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Immuno, Volume 3, Issue 3 (September 2023) – 5 articles

Cover Story (view full-size image): COVID-19 mortality and morbidity remain high. The role of common cold coronavirus (CCCoV) antibodies (Abs) in COVID-19 pathogenesis and immunity is still debated. To address this, we have conducted a single-site longitudinal serosurveillance study on a cohort of adult patients with acute respiratory failure. Our findings suggest that increased COVID-19 severity was not associated with higher CCCoV Ab levels. In contrast, reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/CCCoV Ab levels, advanced age, and the presence of comorbidities correlated with significantly higher mortality. Additionally, while the levels of CCCoV Ab were generally low in this cohort, their higher levels were associated with decreased COVID-19 prevalence and increased SARS-CoV-2 Ab responses suggestive of their protective role. View this paper

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12 pages, 1480 KiB

Open AccessReview

Monoclonal War: The Antibody Arsenal and Targets for Expanded Application

by Eric H. Rosenn, Mickael Benhaim, Allison Siegel, David A. Stein, Joseph S. Leonard, Erik Katcher, Dania Halperin and Zachary Mostel

Immuno 2023, 3(3), 346-357; https://doi.org/10.3390/immuno3030021 - 20 Sep 2023

Viewed by 1880

Abstract

Advancements in sequencing and screening technology have made monoclonal antibodies more accessible, cost-effective, and precise. These drugs effectively target pathogens and cancer cells and even regulate metabolic pathways by focusing on specific intermediates. Monoclonal antibodies play a key role in mitigating a rise in occupation-related cancers, neurodegenerative disorders, and multidrug-resistant organisms. Here, we review the origins, mechanisms, and applications of this important drug class and explore future avenues for research. Full article

(This article belongs to the Section Synthetic Immunity and Immune Engineering)

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16 pages, 4102 KiB

Open AccessArticle

Increased COVID-19 Mortality and Deficient SARS-CoV-2 Immune Response Are Not Associated with Higher Levels of Endemic Coronavirus Antibodies

by Bindu Adhikari, Eugene M. Oltz, Joseph S. Bednash, Jeffrey C. Horowitz, Joshua O. Amimo, Sergei A. Raev, Soledad Fernández, Mirela Anghelina, Shan-Lu Liu, Mark P. Rubinstein, Daniel M. Jones, Linda J. Saif and Anastasia N. Vlasova

Immuno 2023, 3(3), 330-345; https://doi.org/10.3390/immuno3030020 - 04 Sep 2023

Cited by 1 | Viewed by 3659

Abstract

The impact of pre-existing common cold coronavirus (CCCoV) antibodies (Abs) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and pathogenesis remains poorly defined. We evaluated these associations in a cohort of hospitalized patients with COVID-19 and respiratory failure of varying severity. Patients with respiratory failure from other causes (non-COVID-19) were evaluated as controls. We demonstrated a positive correlation between levels of CCCoV and SARS-CoV-2 Abs using CCCoV and SARS-CoV-2 N and S protein peptide-specific ELISA. Consistent with the above, moderately increased levels of CCCoV-specific Abs in non-COVID-19 vs. COVID-19 patients suggest potential protective effects. Further, higher SARS-CoV-2 N protein-specific and CCCoV Ab levels were observed among surviving vs. non-surviving COVID-19 positive patients. However, the highest SARS-CoV-2 N and S protein-specific IgG and IgA Ab levels were noted in the patients with the most severe clinical disease. Finally, advanced age, cancer and immunosuppression were associated with significantly higher mortality and reduced SARS-CoV-2 and CCCoV Ab levels. Thus, our data highlight that sufficient SARS-CoV-2 N protein-specific Ab responses improve clinical outcomes in severely ill COVID-19 patients. We also confirmed that pre-existing CCCoV-specific Abs do not inhibit the SARS-CoV-2 Ab response and may further reduce the prevalence and/or severity of COVID-19. Full article

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41 pages, 1736 KiB

Open AccessReview

Bone Marrow: The Central Immune System

by Volker Schirrmacher

Immuno 2023, 3(3), 289-329; https://doi.org/10.3390/immuno3030019 - 03 Aug 2023

Cited by 2 | Viewed by 5249

Abstract

Bone marrow is known as the site of hematopoiesis. What is not being described in textbooks of immunology is the fact that bone marrow is not only a generative, but also an antigen-responsive, immune organ. It is also a major storage site for antigen-specific memory B and T cells. That bone marrow is a priming site for T cell responses to blood borne antigens was discovered exactly 20 years ago. This review celebrates this important discovery. The review provides a number of examples of medical relevance of bone marrow as a central immune system, including cancer, microbial infections, autoimmune reactions, and bone marrow transplantation. Bone marrow mesenchymal stem cell-derived stromal cells provide distinct bone marrow niches for stem cells and immune cells. By transmitting anti-inflammatory dampening effects, facilitating wound healing and tissue regeneration mesenchymal stem cells contribute to homeostasis of bone and other tissues. Based on the evidence presented, the review proposes that bone marrow is a multifunctional and protective immune system. In an analogy to the central nervous system, it is suggested that bone marrow be designated as the central immune system. Full article

