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vaccine adjuvants

Jiansong Zhang, Meifen Wang, Nini Zhou, Yijuan Shen, Yufeng Li
The Gram-negative pathogen toxigenic P. multocida causes progressive atrophic rhinitis (PAR) in swine throughout the world. Although some vaccines are being developed against PAR, their efficacy has not been evaluated using carbopol. In our study, a mixture of killed B. bronchiseptica and P. multocida bacteria, combined with recombinant proteins containing the C- and N-termini of PMT, was emulsified using two different adjuvants (ISA-15A and carbopol 971). The efficacy of these two vaccines was evaluated in a mouse model...
June 13, 2018: Vaccine
Bo Lou, Ans De Beuckelaer, George R Dakwar, Katrien Remaut, Johan Grooten, Kevin Braeckmans, Bruno G De Geest, Enrico Mastrobattista, Stefaan De Koker, Wim E Hennink
Potent adjuvants are highly demanded for most protein and peptides based vaccine candidates in clinical development. Recognition of viral single stranded (ss)RNA by innate toll-like receptors 7/8 in dendritic cells results in a cytokine environment supportive to the establishment of long lasting antibody responses and Th1 oriented T cell immunity. To fully exploit the immunestimulatory properties of ssRNA, it needs to be adequately formulated to ensure its optimal delivery to dendritic cells in the vaccine draining lymph nodes...
June 14, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Mona Mohammadzadeh, Babak Pourakbari, Shima Mahmoudi, Abbas Keshtkar, Mahdi Habibi-Anbouhi, Setareh Mamishi
BACKGROUND: Despite the fact that pneumococcal conjugate vaccines (PCVs) have significantly reduced the rate of invasive pneumococcal diseases through the use of vaccine serotypes, infection with Streptococcus pneumoniae remains a major public health hazard. Serotype-independent vaccines that are economically viable species of common protein antigens such as whole-cell vaccines (WCVs) are needed. Considering the ongoing debate about the effectiveness of WCVs, a systematic literature review and meta-analysis was carried out to determine the efficacy of WCVs against colonization in mice...
June 13, 2018: Microbial Pathogenesis
Jordana Grazziela Coelho-Dos-Reis, Xiangming Li, Moriya Tsuji
The inability to elicit strong and durable cellular responses is a major obstacle in the development of successful vaccines, in particular those against malaria. In this regard, the generation of novel adjuvants that will potently boost cell-mediated immunity induced by candidate vaccines is helpful. We and others have found a glycolipid, called α-galactosylceramide (α-GalCer), which could be presented on CD1d expressed by antigen-presenting cells (APCs) and stimulate natural killer T (NKT) cells. This triggers the activation/maturation of APCs, particularly dendritic cells (DCs)...
2018: F1000Research
Céline Maréchal, Himal Lal, Airi Poder, Murdo Ferguson, Igwebuike Enweonye, Thomas C Heineman, Caroline Hervé, Paul Rheault, Jaak Talli, Dominique Wauters, Lidia Oostvogels
BACKGROUND: This study evaluated immunogenicity and safety of the adjuvanted recombinant zoster vaccine (RZV) when the first dose was co-administered with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in adults aged ≥50 years. METHODS: In this open label, multi-center study (NCT02045836), participants were randomized 1:1 to receive either the first dose of RZV and PPSV23, co-administered at Day 0 and the second dose of RZV at Month 2 (Co-Ad group), or PPSV23 at Day 0, the first dose of RZV at Month 2 and second dose of RZV at Month 4 (Control group)...
June 11, 2018: Vaccine
Daiki Nomura, Masaaki Saito, Yosuke Takahashi, Yuki Takahashi, Yoshinobu Takakura, Makiya Nishikawa
Self-gelling DNA hydrogels with cytosine-phosphate-guanine (CpG) motifs have been shown to exhibit high potency as vaccine adjuvants. However, their oral use is limited because of their thermodynamic and chemical instability in the gastrointestinal tract. In this study, we aimed to develop DNA hydrogel microspheres (Dgel-MS) coated with chitosan to improve their stability. Chitosan-coated Dgel-MS (Cs-Dgel-MS) was prepared by emulsifying Dgel to obtain the D-gel core, followed by mixing with microemulsions of chitosan for electrostatic coating...
