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https://www.readbyqxmd.com/read/28525893/rat-embryonic-fibroblasts-immortalized-by-mrps18-2-protein-are-target-for-nk-cells
#1
Muhammad Mushtaq, Pradeepa N Pangigadde, Suhas Darekar, Erik Dissen, Elena Kashuba
Overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts (REFs). The derived cells (18IM) expressed embryonic stem cell markers. Noteworthy, genes encoding the COX family proteins were up-regulated significantly. It is known that the COX family proteins are involved in the regulation of immune response.In the present work we demonstrate that 18IM cells behave like stem cells when subjected to directed differentiation in vitro. However, unlike stem cells, 18IM cells do not develop tumors in vivo, in SCID mice...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525755/antibodies-from-a-human-survivor-define-sites-of-vulnerability-for-broad-protection-against-ebolaviruses
#2
Anna Z Wec, Andrew S Herbert, Charles D Murin, Elisabeth K Nyakatura, Dafna M Abelson, J Maximilian Fels, Shihua He, Rebekah M James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R Bakken, Eileen Goodwin, Hannah L Turner, Rohit K Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R Lai, Laura M Walker, Andrew B Ward, John M Dye, Kartik Chandran, Zachary A Bornholdt
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28522991/brachyspira-hyodysenteriae-and-b-pilosicoli-proteins-recognized-by-sera-of-challenged-pigs
#3
Vanessa Casas, Arantza Rodríguez-Asiain, Roberto Pinto-Llorente, Santiago Vadillo, Montserrat Carrascal, Joaquin Abian
The spirochetes Brachyspira hyodysenteriae and B. pilosicoli are pig intestinal pathogens that are the causative agents of swine dysentery (SD) and porcine intestinal spirochaetosis (PIS), respectively. Although some inactivated bacterin and recombinant vaccines have been explored as prophylactic treatments against these species, no effective vaccine is yet available. Immunoproteomics approaches hold the potential for the identification of new, suitable candidates for subunit vaccines against SD and PIS. These strategies take into account the gene products actually expressed and present in the cells, and thus susceptible of being targets of immune recognition...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28522338/year-round-influenza-immunisation-during-pregnancy-in-nepal-a-phase-4-randomised-placebo-controlled-trial
#4
Mark C Steinhoff, Joanne Katz, Janet A Englund, Subarna K Khatry, Laxman Shrestha, Jane Kuypers, Laveta Stewart, Luke C Mullany, Helen Y Chu, Steven C LeClerq, Naoko Kozuki, Monica McNeal, Adriana M Reedy, James M Tielsch
BACKGROUND: Influenza immunisation during pregnancy is recommended but not widely implemented in some low-income regions. We assessed the safety and efficacy in mothers and infants of year-round maternal influenza immunisation in Nepal, where influenza viruses circulate throughout the year. METHODS: In this phase 4, randomised, placebo-controlled trial, we enrolled two consecutive sequential annual cohorts of pregnant women from the Sarlahi district in southern Nepal...
May 15, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28522213/harnessing-self-assembled-peptide-nanoparticles-in-epitope-vaccine-design
#5
REVIEW
Manica Negahdaripour, Nasim Golkar, Nasim Hajighahramani, Sedigheh Kianpour, Navid Nezafat, Younes Ghasemi
Vaccination has been one of the most successful breakthroughs in medical history. In recent years, epitope-based subunit vaccines have been introduced as a safer alternative to traditional vaccines. However, they suffer from limited immunogenicity. Nanotechnology has shown value in solving this issue. Different kinds of nanovaccines have been employed, among which virus-like nanoparticles (VLPs) and self-assembled peptide nanoparticles (SAPNs) seem very promising. Recently, SAPNs have attracted special interest due to their unique properties, including molecular specificity, biodegradability, and biocompatibility...
May 15, 2017: Biotechnology Advances
https://www.readbyqxmd.com/read/28522212/bioengineering-bacterial-outer-membrane-vesicles-as-vaccine-platform
#6
REVIEW
Matthias J H Gerritzen, Dirk E Martens, René H Wijffels, Leo van der Pol, Michiel Stork
Outer membrane vesicles (OMVs) are naturally non-replicating, highly immunogenic spherical nanoparticles derived from Gram-negative bacteria. OMVs from pathogenic bacteria have been successfully used as vaccines against bacterial meningitis and sepsis among others and the composition of the vesicles can easily be engineered. OMVs can be used as a vaccine platform by engineering heterologous antigens to the vesicles. The major advantages of adding heterologous proteins to the OMV are that the antigens retain their native conformation, the ability of targeting specific immune responses, and a single production process suffices for many vaccines...
