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Vaccines

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https://www.readbyqxmd.com/read/27929422/co-administration-of-lipid-nanoparticles-and-sub-unit-vaccine-antigens-is-required-for-increase-in-antigen-specific-immune-responses-in-mice
#1
Elizabeth A Thoryk, Gokul Swaminathan, Steven Meschino, Kara S Cox, Marian Gindy, Danilo R Casimiro, Andrew J Bett
A vast body of evidence suggests that nanoparticles function as potent immune-modulatory agents. We have previously shown that Merck proprietary Lipid NanoParticles (LNPs) markedly boost B-cell and T-cell responses to sub-unit vaccine antigens in mice. To further evaluate the specifics of vaccine delivery and dosing regimens in vivo, we performed immunogenicity studies in BALB/c and C57BL/6 mice using two model antigens, Hepatitis B Surface Antigen (HBsAg) and Ovalbumin (OVA), respectively. To assess the requirement for co-administration of antigen and LNP for the elicitation of immune responses, we evaluated immune responses after administering antigen and LNP to separate limbs, or administering antigen and LNP to the same limb but separated by 24 h...
December 6, 2016: Vaccines
https://www.readbyqxmd.com/read/27929420/tumor-microenvironment-metabolism-a-new-checkpoint-for-anti-tumor-immunity
#2
REVIEW
Nicole E Scharping, Greg M Delgoffe
When a T cell infiltrates a tumor, it is subjected to a variety of immunosuppressive and regulatory signals in the microenvironment. However, it is becoming increasingly clear that due to the proliferative and energetically-deregulated nature of tumor cells, T cells also operate at a metabolic disadvantage. The nutrient dearth of the tumor microenvironment (TME) creates "metabolic checkpoints" upon infiltrating T cells, impacting their ability to survive, proliferate and function effectively. In this review, we summarize the basics of tumor cell and T cell metabolism and discuss recent advances elucidating the individual metabolic checkpoints exerted on T cells that drive their dysfunction in the TME...
December 6, 2016: Vaccines
https://www.readbyqxmd.com/read/27918420/synthetic-biodegradable-microparticle-and-nanoparticle-vaccines-against-the-respiratory-syncytial-virus
#3
REVIEW
Patricia A Jorquera, Ralph A Tripp
Synthetic biodegradable microparticle and nanoparticle platform technology provides the opportunity to design particles varying in composition, size, shape and surface properties for application in vaccine development. The use of particle vaccine formulations allows improvement of antigen stability and immunogenicity while allowing targeted delivery and slow release. This technology has been design to develop novel vaccines against the respiratory syncytial virus (RSV), the leading cause of lower respiratory tract infection in infants...
December 2, 2016: Vaccines
https://www.readbyqxmd.com/read/27869670/homologous-prime-boost-vaccination-with-ova-entrapped-in-self-adjuvanting-archaeosomes-induces-high-numbers-of-ova-specific-cd8%C3%A2-%C2%BA-t-cells-that-protect-against-subcutaneous-b16-ova-melanoma
#4
Felicity C Stark, Michael J McCluskie, Lakshmi Krishnan
Homologous prime-boost vaccinations with live vectors typically fail to induce repeated strong CD8⁺ T cell responses due to the induction of anti-vector immunity, highlighting the need for alternative delivery vehicles. The unique ether lipids of archaea may be constituted into liposomes, archaeosomes, which do not induce anti-carrier responses, making them an ideal candidate for use in repeat vaccination systems. Herein, we evaluated in mice the maximum threshold of antigen-specific CD8⁺ T cell responses that may be induced by multiple homologous immunizations with ovalbumin (OVA) entrapped in archaeosomes derived from the ether glycerolipids of the archaeon Methanobrevibacter smithii (MS-OVA)...
November 17, 2016: Vaccines
https://www.readbyqxmd.com/read/27854240/the-impact-of-chemotherapy-radiation-and-epigenetic-modifiers-in-cancer-cell-expression-of-immune-inhibitory-and-stimulatory-molecules-and-anti-tumor-efficacy
#5
REVIEW
Jessica Ann Chacon, Keith Schutsky, Daniel J Powell
Genomic destabilizers, such as radiation and chemotherapy, and epigenetic modifiers are used for the treatment of cancer due to their apoptotic effects on the aberrant cells. However, these therapies may also induce widespread changes within the immune system and cancer cells, which may enable tumors to avoid immune surveillance and escape from host anti-tumor immunity. Genomic destabilizers can induce immunogenic death of tumor cells, but also induce upregulation of immune inhibitory ligands on drug-resistant cells, resulting in tumor progression...