June 11, 2018: International Journal of Pharmaceutics
Rajan Kumar Pandey, Rupal Ojha, Amit Mishra, Vijay Kumar Prajapati
The Zika virus is a rapidly spreading Aedes mosquito-borne sickness, which creates an unanticipated linkage birth deformity and neurological turmoil. This study represents the use of the combinatorial immunoinformatics approach to develop a multiepitope subunit vaccine using the structural and nonstructural proteins of the Zika virus. The designed subunit vaccine consists of cytotoxic T-lymphocyte and helper T-lymphocyte epitopes accompanied by suitable adjuvant and linkers. The presence of humoral immune response specific B-cell epitopes was also confirmed by B-cell epitope mapping among vaccine protein...
June 14, 2018: Journal of Cellular Biochemistry
Mayuresh M Abhyankar, Mark T Orr, Susan Lin, Mohammed O Suraju, Adrian Simpson, Molly Blust, Tiep Pham, Jeffrey A Guderian, Mark A Tomai, James Elvecrog, Karl Pedersen, William A Petri, Christopher B Fox
Amebiasis caused by Entamoeba histolytic a is the third leading cause of parasitic mortality globally, with some 100,000 deaths annually, primarily among young children. Protective immunity to amebiasis is associated with fecal IgA and IFN-γ in humans; however, no vaccine exists. We have previously identified recombinant LecA as a potential protective vaccine antigen. Here we describe the development of a stable, manufacturable PEGylated liposomal adjuvant formulation containing two synthetic Toll-like receptor (TLR) ligands: GLA (TLR4) and 3M-052 (TLR7/8)...
2018: NPJ Vaccines
Eita Sasaki, Haruka Momose, Yuki Hiradate, Keiko Furuhata, Takuo Mizukami, Isao Hamaguchi
Safety evaluation of a human vaccine is critical for vaccine development and for preventing an unexpected adverse reaction in humans. Nonetheless, to date, very few systems have been described for preclinical studies of human adverse reactions in vivo . Previously, we have identified biomarker genes expressed in the lungs for evaluation of influenza vaccine safety, and their usefulness in rodent models and for adjuvant-containing vaccines has already been reported. Here, our purpose was to develop a novel humanized mouse model retaining human innate-immunity-related cells to assess the safety of influenza vaccines using the previously identified biomarker genes...
May 25, 2018: Oncotarget
Vandana Solanki, Vishvanath Tiwari
The emergence of drug-resistant Acinetobacter baumannii is the global health problem associated with high mortality and morbidity. Therefore it is high time to find a suitable therapeutics for this pathogen. In the present study, subtractive proteomics along with reverse vaccinology approaches were used to predict suitable therapeutics against A. baumannii. Using subtractive proteomics, we have identified promiscuous antigenic membrane proteins that contain the virulence factors, resistance factors and essentiality factor for this pathogenic bacteria...
June 13, 2018: Scientific Reports
Arif A Khan, Ruchi Srivastava, Hawa Vahed, Soumyabrata Roy, Sager S Walia, Grace J Kim, Mona A Fouladi, Taikun Yamada, Vincent T Ly, Cynthia Lam, Anthony Lou, Vivianna Nguyen, Undariya Boldbaatar, Roger Geertsema, Nigel W Fraser, Lbachir BenMohamed
Herpes simplex virus 1 (HSV-1) is a prevalent human pathogen that infects the cornea causing potentially blinding herpetic disease. A clinical herpes vaccine is still lacking. In the present study, a novel prime/pull vaccine was tested in Human Leukocyte Antigen- (HLA-) transgenic rabbit model of ocular herpes (HLA Tg rabbit). Three asymptomatic (ASYMP) peptide epitopes were selected from the HSV-1 membrane glycoprotein C (UL44400-408 ), the DNA replication binding helicase (UL9196-204 ), and the tegument protein (UL25572-580 ), all preferentially recognized by CD8+ T cells from "naturally protected" HSV-1-seropositive healthy ASYMP individuals (who never had recurrent corneal herpetic disease)...
