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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.
Mucosal immune responses to microbes in genital tract
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Upon natural infection with HPV, only poor immune responses develop. This is owing to the ability of the virus to evade immunity by several mechanisms: (1) HPV E6 protein causes the depletion of Langerhans cells; (2) HPV E5 protein downregulates MHC I expression; and (3) HPV E7 protein blocks type I IFN signaling. Thus, activation of CD8+ T-cell immunity to HPV requires cross-presentation of infected cells by noninfected DCs. Although the nature of the DCs that are responsible for this cross-priming is unknown, because HPV infection occurs only within the stratified squamous epithelial layer, Langerhans cells within the epithelial layer, and possibly submucosal DCs that extend their dendrites, are most likely the ones participating in this process. HPV infection results in the induction of antibody and T-cell responses. Since the majority of HPV infections are cleared within 2 years, and because HIV infection results in an increased prevalence of HPV infections, it is likely that naturally induced immune responses are responsible for controlling HPV infection in most cases. It is noteworthy that neutralizing antibodies induced by HPV vaccines are remarkably efficient in preventing infection by HPV, as discussed later.
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].
Dendritic cells in COVID-19 immunopathogenesis: insights for a possible role in determining disease outcome
Published in International Reviews of Immunology, 2021
Rodrigo Cerqueira Borges, Miriam Sayuri Hohmann, Sergio Marques Borghi
Important innate defenses provided by dendritic cells are related to the production of immune-enhancing cytokines, e.g. interleukin (IL)-12 and type I IFNs, and the mobilization of innate lymphocytes [natural killer (NK)], NKT, and γσT). Although dendritic cells have phagocytic properties, uptake of particles can be limited and not known to contribute to microbial clearance and killing. Nevertheless, their phagocytic capacity is efficient for antigen processing and presentation on MHC I and II [46]. Dendritic cells constitutively express MHC II, as well as co-stimulatory molecules, and possess efficient migratory capacity, thus being considered a determinant cell for immunity against pathogens [47]. Some specialized dendritic cells can also present exogenous antigens onto the MHC I to activate CD8+ T cells though the process of cross-presentation [48]. Thus, dendritic cells provide an important link between the innate and adaptive immune response.