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Nanomedicine Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Saima Zulfiqar, Zunaira Naeem, Shahzad Sharif, Ayoub Rashid Ch., M. Zia-Ul-Haq, Marius Moga
To achieve high dosage effects, lymph node targeting by vaccine adjuvants nanoparticles is the useful strategy while adjuvanticity is increased by targeting the DCs. In vivo research by using PLGA-calcium-phosphate nanoparticles combined with antigen and adjuvant combination revealed that improved antigen uptake, greater titers for antibody and APC activation enhanced the efficiency immunogenic response [172, 173]. Further studies showed T cells priming and efficient cross-presentation can be triggered by encapsulation of antigen-adjuvant resulting in co-localized compartments in the cells to activate the DCs [174, 175]. Another combination of PLGA nanoparticles with TLR4 and TLR7 molecular adjuvants synergistically activate the APCs to produce a long-lasting antigen response [176]. Codelivery of PLGA nanoparticles with immunoregulatory drugs (adjuvants) can induce antigen-specific peripheral response to tolerate the auto-reactive T cells thus, inhibiting the autoimmune response [177–182].
Order Picornavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Peacey et al. (2008) demonstrated that the vaccination of mice with the RHDV VLPs that were chemically conjugated with ovalbumin or with both ovalbumin-derived CD4 (OTII) and CD8 (OTI) epitopes delayed the growth of the aggressive B16.OVA melanoma in mice. Neither VLP.OTI nor VLP.OTII alone were capable of inhibiting tumor growth. Win et al. (2011) translated the observation of the VLP cross-presentation reported by Peacey et al. (2008) into a more relevant human system and subsequently characterized the pathways used by dendritic cells to endocytose the VLPs coupled to model antigens, process them into peptides, and cross-present them to antigen-specific CD8+ T cells. Furthermore, the authors explored the potential to utilize human tumor lysates as a source of undefined antigen to couple to the VLPs to induce tumor-specific CD8+ T-cell responses in vitro (Win et al. 2011). Thus, Win et al. (2012) conjugated the Mel888 melanoma lysates to the RHDV VLPs. The chimeric VLPs were able to induce specific immune responses toward tumor cells while negating the inhibitory effects of lysates delivered alone.
Role of dendritic cells in integrating immune responses to luminal antigens
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Brian L. Kelsall, Maria Rescigno
Immature DCs phagocytose antigen through scavenger, Fc, and C-type lectin-like receptors and capture antigens by endocytosis and micropinocytosis. In addition, DCs have a distinct endocytic system that promotes efficient capture, processing, and presentation of antigens via MHC I (cross-presentation) and MHC II antigens to CD8 and CD4 T cells, respectively.
Rs867228 in FPR1 accelerates the manifestation of luminal B breast cancer
Published in OncoImmunology, 2023
Vincent Carbonnier, Julie Le Naour, Thomas Bachelot, Erika Vacchelli, Fabrice André, Suzette Delaloge, Guido Kroemer
The knockout of the human FPR1 orthologue in mice, Fpr1, revealed a major defect in chemotherapy-induced immunosurveillance, meaning that mice lacking one or two alleles of Fpr1 were unable to control tumor growth upon chemotherapy with anthracyclines (such as mitoxantrone) alone or combination with cyclophosphamide.3,7 Exhaustive phenotyping of the tumor microenvironment, responding to chemotherapy in the context of Fpr1-proficient or -deficient immune systems, revealed that FPR1 is required for the function of dendritic cells (DCs), allowing them to approach dying cancer cells that release the FPR1 ligand annexin A1 (ANXA1) and then to engage in the cross-presentation of tumor-associated antigens.3,8In vitro experiments on peripheral blood mononuclear cells from human volunteers bearing rs867228 confirmed a similar loss-of-function phenotype in both heterozygosity and (more so) in homozygosity.3,9 Murine adoptive transfer experiments corroborated that the cell type critical for FPR1-dependent immunosurveillance are indeed DCs, likely of the conventional cDC1 phenotype.8 Altogether, these experiments established that FPR1 plays a cardinal role in the perception of immunogenic cell death, as it occurs in the context of anticancer chemotherapies.10,11
Preclinical developments in the delivery of protein antigens for vaccination
Published in Expert Opinion on Drug Delivery, 2023
Dylan A. Hendy, Alex Haven, Eric M. Bachelder, Kristy M. Ainslie
Vaccination is one of the major technological advancements in preventing the spread of infectious disease. Since the discovery of the smallpox vaccine in the late 1700s by Edward Jenner, researchers have strived to develop vaccines for many different emerging infectious diseases [1]. To understand the mechanism by which a vaccine function, it is important to understand what happens when a pathogen infects a host. When a virus or bacteria enters the body, it will begin to replicate either inside or outside a cell. Depending on whether pathogen proteins are intracellular or taken in extracellularly by antigen presenting cells (APCs), peptide antigens will be presented on either major histocompatibility complex I (MHC I) or MHC II, respectively [2]. However, this model is not always true. For example, antigen cross-presentation allows for endocytosed antigens to be presented on MHC I and vice versa, and the utilization of antigen cross presentation is an important consideration when designing effective vaccines. Simultaneously, the APCs will become activated by sensing pathogen associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). The antigen will then be presented as peptides to T-cells which will activate the T-cell with the help of co-stimulatory molecules such as CD80/86 which are upregulated through PRR activation. T-cells can then aid in the activation of the B-cells to produce antibodies against the pathogen or kill cells infected by the pathogen in the case of CD8 + T-cells [2].
Development of neoantigens: from identification in cancer cells to application in cancer vaccines
Published in Expert Review of Vaccines, 2022
Nasim Ebrahimi, Maryam Akbari, Masoud Ghanaatian, Parichehr Roozbahani moghaddam, Samaneh Adelian, Marziyeh Borjian Boroujeni, Elnaz Yazdani, Amirhossein Ahmadi, Michael R. Hamblin
Dendritic cells (DC) are considered as the most effective type of APCs. Antigens are taken up by DCs and are processed, presented in MHC molecules on the cell surfaces, stimulating the T cells’ response. However, Exogenous vaccine antigens must gain access to the endogenous MHCI presentation pathway of DCs to activate CD8+ cytotoxic T cell responses, a process known as antigen cross-presentation. The professional APCs, DCs, play a primary role in bridging the gap between adaptive and innate immunity. DCs are noted for their cross-presentation ability since they digest and present foreign antigens on MHCI molecules considerably more effectively than other phagocytes. The efficacy of CD8 + T cell priming by DCs, known as cross-priming, is determined by both antigen cross-presentation efficiency (the amount of MHCI/peptide complex on the cell surface) and DC maturation (expression levels of co-stimulatory molecules and cytokines). Cross-presentation is critical for activating T cell responses against tumor antigens. However, it is still unclear how exogenous antigens are processed inside DCs and presented on MHCI to CD8 + T lymphocytes [106].