June 13, 2018: Journal of Virology
Linda-Gail Bekker, Zoe Moodie, Nicole Grunenberg, Fatima Laher, Georgia D Tomaras, Kristen W Cohen, Mary Allen, Mookho Malahleha, Kathryn Mngadi, Brodie Daniels, Craig Innes, Carter Bentley, Nicole Frahm, Daryl E Morris, Lynn Morris, Nonhlanhla N Mkhize, David C Montefiori, Marcella Sarzotti-Kelsoe, Shannon Grant, Chenchen Yu, Vijay L Mehra, Michael N Pensiero, Sanjay Phogat, Carlos A DiazGranados, Susan W Barnett, Niranjan Kanesa-Thasan, Marguerite Koutsoukos, Nelson L Michael, Merlin L Robb, James G Kublin, Peter B Gilbert, Lawrence Corey, Glenda E Gray, M Juliana McElrath
BACKGROUND: Modest efficacy was reported for the HIV vaccine tested in the RV144 trial, which comprised a canarypox vector (ALVAC) and envelope (env) glycoprotein (gp120). These vaccine components were adapted to express HIV-1 antigens from strains circulating in South Africa, and the adjuvant was changed to increase immunogenicity. Furthermore, 12-month immunisation was added to improve durability. In the HIV Vaccine Trials Network (HVTN) 100 trial, we aimed to assess this new regionally adapted regimen for advancement to efficacy testing...
June 8, 2018: Lancet HIV
João F Gomes-Neto, Rossella Sartorius, Fábio B Canto, Thamyres S Almeida, André A Dias, Carlos-Henrique D Barbosa, Guilherme A Melo, Ana Carolina Oliveira, Pedro-Henrique N Aguiar, Carlos R Machado, Herbert L de Matos Guedes, Marcelo F Santiago, Alberto Nóbrega, Piergiuseppe De Berardinis, Maria Bellio
Recombinant filamentous fd bacteriophages (r fd ) expressing antigenic peptides were shown to induce cell-mediated immune responses in the absence of added adjuvant, being a promising delivery system for vaccination. Here, we tested the capacity of r fd phages to protect against infection with the human protozoan Trypanosoma cruzi , the etiologic agent of Chagas Disease. For this, C57BL/6 (B6) and Tlr9- / - mice were vaccinated with r fd phages expressing the OVA257-264 peptide or the T. cruzi -immunodominant peptides PA8 and TSKB20 and challenged with either the T...
2018: Frontiers in Immunology
N Dobrovolskienė, V Pašukonienė, A Darinskas, J A Kraśko, K Žilionytė, A Mlynska, Ž Gudlevičienė, E Mišeikytė-Kaubrienė, V Schijns, W Lubitz, P Kudela, M Strioga
Cancer immunotherapy with dendritic cell (DC)-based vaccines has been used to treat various malignancies for more than two decades, however generally showed a limited clinical success. Among various factors responsible for their modest clinical activity is the lack of universally applied, standardized protocols for the generation of clinical-grade DC vaccines, capable of inducing effective anti-tumor immune responses. We investigated Bacterial Ghosts (BGs) - empty envelopes of Gram-negative bacteria - as a tool for optimized production of DC vaccines...
June 9, 2018: Vaccine
Christina Joyce, Ciaran D Scallan, Roberto Mateo, Robert B Belshe, Sean N Tucker, Anne C Moore
A vaccine against Respiratory Syncytial Virus (RSV) is a major unmet need to prevent the significant morbidity and mortality that it causes in society. In addition to efficacy, such a vaccine must not induce adverse events, as previously occurred with a formalin-inactivated vaccine (FI-RSV). In this study, the safety, immunogenicity and efficacy of a molecularly adjuvanted adenovirus serotype 5 based RSV vaccine encoding the fusion (F) protein (Ad-RSVF) is demonstrated in cotton rats. Protective immunity to RSV was induced by Ad-RSVF when administered by an oral route as well as by intranasal and intramuscular routes...