November 14, 2016: Vaccines
https://www.readbyqxmd.com/read/27834857/the-cd8%C3%A2-%C2%BA-t-cell-mediated-immunity-induced-by-hpv-e6-uploaded-in-engineered-exosomes-is-improved-by-iscomatrix-tm-adjuvant
#6
Francesco Manfredi, Paola di Bonito, Barbara Ridolfi, Simona Anticoli, Claudia Arenaccio, Chiara Chiozzini, Adriana Baz Morelli, Maurizio Federico
We recently described the induction of an efficient CD8⁺ T cell-mediated immune response against a tumor-associated antigen (TAA) uploaded in engineered exosomes used as an immunogen delivery tool. This immune response cleared tumor cells inoculated after immunization, and controlled the growth of tumors implanted before immunization. We looked for new protocols aimed at increasing the CD8⁺ T cell specific response to the antigen uploaded in engineered exosomes, assuming that an optimized CD8⁺ T cell immune response would correlate with a more effective depletion of tumor cells in the therapeutic setting...
November 9, 2016: Vaccines
https://www.readbyqxmd.com/read/27834810/mesenchymal-stromal-cells-can-regulate-the-immune-response-in-the-tumor-microenvironment
#7
REVIEW
Alessandro Poggi, Massimo Giuliani
The tumor microenvironment is a good target for therapy in solid tumors and hematological malignancies. Indeed, solid tumor cells' growth and expansion can influence neighboring cells' behavior, leading to a modulation of mesenchymal stromal cell (MSC) activities and remodeling of extracellular matrix components. This leads to an altered microenvironment, where reparative mechanisms, in the presence of sub-acute inflammation, are not able to reconstitute healthy tissue. Carcinoma cells can undergo epithelial mesenchymal transition (EMT), a key step to generate metastasis; these mesenchymal-like cells display the functional behavior of MSC...
November 8, 2016: Vaccines
https://www.readbyqxmd.com/read/27827990/edwardsiella-tarda-ompa-encapsulated-in-chitosan-nanoparticles-shows-superior-protection-over-inactivated-whole-cell-vaccine-in-orally-vaccinated-fringed-lipped-peninsula-carp-labeo-fimbriatus
#8
Saurabh Dubey, Kiran Avadhani, Srinivas Mutalik, Sangeetha Madambithara Sivadasan, Biswajit Maiti, Shivani Kallappa Girisha, Moleyur Nagarajappa Venugopal, Stephen Mutoloki, Øystein Evensen, Indrani Karunasagar, Hetron Mweemba Munang’andu
The use of oral vaccination in finfish has lagged behind injectable vaccines for a long time as oral vaccines fall short of injection vaccines in conferring protective immunity. Biodegradable polymeric nanoparticles (NPs) have shown potential to serve as antigen delivery systems for oral vaccines. In this study the recombinant outer membrane protein A (rOmpA) of Edwardsiella tarda was encapsulated in chitosan NPs (NP-rOmpA) and used for oral vaccination of Labeo fimbriatus. The rOmpA purity was 85%, nanodiameter <500 nm, encapsulation efficiency 60...
November 7, 2016: Vaccines
https://www.readbyqxmd.com/read/27827980/replicon-rna-viral-vectors-as-vaccines
#9
REVIEW
Kenneth Lundstrom
Single-stranded RNA viruses of both positive and negative polarity have been used as vectors for vaccine development. In this context, alphaviruses, flaviviruses, measles virus and rhabdoviruses have been engineered for expression of surface protein genes and antigens. Administration of replicon RNA vectors has resulted in strong immune responses and generation of neutralizing antibodies in various animal models. Immunization of mice, chicken, pigs and primates with virus-like particles, naked RNA or layered DNA/RNA plasmids has provided protection against challenges with lethal doses of infectious agents and administered tumor cells...