May 15, 2017: Biotechnology Advances
https://www.readbyqxmd.com/read/28520789/antigen-specific-immunoglobulin-variable-region-sequencing-measures-humoral-immune-response-to-vaccination-in-the-equine-neonate
#7
Rebecca L Tallmadge, Steven C Miller, Stephen A Parry, Maria Julia B Felippe
The value of prophylactic neonatal vaccination is challenged by the interference of passively transferred maternal antibodies and immune competence at birth. Taken our previous studies on equine B cell ontogeny, we hypothesized that the equine neonate generates a diverse immunoglobulin repertoire in response to vaccination, independently of circulating maternal antibodies. In this study, equine neonates were vaccinated with 3 doses of keyhole limpet hemocyanin (KLH) or equine influenza vaccine, and humoral immune responses were assessed using antigen-specific serum antibodies and B cell Ig variable region sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28516165/host-and-pathogen-derived-adjuvant-coatings-on-protein-nanoparticle-vaccines
#8
Timothy Z Chang, Ishatou Diambou, Jong Rok Kim, Baozhong Wang, Julie A Champion
Nanoparticulate and molecular adjuvants have shown great efficacy in enhancing immune responses, and the immunogenic vaccines of the future will most likely contain both. To investigate the immunostimulatory effects of molecular adjuvants on nanoparticle vaccines, we have designed ovalbumin (OVA) protein nanoparticles coated with two different adjuvants-flagellin (FliC) and immunoglobulin M (IgM). These proteins, derived from Salmonella and mice, respectively, are representatives of pathogen- and host-derived molecules that can enhance immune responses...
March 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/28515133/development-of-a-novel-virus-like-particle-vaccine-platform-that-mimics-immature-form-of-alphavirus
#9
Akane Urakami, Atsuko Sakurai, Momoko Ishikawa, Moh Lan Yap, Yevel Flores-Garcia, Yasunari Haseda, Taiki Aoshi, Fidel P Zavala, Michael G Rossmann, Sachiko Kuno, Ryuji Ueno, Wataru Akahata
Virus-like particles (VLPs) are non-infectious multiprotein structures that are engineered to self-assemble from viral structural proteins. Here, we developed a novel VLP-based vaccine platform utilizing VLPs from the Chikungunya virus. We identified two regions within the envelope protein, a structural component of Chikungunya, where foreign antigens can be inserted without compromising VLP structure. Our VLP displays 480 copious copies of an inserted antigen on the VLP surface in a highly symmetric manner, thus capable of inducing strong immune responses against any inserted antigen...
May 17, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28514686/glycine-substitution-at-helix-to-coil-transitions-facilitates-the-structural-determination-of-a-stabilized-subtype-c-hiv-envelope-glycoprotein
#10
Javier Guenaga, Fernando Garces, Natalia de Val, Robyn L Stanfield, Viktoriya Dubrovskaya, Brett Higgins, Barbara Carrette, Andrew B Ward, Ian A Wilson, Richard T Wyatt
Advances in HIV-1 envelope glycoprotein (Env) design generate native-like trimers and high-resolution clade A, B, and G structures and elicit neutralizing antibodies. However, a high-resolution clade C structure is critical, as this subtype accounts for the majority of HIV infections worldwide, but well-ordered clade C Env trimers are more challenging to produce due to their instability. Based on targeted glycine substitutions in the Env fusion machinery, we defined a general approach that disfavors helical transitions leading to post-fusion conformations, thereby favoring the pre-fusion state...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28513561/the-effect-of-physicochemical-modification-on-the-function-of-antibodies-induced-by-anti-nicotine-vaccine-in-mice
#11
Jennifer M Thorn, Keshab Bhattacharya, Renata Crutcher, Justin Sperry, Colleen Isele, Barbara Kelly, Libbey Yates, James Zobel, Ningli Zhang, Heather L Davis, Michael J McCluskie
Smoking remains one of the major causes of morbidity and mortality worldwide. One approach to assisting smoking cessation is via anti-nicotine vaccines, composed of nicotine-like haptens conjugated to a carrier protein plus adjuvant(s). We have previously shown that the carrier, hapten, linker, hapten load, degree of conjugate aggregation, and presence of adducts can each influence the function (nicotine-binding capacity) of the antibody (Ab) induced. Herein, we extend those findings and show that tertiary structure is also critical to the induction of functional immune responses and that this can be influenced by conjugation conditions...