June 9, 2018: Vaccine
Zhuang-Zhi Zhang, Gang Guo, Jun Li, Bao-Xin Shi, Li Zhao, Bao-Ping Guo, Xu Zhang, Jun-Wei Wang, Xue-Ting Zheng, Wen-Jing Qi, Li He, Wen-Bao Zhang
BACKGROUND: Dogs play a pivotal role in the transmission of cystic echinococcosis (CE), a zoonosis caused by the tapeworm Echinococcus granulosus. We showed previously that dogs vaccinated with two E. granulosus adult-worm specific proteins, EgM9 and EgM123, emulsified with Freund's adjuvants induced significant protective efficacy in terms of reduction in worm burden and egg production after 45 days post-infection. It was not known whether this protection can be sustained using adjuvants suitable for use in dogs...
June 13, 2018: Infectious Diseases of Poverty
Alexander Batista-Duharte, Damiana Téllez Martínez, Iracilda Zeppone Carlos
Research over the past several decades has provided insight into the mode of action of adjuvants. However, the main focus of attention has been the efficacy in the induction of protective immunogenicity, while less effort has been devoted to the study of toxicity mechanisms. Evidences suggest that several mechanisms that are responsible for the immunostimulating effects are, at the same time, responsible of the adverse effects. In this context, it is often very difficult to establish the boundaries between immunostimulation and immunotoxicity to reach the ideal balance of efficacy/safety...
June 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ya-Hsuan Chao, Der-Yuan Chen, Joung-Liang Lan, Kuo-Tung Tang, Chi-Chien Lin
DNA vaccines have recently emerged as a therapeutic agent for treating autoimmune diseases, such as multiple sclerosis. Antiphospholipid antibody syndrome (APS) is an autoimmune disease characterized by β2-glycoprotein I (β2-GPI)-targeting antiphospholipid antibodies (APAs) and vascular thrombosis or obstetrical complications. To examine the therapeutic potential of a β2-GPI DNA vaccine, we administered a vaccine mixed with FK506 as an adjuvant to a mouse model of obstetric APS. First, the pCMV3-β2-GPI DNA vaccine, which encodes the full-length human β2-GPI gene, was constructed...
2018: PloS One
Ying Liu, Ling Ye, Fang Lin, Yasmine Gomaa, David Flyer, Ricardo Carrion, Jean L Patterson, Mark R Prausnitz, Gale Smith, Gregory Glenn, Hua Wu, Richard W Compans, Chinglai Yang
In this study, we investigated immune responses induced by purified Ebola virus (EBOV) soluble glycoprotein (sGP) subunit vaccines via intradermal immunization with microneedle (MN) patches in comparison with intramuscular (IM) injection in mice. Our results showed that MN delivery of EBOV sGP was superior to IM injection in eliciting higher levels and longer lasting antibody responses against EBOV sGP and GP antigens. Moreover, sGP-specific immune responses induced by MN or IM immunizations were effectively augmented by formulating sGP with a saponin-based adjuvant, and they were shown to confer complete protection of mice against lethal mouse-adapted EBOV (MA-EBOV) challenge...
June 8, 2018: Journal of Infectious Diseases
Mangala Rao, Sayali Onkar, Kristina K Peachman, Yohann White, Hung V Trinh, Ousman Jobe, Yingjun Zhou, Peter Dawson, Michael A Eller, Gary R Matyas, Carl R Alving
Background: In the RV144 trial, HIV-1 gp120 V1V2 antibodies correlated inversely with risk of HIV-1 infection; however the titers waned quickly. We hypothesized that a more potent adjuvant might enhance the magnitude and durability of V1V2 antibodies. Methods: We examined archived sera from a phase I randomized, double blind placebo-controlled trial, conducted in HIV-1 uninfected individuals, vaccinated with HIV-1SF-2 rgp120 either adsorbed to aluminum hydroxide (aluminum hydroxide arm) or encapsulated in liposomes containing monophosphoryl lipid A (MPL®) and then adsorbed to aluminum hydroxide (liposomal arm)...
June 9, 2018: Journal of Infectious Diseases
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