November 7, 2016: Vaccines
https://www.readbyqxmd.com/read/27827921/targeting-immune-regulatory-networks-to-counteract-immune-suppression-in-cancer
#10
REVIEW
Chiara Camisaschi, Viviana Vallacchi, Elisabetta Vergani, Marcella Tazzari, Simona Ferro, Alessandra Tuccitto, Olga Kuchuk, Eriomina Shahaj, Roberta Sulsenti, Chiara Castelli, Monica Rodolfo, Licia Rivoltini, Veronica Huber
The onset of cancer is unavoidably accompanied by suppression of antitumor immunity. This occurs through mechanisms ranging from the progressive accumulation of regulatory immune cells associated with chronic immune stimulation and inflammation, to the expression of immunosuppressive molecules. Some of them are being successfully exploited as therapeutic targets, with impressive clinical results achieved in patients, as in the case of immune checkpoint inhibitors. To limit immune attack, tumor cells exploit specific pathways to render the tumor microenvironment hostile for antitumor effector cells...
November 4, 2016: Vaccines
https://www.readbyqxmd.com/read/27827885/is-there-still-room-for-cancer-vaccines-at-the-era-of-checkpoint-inhibitors
#11
REVIEW
Soumaya Karaki, Marie Anson, Thi Tran, Delphine Giusti, Charlotte Blanc, Stephane Oudard, Eric Tartour
Checkpoint inhibitor (CPI) blockade is considered to be a revolution in cancer therapy, although most patients (70%-80%) remain resistant to this therapy. It has been hypothesized that only tumors with high mutation rates generate a natural antitumor T cell response, which could be revigorated by this therapy. In patients with no pre-existing antitumor T cells, a vaccine-induced T cell response is a rational option to counteract clinical resistance. This hypothesis has been validated in preclinical models using various cancer vaccines combined with inhibitory pathway blockade (PD-1-PDL1-2, CTLA-4-CD80-CD86)...
November 3, 2016: Vaccines
https://www.readbyqxmd.com/read/27827871/the-role-of-myeloid-derived-suppressor-cells-mdsc-in-cancer-progression
#12
REVIEW
Viktor Umansky, Carolin Blattner, Christoffer Gebhardt, Jochen Utikal
The immunosuppressive tumor microenvironment represents not only one of the key factors stimulating tumor progression but also a strong obstacle for efficient tumor immunotherapy. Immunosuppression was found to be associated with chronic inflammatory mediators including cytokines, chemokines and growth factors produced by cancer and stroma cells. Long-term intensive production of these factors induces the formation of myeloid-derived suppressor cells (MDSCs) representing one of the most important players mediating immunosuppression...
November 3, 2016: Vaccines
https://www.readbyqxmd.com/read/27775593/tumor-derived-exosomes-and-their-role-in-tumor-induced-immune-suppression
#13
Theresa L Whiteside
Tumor-derived exosomes (TEX) are emerging as critical components of an intercellular information network between the tumor and the host. The tumor escapes from the host immune system by using a variety of mechanisms designed to impair or eliminate anti-tumor immunity. TEX carrying a cargo of immunoinhibitory molecules and factors represent one such mechanism. TEX, which are present in all body fluids of cancer patients, deliver negative molecular or genetic signals to immune cells re-programming their functions...
October 20, 2016: Vaccines
https://www.readbyqxmd.com/read/27754364/in%C3%AF-uenza-and-memory-t-cells-how-to-awake-the-force
#14
Jan Spitaels, Kenny Roose, Xavier Saelens
Annual influenza vaccination is an effective way to prevent human influenza. Current vaccines are mainly focused on eliciting a strain-matched humoral immune response, requiring yearly updates, and do not provide protection for all vaccinated individuals. The past few years, the importance of cellular immunity, and especially memory T cells, in long-lived protection against influenza virus has become clear. To overcome the shortcomings of current influenza vaccines, eliciting both humoral and cellular immunity is imperative...
October 13, 2016: Vaccines
https://www.readbyqxmd.com/read/27754314/biodegradable-polymeric-nanoparticles-based-vaccine-adjuvants-for-lymph-nodes-targeting
#15
Alice Gutjahr, Capucine Phelip, Anne-Line Coolen, Claire Monge, Anne-Sophie Boisgard, Stéphane Paul, Bernard Verrier
Vaccines have successfully eradicated a large number of diseases. However, some infectious diseases (such as HIV, Chlamydia trachomatis or Bacillus anthracis) keep spreading since there is no vaccine to prevent them. One way to overcome this issue is the development of new adjuvant formulations which are able to induce the appropriate immune response without sacrificing safety. Lymph nodes are the site of lymphocyte priming by antigen-presenting cells and subsequent adaptive immune response, and are a promising target for vaccine formulations...
