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Ebola vaccine

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https://www.readbyqxmd.com/read/28795602/immunogenicity-of-the-recombinant-adenovirus-type-5-vector-based-ebola-vaccine-ad5-ebov-expressing-the-glycoprotein-of-the-2014-epidemic-strain-in-mice
#1
Ling Wang, Jing Jing Liu, Yan Kong, Li Hua Hou, Yu Hua Li
The 2014 Ebola outbreak in West Africa has brought great threat to the public health worldwide. Development of Ebola vaccine is urgent. A novel recombinant adenovirus type-5 vector-based Ebola vaccine (Ad5-EBOV) based on the 2014 Zaire Guinea epidemic strain was developed in China. A good safety profile and robust immune response elicited by Ad5-EBOV were confirmed in Phase I and Phase II clinical trial. However, clinical studies of Ebola vaccine are still at an early stage and no solid efficacy data for human beings yet...
August 10, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28791241/ebola-virus-disease-essential-clinical-knowledge
#2
REVIEW
Mahmoud Tawfik Khalafallah, Omar Ali Aboshady, Shaban Ahmed Moawed, Menna Said Ramadan
Since its initial outbreak in 1976, Ebola virus disease (EVD) has affected thousands of people, causing severe illness with high mortality rates. In the absence of a vaccine or effective specific treatment, as well as the lack of early diagnostic and detective methods, the EVD outbreak has generated a significant worldwide health concern. Insufficient health-care system resources, deficient infection control measures, and the shortage of appropriate personal protective equipment acted as amplifiers of the outbreak extension, especially in poorly resourced and unprepared communities...
July 2017: Avicenna Journal of Medicine
https://www.readbyqxmd.com/read/28780120/vaccines-against-ebola-virus
#3
Navin Venkatraman, Daniel Silman, Pedro M Folegatti, Adrian V S Hill
We have just witnessed the largest and most devastating outbreak of Ebola virus disease, which highlighted the urgent need for development of an efficacious vaccine that could be used to curtail future outbreaks. Prior to 2014, there had been limited impetus worldwide to develop a vaccine since the virus was first discovered in 1976. Though too many lives were lost during this outbreak, it resulted in the significantly accelerated clinical development of a number of candidate vaccines through an extraordinary collaborative global effort coordinated by the World Health Organisation (WHO) and involving a number of companies, trial centres, funders, global stakeholders and agencies...
August 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28768877/immunodominance-of-adenovirus-derived-cd8-t-cell-epitopes-interferes-with-the-induction-of-transgene-specific-immunity-in-adenovirus-based-immunization
#4
Dominik Schöne, Camilla Patrizia Hrycak, Sonja Windmann, Dennis Lapuente, Ulf Dittmer, Matthias Tenbusch, Wibke Bayer
Adenovirus (Ad)-based immunization is a popular approach in vaccine development, and Ad-based vectors are renowned for their potential to induce strong CD8(+) T cell responses to the encoded transgene. Surprisingly, we found before in the mouse Friend retrovirus (FV) model that Ad-based immunization did not induce CD8(+) T cell responses to the FV Leader-Gag-derived immunodominant epitope GagL85-93 We show now that induction of GagL85-93-specific CD8(+) T cells was highly effective when Leader-Gag was delivered by plasmid DNA immunization, implying a role for Ad-derived epitopes in mediating unresponsiveness...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768865/ubiquitin-ligase-wwp1-interacts-with-ebola-virus-vp40-to-regulate-egress
#5
Ziying Han, Cari A Sagum, Fumio Takizawa, Gordon Ruthel, Corbett T Berry, Jing Kong, J Oriol Sunyer, Bruce D Freedman, Mark T Bedford, Sachdev S Sidhu, Marius Sudol, Ronald N Harty
Ebola virus (EBOV) is a member of the Filoviridae family and the cause of hemorrhagic fever outbreaks. The EBOV VP40 (eVP40) matrix protein is the main driving force for virion assembly and budding. Indeed, expression of eVP40 alone in mammalian cells results in the formation and budding of virus-like particles (VLPs), which mimics the budding process and morphology of authentic, infectious EBOV. To complete the budding process, eVP40 utilizes its PPxY L-domain motif to recruit a specific subset of host proteins containing one or more modular WW-domains that then function to facilitate efficient production and release of eVP40 VLPs...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28743299/the-public-health-value-of-vaccines-beyond-efficacy-methods-measures-and-outcomes
#6
A Wilder-Smith, I Longini, P L Zuber, T Bärnighausen, W J Edmunds, N Dean, V Masserey Spicher, M R Benissa, B D Gessner
BACKGROUND: Assessments of vaccine efficacy and safety capture only the minimum information needed for regulatory approval, rather than the full public health value of vaccines. Vaccine efficacy provides a measure of proportionate disease reduction, is usually limited to etiologically confirmed disease, and focuses on the direct protection of the vaccinated individual. Herein, we propose a broader scope of methods, measures and outcomes to evaluate the effectiveness and public health impact to be considered for evidence-informed policymaking in both pre- and post-licensure stages...