(This article belongs to the Section Cancer Immunology and Immunotherapy)

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16 pages, 4782 KiB

Open AccessArticle

CDX-585, a Bispecific Antibody with Dual Targeting of ILT4 and PD-1 Checkpoint Pathways

by Michael B. Murphy, Laura Vitale, Shukai Xia, Zeyu Peng, Thomas O’Neill, Jay Lillquist, Anna Wasiuk, Jeff Weidlick, Jenifer Widger, Laura Mills-Chen, Andrea Crocker, Colleen Patterson, James Boyer, April R. Baronas, Mingjiu Chen, Hugh M. Davis, Mark Ma, Joel Goldstein, Lawrence J. Thomas, Diego Alvarado, Henry C. Marsh and Tibor Keler Show full author list Hide full author list

Immuno 2023, 3(3), 273-288; https://doi.org/10.3390/immuno3030018 - 07 Jul 2023

Cited by 1 | Viewed by 2424

Abstract

Immunoglobulin-like transcript 4 (ILT4) is an immunosuppressive molecule predominantly expressed on myeloid cells. Recent studies combining ILT4 suppression with programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) blockade have shown promising signs of activity in immune checkpoint inhibitor refractory patients. We theorized that coupling ILT4 and PD-1/PD-L1 blockade in a bispecific antibody (bsAb) may provide greater immune activating properties than combining the individual mAbs due to enhanced bridging of APCs to T cells. To test this approach, we developed CDX-585, a tetravalent ILT4xPD-1 IgG1-scFv bsAb from novel PD-1 and ILT-4 mAbs. CDX-585 is a potent antagonist of both PD-1 and ILT4. CDX-585 promotes M1 macrophage polarization and enhances pro-inflammatory cytokine secretion in response to lipopolysaccharide or CD40 agonist mAb treatment. In mixed lymphocyte reaction (MLR) assays, CDX-585 is more potent than the combination of parental antibodies. In a humanized NCG mouse SK-MEL-5 tumor model, CDX-585 exhibits greater antitumor activity than the combination of parental mAbs. A pilot study of CDX-585 in cynomolgus macaques confirmed a mAb-like pharmacokinetic profile without noted toxicities. These studies demonstrate that CDX-585 effectively combines ILT4 and the PD-1 blockade into one molecule that is more potent than the combination of the parental antibodies, providing the rationale to advance this bsAb into clinical studies. Full article

(This article belongs to the Section Cancer Immunology and Immunotherapy)

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23 pages, 2498 KiB

Open AccessReview

The Importance of Neutrophils in Osteoarthritis: Current Concepts and Therapeutic Perspectives

by Yeganeh Mehrani, Rasool Rahimi Junqani, Solmaz Morovati, Hossein Mehrani, Negar Karimi and Samaneh Ghasemi

Immuno 2023, 3(3), 250-272; https://doi.org/10.3390/immuno3030017 - 05 Jul 2023

Cited by 2 | Viewed by 2672

Abstract

Osteoarthritis (OA) is the most common degenerative joint disease that causes chronic pain and disability. Different innate immune components, including macrophages, T cells, and neutrophils, participate in OA pathophysiology. Neutrophils are the most abundant circulating leukocytes with multiple specialized functions contributing to innate and adaptive immune functions. Although neutrophils produce proinflammatory cytokines and chemokines, reactive oxygen species (ROS), matrix-degrading enzymes, and neutrophil extracellular traps (NET) that promote joint degradation as the first recruit cells in an inflamed joint, these cells also play an important role in joint repair by regulating the immune response, releasing anti-inflammatory factors, and activating certain protective genes. In this review, various aspects of neutrophil biology, their role in inflammation and its association with OA, and possible therapeutic approaches to target neutrophils for the treatment of OA are described. Since neutrophils play a complex role in the pathophysiology of osteoarthritis, contributing to joint degradation as well as joint repair, targeting these cells is likely to pave the way for a potential therapeutic approach for the management of OA. Future studies are needed to investigate the use of targeted therapies to modulate neutrophil function and identify their subpopulations that are associated with osteoarthritis progression or response to treatment. Full article

(This article belongs to the Section Innate Immunity and Inflammation)

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