October 12, 2016: Vaccines
https://www.readbyqxmd.com/read/27626449/ag85a-dna-vaccine-delivery-by-nanoparticles-influence-of-the-formulation-characteristics-on-immune-responses
#16
Johanna Poecheim, Christophe Barnier-Quer, Nicolas Collin, Gerrit Borchard
The influence of DNA vaccine formulations on immune responses in combination with adjuvants was investigated with the aim to increase cell-mediated immunity against plasmid DNA (pDNA) encoding Mycobacterium tuberculosis antigen 85A. Different ratios of pDNA with cationic trimethyl chitosan (TMC) nanoparticles were characterized for their morphology and physicochemical characteristics (size, zeta potential, loading efficiency and pDNA release profile) applied in vitro for cellular uptake studies and in vivo, to determine the dose-dependent effects of pDNA on immune responses...
September 12, 2016: Vaccines
https://www.readbyqxmd.com/read/27618112/neutrophils-and-granulocytic-mdsc-the-janus-god-of-cancer-immunotherapy
#17
REVIEW
Serena Zilio, Paolo Serafini
Neutrophils are the most abundant circulating blood cell type in humans, and are the first white blood cells recruited at the inflammation site where they orchestrate the initial immune response. Although their presence at the tumor site was recognized in the 1970s, until recently these cells have been neglected and considered to play just a neutral role in tumor progression. Indeed, in recent years neutrophils have been recognized to play a dual role in tumor development by either assisting the growth, angiogenesis, invasion, and metastasis or by exerting tumoricidal action directly via the secretion of antitumoral compounds, or indirectly via the orchestration of antitumor immunity...
September 9, 2016: Vaccines
https://www.readbyqxmd.com/read/27608046/t-regulatory-cells-and-vaccination-pay-attention-and-do-not-neglect-them-lessons-from-hiv-and-cancer-vaccine-trials
#18
REVIEW
Vedran Brezar, Véronique Godot, Liang Cheng, Lishan Su, Yves Lévy, Nabila Seddiki
Efficient vaccines are characterized by the establishment of long-lived memory T cells, including T-helper (effectors and follicular) and T-regulatory cells (Tregs). While the former induces cytotoxic or antibody responses, the latter regulates immune responses by maintaining homeostasis. The role of Tregs in inflammatory conditions is ambiguous and their systematic monitoring in vaccination along with effector T-cells is not instinctive. Recent studies from the cancer field clearly showed that Tregs suppress vaccine-induced immune responses and correlate with poor clinical benefit...
September 5, 2016: Vaccines
https://www.readbyqxmd.com/read/27598210/monitoring-of-the-immune-dysfunction-in-cancer-patients
#19
REVIEW
Saskia J A M Santegoets, Marij J P Welters, Sjoerd H van der Burg
Immunotherapy shows promising clinical results in patients with different types of cancer, but its full potential is not reached due to immune dysfunction as a result of several suppressive mechanisms that play a role in cancer development and progression. Monitoring of immune dysfunction is a prerequisite for the development of strategies aiming to alleviate cancer-induced immune suppression. At this point, the level at which immune dysfunction occurs has to be established, the underlying mechanism(s) need to be known, as well as the techniques to assess this...
September 2, 2016: Vaccines
https://www.readbyqxmd.com/read/27509527/regulatory-t-cells-in-the-tumor-microenvironment-and-cancer-progression-role-and-therapeutic-targeting
#20
REVIEW
Belal Chaudhary, Eyad Elkord
Recent years have seen significant efforts in understanding and modulating the immune response in cancer. In this context, immunosuppressive cells, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), have come under intense investigation for their proposed roles in suppressing tumor-specific immune responses and establishing an immunosuppressive tumor microenvironment, thus enabling tumor immune evasion. Additionally, recent evidence indicates that Tregs comprise diverse and heterogeneous subsets; phenotypically and functionally distinct subsets of tumor-infiltrating Tregs could contribute differently to cancer prognosis and clinical outcomes...
August 6, 2016: Vaccines
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