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https://www.readbyqxmd.com/read/28106117/norovirus-p-particle-based-active-a%C3%AE-immunotherapy-elicits-sufficient-immunogenicity-and-improves-cognitive-capacity-in-a-mouse-model-of-alzheimer-s-disease
#1
Lu Fu, Yingnan Li, Yue Hu, Yayuan Zheng, Bin Yu, Haihong Zhang, Jiaxin Wu, Hui Wu, Xianghui Yu, Wei Kong
Disease-modifying immunotherapies focusing on reducing amyloid-beta (Aβ) deposition are the main treatment for Alzheimer's disease (AD). However, none of the Aβ immunotherapies has produced clinically meaningful results to date. The main reason for this lack of efficacy is that the vaccine induces insufficiently high antibody titers, as it contains small B-cell epitope of Aβ to avoid Aβ42-specific T-cell activation. With the aim of generating a potent AD vaccine, we designed the protein PP-3copy-Aβ1-6-loop123, comprising three copies of Aβ1-6 inserted into three loops of a novel vaccine platform, the norovirus P particle, which could present Aβ at its surface and remarkably enhance the immunogenicity of the vaccine...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28103328/a-pre-clinical-safety-evaluation-of-sbp-hbsag-binding-protein-adjuvant-for-hepatitis-b-vaccine
#2
Jingbo Wang, Caixia Su, Rui Liu, Baoxiu Liu, Inam Ullah Khan, Jun Xie, Naishuo Zhu
Although adjuvants are a common component of many vaccines, there are few adjuvants licensed for use in humans due to concerns about their toxic effects. There is a need to develop new and safe adjuvants, because some existing vaccines have low immunogenicity among certain patient groups. In this study, SBP, a hepatitis B surface antigen binding protein that was discovered through screening a human liver cDNA expression library, was introduced into hepatitis B vaccine. A good laboratory practice, non-clinical safety evaluation was performed to identify the side effects of both SBP and SBP-adjuvanted hepatitis B vaccine...
2017: PloS One
https://www.readbyqxmd.com/read/28103319/an-hsv-2-trivalent-vaccine-is-immunogenic-in-rhesus-macaques-and-highly-efficacious-in-guinea-pigs
#3
Sita Awasthi, Lauren M Hook, Carolyn E Shaw, Bapi Pahar, Jacob A Stagray, David Liu, Ronald S Veazey, Harvey M Friedman
A genital herpes vaccine is urgently needed to prevent pain and suffering, reduce the incidence of neonatal herpes, and decrease the risk of HIV acquisition and transmission that accompanies genital infection. We evaluated a trivalent HSV-2 subunit antigen vaccine administered with CpG and alum in rhesus macaques and guinea pigs. The vaccine contains glycoproteins C, D and E (gC2, gD2, gE2) to block virus entry by gD2 and immune evasion by gC2 and gE2. In rhesus macaques, the trivalent vaccine induced plasma and mucosa neutralizing antibodies, antibodies that block gC2 and gE2 immune evasion activities, and stimulated CD4 T cell responses...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28103317/genetically-thermo-stabilised-immunogenic-poliovirus-empty-capsids-a-strategy-for-non-replicating-vaccines
#4
Helen Fox, Sarah Knowlson, Philip D Minor, Andrew J Macadam
While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated) vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vaccines as production is thought safer...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28102671/structural-analysis-of-glycosylated-intact-hiv-1-gp120-b12-antibody-complex-using-hydroxyl-radical-protein-footprinting
#5
Xiaoyan Li, Oliver C Grant, Keigo Ito, Aaron Wallace, Shixia Wang, Peng Zhao, Lance Wells, Shan Lu, Robert J Woods, Joshua S Sharp
Glycoprotein gp120 is a surface antigen and virulence factor of the human immunodeficiency virus-1 (HIV-1). Broadly neutralizing antibodies (bNAbs) that are reactive to gp120 from a variety of HIV isolates offer hope for the development of broadly effective immunogens for vaccination purposes, if the interactions between gp120 and bNAbs can be understood. From a structural perspective, gp120 is a particularly difficult system due to its size, the presence of multiple flexible regions, and the large amount of glycosylation, all of which are important in gp120-bNAb interactions...