July 26, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28733113/a-heterologous-prime-boost-ebola-virus-vaccine-regimen-induces-durable-neutralizing-antibody-response-and-prevents-ebola-virus-like-particle-entry-in-mice
#7
Tan Chen, Dapeng Li, Yufeng Song, Xi Yang, Qingwei Liu, Xia Jin, Dongming Zhou, Zhong Huang
Ebola virus (EBOV) is one of the most virulent pathogens known to humans. Neutralizing antibodies play a major role in the protection against EBOV infections. Thus, an EBOV vaccine capable of inducing a long-lasting neutralizing antibody response is highly desirable. We report here that a heterologous prime-boost vaccine regimen can elicit durable EBOV-neutralizing antibody response in mice. A chimpanzee serotype 7 adenovirus expressing EBOV GP (denoted AdC7-GP) was generated and used for priming. A truncated version of EBOV GP1 protein (denoted GP1t) was produced at high levels in Drosophila S2 cells and used for boosting...
July 18, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28729706/sudan-ebolavirus-long-recovered-survivors-produce-gp-specific-abs-that-are-of-the-igg1-subclass-and-preferentially-bind-fc%C3%AE-ri
#8
Olga Radinsky, Avishay Edri, Michael Brusilovsky, Shlomit Fedida-Metula, Ariel Sobarzo, Orly Gershoni-Yahalom, Julius Lutwama, John Dye, Leslie Lobel, Angel Porgador
Ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724616/marburg-virus-survivor-immune-responses-are-th1-skewed-with-limited-neutralizing-antibody-responses
#9
Spencer W Stonier, Andrew S Herbert, Ana I Kuehne, Ariel Sobarzo, Polina Habibulin, Chen V Abramovitch Dahan, Rebekah M James, Moses Egesa, Stephen Cose, Julius Julian Lutwama, Leslie Lobel, John M Dye
Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized...
July 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28721831/transient-production-of-recombinant-pharmaceutical-proteins-in-plants-evolution-and-perspectives
#10
Lilya Kopertekh, Joachim Schiemann
During the last two decades the production of pharmaceutical proteins in plants evolved from proof of concept to established technology adopted by several biotechnological companies. This progress is particularly based on intensive research starting stable genetic transformation and moving to transient expression. Due to its advantages in yield and speed of protein production transient expression platforms became leading plant-based manufacturing technology. Current transient expression methods rely on Agrobacterium-mediated delivery of expression vectors into plant cells...
July 18, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28719299/conventional-wisdom-versus-actual-outcomes-challenges-in-the-conduct-of-an-ebola-vaccine-trial-in-liberia-during-the-international-public-health-emergency
#11
Gregg S Larson, Beth R Baseler, Marie L Hoover, Jerome F Pierson, Jemee K Tegli, Melvin P Johnson, Mark W S Kieh, Laura A McNay, Wissedi Sio Njoh
Clinical trials are challenging endeavors. Planning and implementing an investigational vaccine trial in Liberia, in the midst of an Ebola virus disease (EVD) epidemic that World Health Organization classified a public health emergency of international concern, presented extraordinary challenges. Normally, years of preparation and a litany of tasks lay the groundwork for a successful, randomized, blinded, placebo-controlled trial focused on safety and efficacy. Difficult research settings, unpredictable events, and other unique circumstances can add complexity...
July 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28716555/attitudes-about-vaccines-to-prevent-ebola-virus-disease-in-guinea-at-the-end-of-a-large-ebola-epidemic-results-of-a-national-household-survey
#12
Kathleen L Irwin, Mohamed F Jalloh, Jamaica Corker, Barry Alpha Mahmoud, Susan J Robinson, Wenshu Li, Nyuma E James, Musa Sellu, Mohammad B Jalloh, Alpha Ahmadou Diallo, LaRee Tracy, Rana Hajjeh, Amanda VanSteelandt, Rebecca Bunnell, Lise Martel, Pratima L Raghunathan, Barbara Marston
INTRODUCTION: In 2014-2016, an Ebola epidemic devastated Guinea; more than 3800 cases and 2500 deaths were reported to the World Health Organization. In August 2015, as the epidemic waned and clinical trials of an experimental, Ebola vaccine continued in Guinea and neighboring Sierra Leone, we conducted a national household survey about Ebola-related knowledge, attitudes, and practices (KAP) and opinions about "hypothetical" Ebola vaccines. METHODS: Using cluster-randomized sampling, we selected participants aged 15+ years old in Guinea's 8 administrative regions, which had varied cumulative case counts...
