays in antibody-mediated protection. Toward this aim, we have chosen two highly potent SARS-CoV-2 neutralizing human monoclonal antibodies, MD65 and BLN1 that target distinct domains of the spike (RBD and NTD, respectively). The Fc of these antibodies was engineered to include the triple mutation N297G/S298G/T299A that eliminates glycosylation and the binding to FcγR and to the complement system activator C1q. As expected, the virus neutralization activity (in-vitro) of the engineered antibodies was retained. To study the role of Fc-mediated functions, the protective activity of these antibodies was tested against lethal SARS-CoV-2 infection of K18-hACE2 transgenic mice, when treatment was initiated either before or two days post-exposure. Antibody treatment with both Fc-variants similarly rescued the mice from death reduced viral load and prevented signs of morbidity. Taken together, this work provides important insight regarding the contribution of Fc-effector functions in MD65 and BLN1 antibody-mediated protection, which should aid in the future design of effective antibody-based therapies.

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

scholarly journals The Role of Monoclonal Antibodies in Smoldering and Newly Diagnosed Transplant-Eligible Multiple Myeloma

2020 ◽  
Vol 13 (12) ◽  
pp. 451
Author(s):  
Elena Zamagni ◽  
Paola Tacchetti ◽  
Paola Deias ◽  
Francesca Patriarca
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Survival Outcomes ◽  
Newly Diagnosed ◽  
Cellular Targets ◽  
Recent Introduction

The recent introduction of monoclonal antibodies (MoAbs), with several cellular targets, such as CD-38 (daratumumab and isatuximab) and SLAM F7 (elotuzumab), differently combined with other classes of agents, has significantly extended the outcomes of patients with multiple myeloma (MM) in different phases of the disease. Initially used in advanced/refractory patients, different MoAbs combination have been introduced in the treatment of newly diagnosed transplant eligible patients (NDTEMM), showing a significant improvement in the depth of the response and in survival outcomes, without a significant price in terms of toxicity. In smoldering MM, MoAbs have been applied, either alone or in combination with other drugs, with the goal of delaying the progression to active MM and restoring the immune system. In this review, we will focus on the main results achieved so far and on the main on-going trials using MoAbs in SMM and NDTEMM.

Simultaneous exposure to intracellular and extracellular photosensitizers for the treatment of Staphylococcus aureus infections

2021 ◽  
Author(s):  
Sydney L. Drury ◽  
Anderson R. Miller ◽  
Clare L. Laut ◽  
Alec B. Walter ◽  
Monique R. Bennett ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Near Infrared ◽  
Antimicrobial Photodynamic Therapy ◽  
Biological Processes ◽  
Drug Resistant ◽  
Soft Tissue Infections ◽  
Positive Bacterium ◽  
Human Monoclonal Antibodies ◽  
Simultaneous Exposure

Staphylococcus aureus is a serious threat to public health due to the rise of antibiotic resistance in this organism, which can prolong or exacerbate skin and soft tissue infections (SSTIs). Methicillin-resistant S. aureus is a Gram-positive bacterium and a leading cause of SSTIs. As such, many efforts are underway to develop therapies that target essential biological processes in S. aureus . Antimicrobial photodynamic therapy is effective alternative to antibiotics, therefore we developed an approach to simultaneously expose S. aureus to intracellular and extracellular photoactivators. A near infrared photosensitizer was conjugated to human monoclonal antibodies (mAbs) that target the S. aureus Isd heme acquisition proteins. Additionally, the compound VU0038882 was developed to increase photoactivatable porphyrins within the cell. Combinatorial PDT treatment of drug-resistant S. aureus exposed to VU0038882 and conjugated anti-Isd mAbs proved to be an effective antibacterial strategy in vitro and in a murine model of SSTIs.

scholarly journals Modulation of Polymorphonuclear Cell Interleukin-8 Secretion by Human Monoclonal Antibodies to Type 8 Pneumococcal Capsular Polysaccharide

2003 ◽  
Vol 71 (12) ◽  
pp. 6775-6783 ◽  
Author(s):  
Tamika Burns ◽  
Zhaojing Zhong ◽  
Michael Steinitz ◽  
Liise-anne Pirofski
Keyword(s):  
Monoclonal Antibodies ◽  
Capsular Polysaccharide ◽  
Immunoglobulin M ◽  
Interleukin 8 ◽  
Blue Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Polymorphonuclear Cells ◽  
Human Monoclonal Antibodies ◽  
Classical Complement Pathway

