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Rotavirus P2-VP8* and P24-VP8* Intramuscular Vaccines Evaluated in Gn Pigs
Published in Lijuan Yuan, Vaccine Efficacy Evaluation, 2022
In general, the magnitude of protection provided by a parenteral vaccine against orally transmitted diseases varies depending upon the levels of protective antibodies induced by the vaccine (Offit and Clark, 1985). ∆VP8* subunit vaccines are reasonably immunogenic; to further increase the immunogenicity, Dr. Yasutaka Hoshino's team, the Rotavirus Vaccine Development Section in the Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, incorporated a universal T cell epitope in the construct creating the P2-VP8* vaccine candidate (Wen et al., 2014b). Selected T cell epitopes from tetanus toxoid (TT) have been extensively studied. They are shown to be widely recognized in association with a large number of MHC class II molecules and to be universally immunogenic in humans and mice (Kaumaya et al., 1993). The P2 universal CD4+T cell epitope (aa 830–844) was reported to enhance the immunogenicity of a synthetic peptide vaccine for malaria (Franke et al., 1997) as well as tandem copies of a rotavirus VP8 epitope (Kovacs-Nolan and Mine, 2006). In addition, the P2 has been proven to be as efficient as the whole TT molecule as a carrier without inducing epitope suppression (Kumar et al., 1992). The immunity enhancing effect of the TT P2 universal T cell epitope is thought to be due to an activation of specific T cells for the synthesis of certain cytokines that are necessary for T and B cell activation and interaction as well as proliferation (Zegers and Boersma in Zegers, 1995).
Immunomodulation in Gene Therapeutics
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Andreas Block, Susan S. Rich, Shu-Hsia Chen, Savio L. C. Woo
Tumor antigens are presented to the host immune system by two major mechanisms: major histocompatibility (MHC) class I and MHC class II antigen presentation [30]. Almost all cells present endogenous and viral peptides on the cell surface via MHC class I molecules after processing the proteins in the endoplasmic reticulum [31] and thereby signaling immune cells. A subset of cells utilizes lysosomes to process phagocytosed endogenous proteins. Those peptides are presented on the cell surface via MHC class II molecules [32,33]. The MHC class II molecules are expressed by macrophages and dendritic cells, dedicated antigen presenting cells (APCs), but also B cells and activated T cells [34,35]. Moreover, MHC class II expression can be induced in a variety of normal cells by interferon-γ [35]. More recently it has been demonstrated that some phagocytosed proteins can also be presented by MHC class I molecules [36].
Gene Therapy for Lung Cancer
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
Choon Taek Lee, David P. Carbone
The MHC is a region of highly polymorphic genes whose products are expressed on the surface of most cells. MHC class I molecules bind endogenously synthesized peptide fragments and present them on cell surface for recognition by the T-cell receptor (TCR) on CD8+ T cells. MHC class II molecules are primarily expressed on “professional antigen-presenting cells” such as macrophages and dendritic cells that are thought to be primarily responsible for binding peptide fragments derived from extracellular proteins and presenting them to T helper cells. This interaction induces the production of cytokines necessary for the expansion of cytotoxic effectors. MHC molecules therefore play a key role in all phases of the immune response. Tumor cells usually have some level of expression of MHC class I molecules on their surface, but in many tumor cells expression of MHC may be low.
Emergence of mRNA vaccines in the management of cancer
Published in Expert Review of Vaccines, 2023
Mohamad Irfan Mohamad Razif, Nabilah Nizar, Nur Hannah Zainal Abidin, Syasya Nasuha Muhammad Ali, Wan Nurul Najihah Wan Zarimi, Junaidi Khotib, Deny Susanti, Muhammad Taufiq Mohd Jailani, Muhammad Taher
The most crucial cells responsible to initiate the immune response are dendritic cells as the APCs. Initially, mRNA will be endocytosed into the cytoplasm following immunization and bind with the ribosomes in the APCs to initiate and complete the translation process [32]. When the tumor antigen protein has been synthesized, the proteasome will break down the protein into smaller peptides in the cytoplasm and enter the major histocompatibility complex (MHC) presentation cascade [5,32]. MHC will then transport and present the antigenic peptides to cytotoxic T cells on the cell membrane. MHC class I and MHC class II activate the CD8+ T cells and CD4+ T cells, respectively. Besides, dendritic cells also interact with B cells to induce antibody production by the release of antigen proteins from the APCs after they are synthesized. These proteins can be ingested by dendritic cells and presented to the helper T cells and B cells by MHC [32]. Additionally, helper T cells or CD4+ T cells have the ability to co-activate B cells that are specific for an antigen and induce a humoral immune response, while B cells that act as APCs can, in turn, activate CD4+ T cells after internalizing extracellular proteins and presenting on the B cells’ MHC class II (Figure 5).
Giant cell arteritis
Published in Postgraduate Medicine, 2023
In GCA, initial events of the vascular inflammatory response involve activation of dendritic cells present in the adventitia of normal arteries [39]. Activation occurs through pathogen or damage sensing receptors which produce chemokines that attract and retain the dendritic cells [40]. Once activated, dendritic cells process and present antigens and express activation markers, MHC class II and costimulatory molecules required for antigen presentation and T-cell activation. Immunoinhibitory checkpoints may be deficient in GCA allowing for unchecked T-cell activation [40–42]. In addition to other autoimmune conditions, GCA is described in cancer patients treated with immune checkpoint inhibitors confirming the pathogenesis of excessive T lymphocyte activation in this disease [43].
An evaluation of pembrolizumab for classical Hodgkin lymphoma
Published in Expert Review of Hematology, 2022
Farheen Manji, Rob C Laister, John Kuruvilla
In contrast, PD-L1 expression and MHC class II positivity on RS cells were predictive of more favorable outcomes in the Checkmate 205 trial of nivolumab for RR cHL [14]. In these patients, higher level 9p24.1 copy gain and PD-L1 expression on RS cells were associated with improved progression-free survival (PFS). Patients with MHC class II expression on RS cells were more likely to achieve a CR. While alterations in 9p24.1 were almost ubiquitous in a sample of 108 patients with cHL at diagnosis, amplification of 9p24.1 is associated with advanced stage disease and inferior PFS [7]. Additional biomarkers have been evaluated in other studies of ICIs in a wide variety of malignancies. These include tumor infiltrating lymphocytes (colorectal cancer, melanoma, and non-small cell lung cancer), mutational burden (melanoma), peripheral white cell counts (melanoma) and gene expression profiling (melanoma) [23]. At present, there are no prospectively validated biomarkers for pembrolizumab or other ICIs in RR-cHL but this remains an active field of study