January 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28100497/avian-derived-and-human-seasonal-derived-hemagglutinin-proteins-elicit-cd4-t-cell-responses-that-are-comparable-in-epitope-abundance-and-diversity
#6
Anthony DiPiazza, Katherine Richards, Nicholas Poulton, Andrea J Sant
Avian influenza viruses remain a significant concern due to their pandemic potential. Vaccine trials have suggested that humans respond poorly to avian influenza vaccines, relative to seasonal vaccines. It is important to understand, first, if there is a general deficiency in the ability of avian HA proteins to generate immune responses and if so, what underlies this defect. This question is of particular interest because it has been suggested that in humans, the poor immunogenicity of H7 vaccines may be due to a paucity of CD4 T cell epitopes...
January 18, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28099485/cell-based-systems-biology-analysis-of-human-as03-adjuvanted-h5n1-avian-influenza-vaccine-responses-a-phase-i-randomized-controlled-trial
#7
Leigh M Howard, Kristen L Hoek, Johannes B Goll, Parimal Samir, Allison Galassie, Tara M Allos, Xinnan Niu, Laura E Gordy, C Buddy Creech, Nripesh Prasad, Travis L Jensen, Heather Hill, Shawn E Levy, Sebastian Joyce, Andrew J Link, Kathryn M Edwards
BACKGROUND: Vaccine development for influenza A/H5N1 is an important public health priority, but H5N1 vaccines are less immunogenic than seasonal influenza vaccines. Adjuvant System 03 (AS03) markedly enhances immune responses to H5N1 vaccine antigens, but the underlying molecular mechanisms are incompletely understood. OBJECTIVE AND METHODS: We compared the safety (primary endpoint), immunogenicity (secondary), gene expression (tertiary) and cytokine responses (exploratory) between AS03-adjuvanted and unadjuvanted inactivated split-virus H5N1 influenza vaccines...
2017: PloS One
https://www.readbyqxmd.com/read/28099431/exacerbated-leishmaniasis-caused-by-a-viral-endosymbiont-can-be-prevented-by-immunization-with-its-viral-capsid
#8
Patrik Castiglioni, Mary-Anne Hartley, Matteo Rossi, Florence Prevel, Chantal Desponds, Daniel T Utzschneider, Remzi-Onur Eren, Haroun Zangger, Livia Brunner, Nicolas Collin, Dietmar Zehn, F Matthew Kuhlmann, Stephen M Beverley, Nicolas Fasel, Catherine Ronet
Recent studies have shown that a cytoplasmic virus called Leishmaniavirus (LRV) is present in some Leishmania species and acts as a potent innate immunogen, aggravating lesional inflammation and development in mice. In humans, the presence of LRV in Leishmania guyanensis and in L. braziliensis was significantly correlated with poor treatment response and symptomatic relapse. So far, no clinical effort has used LRV for prophylactic purposes. In this context, we designed an original vaccine strategy that targeted LRV nested in Leishmania parasites to prevent virus-related complications...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28097690/an-overview-of-structural-features-of-antibacterial-glycoconjugate-vaccines-that-influence-their-immunogenicity
#9
REVIEW
Farjana Khatun, Rachel J Stephenson, Istvan Toth
Bacterial cell-surface-derived or mimicked carbohydrate moieties that act as protective antigens are used in the development of antibacterial glycoconjugate vaccines. The carbohydrate antigen must have a minimum length or size to maintain the conformational structure of the antigenic epitope(s). The presence or absence of O-acetate, phosphate, glycerol phosphate and pyruvate ketal plays a vital role in defining the immunogenicity of the carbohydrate antigen. The nature of the carrier protein, spacer and conjugation pattern used to develop the glycoconjugate vaccine also defines its overall spatial orientation which in turn affects its avidity and selectivity of interaction with the desired target(s)...