May 17, 2017: Vaccines
https://www.readbyqxmd.com/read/28512091/conformational-flexibility-in-the-immunoglobulin-like-domain-of-the-hepatitis-c-virus-glycoprotein-e2
#12
Ieva Vasiliauskaite, Ania Owsianka, Patrick England, Abdul Ghafoor Khan, Sarah Cole, Dorothea Bankwitz, Steven K H Foung, Thomas Pietschmann, Joseph Marcotrigiano, Felix A Rey, Arvind H Patel, Thomas Krey
The hepatitis C virus (HCV) glycoprotein E2 is the major target of neutralizing antibodies and is therefore highly relevant for vaccine design. Its structure features a central immunoglobulin (Ig)-like β-sandwich that contributes to the binding site for the cellular receptor CD81. We show that a synthetic peptide corresponding to a β-strand of this Ig-like domain forms an α-helix in complex with the anti-E2 antibody DAO5, demonstrating an inside-out flip of hydrophobic residues and a secondary structure change in the composite CD81 binding site...
May 16, 2017: MBio
https://www.readbyqxmd.com/read/28511994/study-of-rubella-candidate-vaccine-based-on-a-structurally-modified-plant-virus
#13
Ekaterina A Trifonova, Vladimir A Zenin, Nikolai A Nikitin, Maria S Yurkova, Ekaterina M Ryabchevskaya, Egor V Putlyaev, Ekaterina K Donchenko, Olga A Kondakova, Alexey N Fedorov, Joseph G Atabekov, Olga V Karpova
A novel rubella candidate vaccine based on a structurally modified plant virus - spherical particles (SPs) - was developed. SPs generated by the thermal remodelling of the tobacco mosaic virus are promising platforms for the development of vaccines. SPs combine unique properties: biosafety, stability, high immunogenicity and the effective adsorption of antigens. We assembled in vitro and characterised complexes (candidate vaccine) based on SPs and the rubella virus recombinant antigen. The candidate vaccine induced a strong humoral immune response against rubella...
May 13, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28511853/immunologic-evaluation-of-10-different-adjuvants-for-use-in-vaccines-for-chickens-against-highly-pathogenic-avian-influenza-virus
#14
Nazir Ahmed Lone, Erica Spackman, Darrell Kapczynski
Avian influenza viruses (AIV) are a threat to poultry production worldwide. Vaccination is utilized as a component of control programs for both high pathogenicity (HP) and low pathogenicity (LP) AIV. Over 95% of all AIV vaccine used in poultry are inactivated, adjuvanted products. To identify the best formulations for chickens, vaccines were prepared with beta-propiolactone (BPL) inactivated A/British Columbia/314514-1/2004 H7N3 LP AIV using ten commercially available or experimental adjuvants. Each vaccine formulation was evaluated for immunogenicity in chickens...
May 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28511142/tailoring-nanostructured-lipid-carriers-for-the-delivery-of-protein-antigens-physicochemical-properties-versus-immunogenicity-studies
#15
Thomas Courant, Emilie Bayon, Hei Lanne Reynaud-Dougier, Christian Villiers, Mathilde Menneteau, Patrice N Marche, Fabrice P Navarro
New vaccine formulations are still highly anticipated in the near-future to face incoming health challenges, such as emergence or reemergence of severe infectious diseases, immunosenescence associated with elderly or the spread of pathogens resistant to antibiotics. In particular, new nanoparticle-based adjuvants are promising for sub-unit vaccines in order to elicit potent and long lasting immune responses with a better control on their safety. In this context, an innovative delivery system of protein antigens has been designed based on the chemical grafting of the antigen onto the shell of Nanostructured Lipid Carriers (NLC)...