ABSTRACT Pneumococcal capsular polysaccharide (PS) vaccines induce type-specific immunoglobulin M (IgM), IgG, and IgA. Type-specific IgG to the PS is sufficient to confer protection against the homologous serotype of the pneumococcus, but the efficacies of type-specific IgM and IgA are less well understood. We examined the in vitro activities and efficacies in mice of two human monoclonal antibodies (MAbs) to type 8 PS, NAD (IgA) and D11 (IgM). MAb-mediated opsonophagocytic killing was evaluated after coculture of type 8 pneumococci with human polymorphonuclear cells (PMNs), type-specific or control MAbs, and human complement sources. The effects of the MAbs on PMN interleukin-8 (IL-8) and IL-6 secretion were determined in supernatants from cocultures containing pneumococci and PMNs by enzyme-linked immunosorbent assay. MAb efficacy was determined in an intratracheal model of type 8 infection in mice with classical complement pathway deficiency. Both MAbs were protective in 100% of infected mice. Neither MAb promoted a significant amount of killing of type 8 pneumococci compared to its isotype control MAb. Both type-specific MAbs mediated complement-dependent modulation of PMN IL-8 secretion, with increased secretion at effector/target (E:T) ratios of 500:1 and 50:1 and reduced secretion at 1:5. Trypan blue staining revealed that PMNs cocultured with D11 were less viable at an E:T ratio of 1:5 than PMNs cocultured with the control MAb. PMN IL-6 secretion was increased by both type-specific and control MAbs. These results suggest that certain type-specific IgM and IgAs might contribute to host defense by modulation of the inflammatory response to pneumococci.

scholarly journals The Role of Micronutrients in Support of the Immune Response against Viral Infections

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3198 ◽  
Author(s):  
Francesco Pecora ◽  
Federica Persico ◽  
Alberto Argentiero ◽  
Cosimo Neglia ◽  
Susanna Esposito
Keyword(s):  
Fatty Acids ◽  
Immune Response ◽  
Immune System ◽  
Viral Infections ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Optimal Function ◽  
The Impact

Viral infections are a leading cause of morbidity and mortality worldwide, and the importance of public health practices including handwashing and vaccinations in reducing their spread is well established. Furthermore, it is well known that proper nutrition can help support optimal immune function, reducing the impact of infections. Several vitamins and trace elements play an important role in supporting the cells of the immune system, thus increasing the resistance to infections. Other nutrients, such as omega-3 fatty acids, help sustain optimal function of the immune system. The main aim of this manuscript is to discuss of the potential role of micronutrients supplementation in supporting immunity, particularly against respiratory virus infections. Literature analysis showed that in vitro and observational studies, and clinical trials, highlight the important role of vitamins A, C, and D, omega-3 fatty acids, and zinc in modulating the immune response. Supplementation with vitamins, omega 3 fatty acids and zinc appears to be a safe and low-cost way to support optimal function of the immune system, with the potential to reduce the risk and consequences of infection, including viral respiratory infections. Supplementation should be in addition to a healthy diet and fall within recommended upper safety limits set by scientific expert bodies. Therefore, implementing an optimal nutrition, with micronutrients and omega-3 fatty acids supplementation, might be a cost-effective, underestimated strategy to help reduce the burden of infectious diseases worldwide, including coronavirus disease 2019 (COVID-19).

scholarly journals Immunity to pathogenic free-living amoebae: role of cell-mediated immunity

1980 ◽  
Vol 29 (2) ◽  
pp. 408-410
Author(s):  
R T Cursons ◽  
T J Brown ◽  
E A Keys ◽  
K M Moriarty ◽  
D Till
Keyword(s):  
Immune System ◽  
Inhibition Test ◽  
Delayed Hypersensitivity ◽  
Cell Mediated Immunity ◽  
Pathogenic Species ◽  
Free Living

The role of cell-mediated immunity in defense against pathogenic free-living amoebae was examined. Both the in vitro macrophage inhibition test and the in vivo delayed hypersensitivity test showed responses to both heterologous and homologous antigens, although homologous systems were the most efficient. It is suggested that exposure to nonpathogenic species of free-living amoebae can stimulate the immune system to be effective against pathogenic species. The significance of cell-mediated immunity as a defense against invasion by pathogenic free-living amoebae is discussed.

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