November 7, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28097230/protection-against-plasmodium-falciparum-malaria-by-pfspz-vaccine
#10
Judith E Epstein, Kristopher M Paolino, Thomas L Richie, Martha Sedegah, Alexandra Singer, Adam J Ruben, Sumana Chakravarty, April Stafford, Richard C Ruck, Abraham G Eappen, Tao Li, Peter F Billingsley, Anita Manoj, Joana C Silva, Kara Moser, Robin Nielsen, Donna Tosh, Susan Cicatelli, Harini Ganeshan, Jessica Case, Debbie Padilla, Silas Davidson, Lindsey Garver, Elizabeth Saverino, Tooba Murshedkar, Anusha Gunasekera, Patrick S Twomey, Sharina Reyes, James E Moon, Eric R James, Natasha Kc, Minglin Li, Esteban Abot, Arnel Belmonte, Kevin Hauns, Maria Belmonte, Jun Huang, Carlos Vasquez, Shon Remich, Mary Carrington, Yonas Abebe, Amy Tillman, Bradley Hickey, Jason Regules, Eileen Villasante, B Kim Lee Sim, Stephen L Hoffman
BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy against heterologous Pf (different from Pf in the vaccine), after fewer doses, and at 24 weeks. METHODS: The trial assessed tolerability, safety, immunogenicity, and protective efficacy of direct venous inoculation (DVI) of 3 or 5 doses of PfSPZ Vaccine in non-immune subjects...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28096968/a-novel-atheroprotective-role-of-mf59-like-adjuvant-when-co-administered-with-cetp-vaccine-in-rabbit-model-of-atherosclerosis
#11
Tamara Aghebati, Amir Hooshang Mohammadpour, Mohammad Afshar, Mahmoud Reza Jaafari, Khalil Abnous, Saeed Nazemi, Sobhan Issazadeh, Saeed Hashemzadeh, Mohammad Zare, Ali Badiee
OBJECTIVES: In this study, for the first time, MF59 adjuvant was used to develop a cholesteryl ester transfer protein (CETP) vaccine. The efficacy of the vaccine was compared with the efficacy of CETP vaccine formulated with Alum/CpG, the formulation that its immunogenicity has been already demonstrated in rabbit and mice. MATERIALS AND METHODS: Tetanus toxoid- CETP peptide (TT-CETP) was mixed with Alum/CpG or MF59-like and administered subcutaneously for total five times in rabbit model of atherosclerosis...
December 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28096848/immunogenicity-and-efficacy-of-live-l-tarentolae-expressing-kmp11-ntgp96-gfp-fusion-as-a-vaccine-candidate-against-experimental-visceral-leishmaniasis-caused-by-l-infantum
#12
Vahid Nasiri, Abdolhossein Dalimi, Fatemeh Ghaffarifar, Azam Bolhassani
BACKGROUND: The aim of present study was to evaluate the protective efficacy of live recombinant L. tarentolae expressing KMP11-NTGP96-GFP fusion as candidates for live engineered recombinant vaccine against visceral leishmaniasis in BALB/c mice. METHODS: KMP-11 and NT-GP96 genes cloned into the pJET1.2/blunt cloning vector and then into pEGFP-N1 expression vector. The KMP-11, NT-GP96 and GFP fused in pEGFP-N1 and subcloned into Leishmanian pLEXSY-neo vector. Finally this construct was transferred to L...
April 2016: Iranian Journal of Parasitology
https://www.readbyqxmd.com/read/28096331/one-step-design-of-a-stable-variant-of-the-malaria-invasion-protein-rh5-for-use-as-a-vaccine-immunogen
#13
Ivan Campeotto, Adi Goldenzweig, Jack Davey, Lea Barfod, Jennifer M Marshall, Sarah E Silk, Katherine E Wright, Simon J Draper, Matthew K Higgins, Sarel J Fleishman
Many promising vaccine candidates from pathogenic viruses, bacteria, and parasites are unstable and cannot be produced cheaply for clinical use. For instance, Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is essential for erythrocyte invasion, is highly conserved among field isolates, and elicits antibodies that neutralize in vitro and protect in an animal model, making it a leading malaria vaccine candidate. However, functional RH5 is only expressible in eukaryotic systems and exhibits moderate temperature tolerance, limiting its usefulness in hot and low-income countries where malaria prevails...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095712/current-views-on-the-potential-for-development-of-a-hiv-vaccine
#14
Kristen W Cohen, Nicole Frahm
Despite many recent advances in the HIV prevention landscape, an effective vaccine remains the most promising tool to end the HIV-1 pandemic. Areas covered: This review summarizes past HIV vaccine efficacy trials and current vaccine strategies as well as new approaches about to move into first-in-human trials. Expert opinion: Despite many setbacks in early HIV vaccine efficacy trials, the success of RV144 has provided the glimmer of hope necessary to invigorate the vaccine field, and has led to the development of a large number of vaccine strategies aiming at inducing an array of different immune responses...
January 18, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28094775/nanotechnologies-in-delivery-of-mrna-therapeutics-using-nonviral-vector-based-delivery-systems
#15
REVIEW
S Guan, J Rosenecker
Due to its safe and effective protein expression profile, in vitro transcribed messenger RNA (IVT-mRNA) represents a promising candidate in the development of novel therapeutics for genetic diseases, vaccines or gene editing strategies, especially when its inherent shortcomings (e.g. instability and immunogenicity) have been partially addressed via structural modifications. However, numerous unsolved technical difficulties in successful in vivo delivery of IVT-mRNA have greatly hindered the applications of IVT-mRNA in clinical development...