May 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28510418/conjugation-reaction-with-8-arm-peg-markedly-improves-the-immunogenicity-of-mycobacterium-tuberculosis-cfp10-tb10-4-fusion-protein
#16
Xiaowei Sun, Weili Yu, Quanhai Pang, Tao Hu
Mycobacterium tuberculosis (Mtb) is a serious fatal pathogen responsible for tuberculosis (TB). Effective vaccination is highly desired for immunoprotection against Mtb infection. CFP10 and TB10.4 are two important immunodominant Mtb-secreted protein antigens, which suffer from poor immunogenicity. Thus, an antigen delivery system and adjuvants are needed to improve the immunogenicity of the two proteins. CFP10 and TB10.4 are two Mtb-secreted immunodominant protein antigens. A CFP10-TB10.4 fusion protein (CT) was used as the antigen...
May 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28509875/in-silico-analysis-of-epitope-based-vaccine-candidates-against-hepatitis-b-virus-polymerase-protein
#17
Juzeng Zheng, Xianfan Lin, Xiuyan Wang, Liyu Zheng, Songsong Lan, Sisi Jin, Zhanfan Ou, Jinming Wu
Hepatitis B virus (HBV) infection has persisted as a major public health problem due to the lack of an effective treatment for those chronically infected. Therapeutic vaccination holds promise, and targeting HBV polymerase is pivotal for viral eradication. In this research, a computational approach was employed to predict suitable HBV polymerase targeting multi-peptides for vaccine candidate selection. We then performed in-depth computational analysis to evaluate the predicted epitopes' immunogenicity, conservation, population coverage, and toxicity...
May 16, 2017: Viruses
https://www.readbyqxmd.com/read/28509605/safety-and-immunogenicity-of-bio-pox%C3%A2-a-live-varicella-vaccine-oka-strain-in-indian-children-a-comparative-multicentric-randomized-phase-ii-iii-clinical-trial
#18
Anand Prakash Dubey, Mohammad Moonis Akbar Faridi, Monjori Mitra, Iqbal Rajinder Kaur, Aashima Dabas, Jaydeep Choudhury, Mallar Mukherjee, Devendra Mishra
Varicella or chickenpox is a highly contagious disease with a high secondary attack rate. Almost 30% of Indian adolescents lack protective antibodies against varicella, emphasising the need of routine varicella immunization. The Oka VZV is a well-established, safe and efficacious vaccine strain that is highly immunogenic and produces lifelong protective immunity. The present multicentric, open label, randomized, controlled Phase II/III study, compared the Bio Pox™ (indigenous investigational vaccine) with a licensed vaccine, Varivax™, for its safety and immunogenicity profile in 252 healthy subjects in the age group of 1-12 years (cohort I: 6-12 years, II:1-6 years) in three tertiary medical institutions...
May 16, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28507809/t-cell-therapy-targeting-a-public-neoantigen-in-microsatellite-instable-colon-cancer-reduces-in-vivo-tumor-growth
#19
Else M Inderberg, Sébastien Wälchli, Marit R Myhre, Sissel Trachsel, Hilde Almåsbak, Gunnar Kvalheim, Gustav Gaudernack
T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to limit the risk of off-target toxicity. Directing T cells against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative to tumor-associated self-antigens. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507029/cd63-mediated-antigen-delivery-into-extracellular-vesicles-via-dna-vaccination-results-in-robust-cd8-t-cell-responses
#20
Tomohiro Kanuma, Takuya Yamamoto, Kouji Kobiyama, Eiko Moriishi, Yuji Masuta, Takato Kusakabe, Koji Ozasa, Etsushi Kuroda, Nao Jounai, Ken J Ishii
DNA vaccines are attractive immunogens for priming humoral and cellular immune responses to the encoded Ag. However, their ability to induce Ag-specific CD8(+) T cell responses requires improvement. Among the strategies for improving DNA vaccine immunogenicity are booster vaccinations, alternate vaccine formulations, electroporation, and genetic adjuvants, but few, such as extracellular vesicles (EVs), target natural Ag delivery systems. By focusing on CD63, a tetraspanin protein expressed on various cellular membranes, including EVs, we examined whether a DNA vaccine encoding an Ag fused to CD63 delivered into EVs would improve vaccine immunogenicity...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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