Order Picornavirales
Paul Pumpens, Peter Pushko, Philippe Le Mercier in Virus-Like Particles, 2022
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.
Nanomedicine Against COVID-19
Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga in The Covid-19 Pandemic, 2023
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].
The Utility of Immunoglobulin Fusions in DNA Immunization
Maurizio Zanetti, J. Donald Capra in The Antibodies, 2002
CTLA4-Ig targeting can increase Ab and Th responses, but it neither increases nor decreases CTL responses at least in the two examples we have tested. These were against influenza hemagglutinin (PR8 strain) in H-2d mice [48] and the ovalbumin CTL epitope SIINFEKL in H-2b mice [47]. There have been several reports examining the mechanism of CTL induction after intramuscular DNA injection that indicate a role for cross-presentation of antigen [51] via bone marrow derived antigen presenting cells [52-55]. At present, the cross-presenting antigen presenting cell is believed to be a CD8 + dendritic cell [56] and the optimal antigen source is a cell-associated form [57]. Our targeting strategy of a secreted molecule (thus not cell-associated) may not affect these mechanisms of cross-presentation. In any case, DNA injections (e.g., of OVA in mice) already elicit strong CTL responses so that any enhancement in CTL induction by targeting may be difficult to show.
Combination treatment of advanced pancreatic cancer using novel vaccine and traditional therapies
Published in Expert Review of Anticancer Therapy, 2018
Hiroto Matsui, Shoichi Hazama, Yoshitaro Shindo, Hiroaki Nagano
Cancer expresses unique antigens and cancer vaccines target them. Cancer vaccines can be classified into several major categories: peptide-based vaccines, whole-tumor cell vaccines, and DC-based vaccines. Antigens presented to antigen presenting cells (APCs) differ according to their antigen forms. Short-peptides are directly presented on human leukocyte antigen (HLA) class I of APCs. On the other hand, long-peptides and proteins are captured by APCs, processed and presented. Antigen-derived DNA and mRNA are presented on HLA class I and class II when transfected into dendritic cells. As a result, CD4 + T cells are induced by antigen presentation, and CD8 + T cells are induced by cross-presentation. Then, CD8 + T cells can become activated cytotoxic T cells (CTLs) by helper action of CD4 + T cells (Figure 1.).
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].
T cells specific for a TAP-independent self-peptide remain naïve in tumor-bearing mice and are fully exploitable for therapy
Published in OncoImmunology, 2018
Elien M. Doorduijn, Marjolein Sluijter, Koen A. Marijt, Bianca J. Querido, Sjoerd H. van der Burg, Thorbald van Hall
To compare these data on LnB5tg T cells to other TCR tg CD8+ T cells in tumor models, we examined priming efficiency of pmel-1 T cells (specific for the gp100 melanocyte differentiation self-antigen) and OT-I T cells (specific for the OVA foreign antigen).16,17 Pmel-1 T cells were transferred in mice harbouring B16F10 melanomas and OT-I T cells were tested in B16F10 tumors with transgenic ovalbumin. In tumor-draining LN, a significantly increased frequency of transgenic pmel-1 T cells was observed compared with contralateral non-draining LN, coinciding with a modest increase of divided T cells, although tumor infiltration was modest (Fig. 3B). This is in line with recent data demonstrating cross-presentation of tumor antigens in the draining LN by host dendritic cells.18 In contrast, transfer of naïve OT-I cells in B16F10.OVA tumor-bearing mice resulted in strikingly high numbers of activated OT-I cells in the tumors, comprising up to 70% TCR transgenic OT-I cells (Fig. 3C). Apparently, the pmel and OT-I transgenic T cells were primed in the presence of a tumor, whereas the RMA-S tumor did not induce priming of naïve TEIPP T cells.
Related Knowledge Centers
- Adaptive Immune System
- Cancer Vaccine
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- Mhc Class I
- Mhc Class II
- Vaccination
- Dendritic Cell
- Antigen-Presenting Cell
- Mhc Class II
- Minor Histocompatibility Antigen