January 17, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28093452/a-time-to-save
#16
Carol J Baker
Group B Streptococcus (GBS), characterized by Lancefield in 1933, was not recognized as a human pathogen until the early 1970s when it emerged and replaced Escherichia coli as the most common cause of sepsis and meningitis among neonates and young infants. This article briefly gives a personnel account of the discovery of clinical syndromes of GBS distinguished by age at onset, vertical mode of transmission for early-onset disease, meningeal tropism for GBS capsular (CPS) type III strains, and protective CPS epitopes...
January 16, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28091576/adjuvant-and-carrier-protein-dependent-t-cell-priming-promotes-a-robust-antibody-response-against-the-plasmodium-falciparum-pfs25-vaccine-candidate
#17
Andrea J Radtke, Charles F Anderson, Nicolas Riteau, Kelly Rausch, Puthupparampil Scaria, Emily R Kelnhofer, Randall F Howard, Alan Sher, Ronald N Germain, Patrick Duffy
Humoral immune responses have the potential to maintain protective antibody levels for years due to the immunoglobulin-secreting activity of long-lived plasma cells (LLPCs). However, many subunit vaccines under development fail to generate robust LLPC responses, and therefore a variety of strategies are being employed to overcome this limitation, including conjugation to carrier proteins and/or formulation with potent adjuvants. Pfs25, an antigen expressed on malaria zygotes and ookinetes, is a leading transmission blocking vaccine (TBV) candidate for Plasmodium falciparum...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089546/expression-of-interleukin-6-by-a-recombinant-rabies-virus-enhances-its-immunogenicity-as-a-potential-vaccine
#18
Jun Luo, Boyue Zhang, Yuting Wu, Qin Tian, Jing Zhao, Ziyu Lyu, Qiong Zhang, Mingzhu Mei, Yongwen Luo, Xiaofeng Guo
Several studies have confirmed that interleukin-6 (IL6) mediates multiple biological effects that enhance immune responses when used as an adjuvant. In the present study, recombinant rabies virus (RABV) expressing canine IL6 (rHEP-CaIL6) was rescued and its pathogenicity and immunogenicity were investigated in mice. We demonstrated that mice received a single intramuscular immunization with rHEP-CaIL6 showed an earlier increase and higher maximum titres of virus-neutralizing antibody (VNA) as well as anti-RABV antibodies compared with mice immunized with the parent strain...
January 12, 2017: Vaccine
https://www.readbyqxmd.com/read/28088862/self-assembling-peptides-epitopes-as-a-novel-platform-for-anti-cancer-vaccination
#19
Mazda Rad-Malekshahi, Marieke F Fransen, Małgorzata Krawczyk, Mercedeh Mansourian, Meriem Bourajjaj, Jian Chen, Ferry Ossendorp, Wim E Hennink, Enrico Mastrobattista, Maryam Amidi
The aim of the present study was to improve the immunogenicity of peptide epitope vaccines using novel nanocarriers based on self-assembling materials. Several studies demonstrated that peptide antigens in nanoparticulate forms induce stronger immune response than their soluble forms. However, several issues such as poor loading and risk of inducing T cell anergy due to premature release of antigenic epitopes have challenged the clinical success of such systems. In the present study, we developed two vaccine delivery systems by appending a self-assembling peptide (Ac-AAVVLLLW-COOH) or a thermosensitive polymer poly(N-isopropylacrylamide (pNIPAm) to the N-terminus of different peptide antigens (OVA250-264, HPV-E743-57) to generate self-assembling peptide epitopes (SAPEs)...
January 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28088476/a-chimeric-protein-of-abrin-and-abrus-precatorius-agglutinin-that-neutralizes-abrin-mediated-lethality-in-mice
#20
Vinita Tiwari, Shradha Bagaria, Anjali A Karande
Abrin, a type II ribosome inactivating protein from the Abrus precatorius plant, is extremely toxic. It has been shown to be 75 times more potent than its infamous sister toxin, ricin and their potential use in bio-warfare is a cause of major concern. Although several vaccine candidates are under clinical trials for ricin, none are available against abrin. The present study proposes a chimeric protein, comprising of 1-123 amino acids taken from the A chain of abrin and 124-175 amino acids from Abrus precatorius agglutinin A chain, as a vaccine candidate against abrin intoxication...
January 11, 2017: Toxicon: Official Journal of the International Society on Toxinology
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