July 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28708962/open-label-phase-i-clinical-trial-of-ad5-ebov-in-africans-in-china
#13
Lihua Wu, Zhe Zhang, Hainv Gao, Yuhua Li, Lihua Hou, Hangping Yao, Shipo Wu, Jian Liu, Ling Wang, You Zhai, Huilin Ou, Meihua Lin, Xiaoxin Wu, Jingjing Liu, Guanjing Lang, Qian Xin, Guolan Wu, Li Luo, Pei Liu, Jianzhong Shentu, Nanping Wu, Jifang Sheng, Yunqing Qiu, Wei Chen, Lanjuan Li
BACKGROUND: To determine the safety and immunogenicity of a novel recombinant adenovirus type 5 vector based Ebola virus disease vaccine (Ad5-EBOV) in Africans in China. METHODS: A phase 1, dose-escalation, open-label trial was conducted. 61 healthy Africans were sequentially enrolled, with 31 participants receiving one shot intramuscular injection and 30 participants receiving a double-shot regimen. Primary and secondary end points related to safety and immunogenicity were assessed within 28 d after vaccination...
July 14, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28706039/when-an-emerging-disease-becomes-endemic
#14
REVIEW
Graham F Medley, Anna Vassall
Epidemics, such as HIV in the early 1980s and Ebola in 2014, inspire decisive government investment and action, and individual and societal concern, sometimes bordering on panic. By contrast, endemic diseases, such as HIV in 2017 and tuberculosis, struggle to maintain the same attention. For many, the paradox is that endemic disease, in its totality, continues to impose a far higher public health burden than epidemic disease. Overall, the swift political response to epidemics has resulted in success. It has proven possible to eradicate epidemic diseases, often without the availability of vaccines and other biomedical technologies...
July 14, 2017: Science
https://www.readbyqxmd.com/read/28699812/epitope-mapping-of-ebola-virus-dominant-and-subdominant-glycoprotein-epitopes-facilitates-construction-of-an-epitope-based-dna-vaccine-able-to-focus-the-antibody-response-in-mice
#15
Daniel A J Mitchell, Lesley C Dupuy, Mariano Sanchez-Lockhart, Gustavo Palacios, Jaap W Back, Katya Shimanovskaya, Sidhartha Chaudhury, Daniel R Ripoll, Anders Wallqvist, Connie S Schmaljohn
We performed epitope mapping studies on the major surface glycoprotein (GP) of Ebola virus (EBOV) using Chemically Linked Peptides on Scaffolds (CLIPS), which form linear and potential conformational epitopes. This method identified monoclonal antibody epitopes and predicted additional epitopes recognized by antibodies in polyclonal sera from animals experimentally vaccinated against or infected with EBOV. Using the information obtained along with structural modeling to predict epitope accessibility, we then constructed two DNA vaccines encoding immunodominant and subdominant epitopes predicted to be accessible on EBOV GP...
July 12, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28679761/the-host-e3-ubiquitin-ligase-trim6-ubiquitinates-the-ebola-virus-vp35-protein-and-promotes-virus-replication
#16
Preeti Bharaj, Colm Atkins, Priya Luthra, Maria Isabel Giraldo, Brian E Dawes, Lisa Miorin, Jeffrey R Johnson, Nevan J Krogan, Christopher F Basler, Alexander N Freiberg, Ricardo Rajsbaum
Ebola virus (EBOV), a member of the Filoviridae family, is a highly pathogenic virus that causes severe hemorrhagic fever in humans and is responsible for epidemics throughout sub-Saharan, central and West Africa. The EBOV genome encodes for VP35, an important viral protein involved in virus replication by acting as an essential cofactor of the viral polymerase as well as a potent antagonist of the host antiviral type-I interferon (IFN-I) system. By using mass spectrometry analysis and co-immunoprecipitation assays, we show here that VP35 is ubiquitinated on lysine 309 (K309), a residue located on its IFN antagonist domain...
July 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28675995/ebola-epidemics-control-origin-and-therapeutics
#17
Da Yong Lu, Hong Ying Wu, Nagendra Sastry Yarla, Ting-Ren Lu, Bin Xu, Jian -Ding
Ebola epidemic in Africa was outbreak again in 2014 that arises a new wave of panic worldwide. There is a high mortality rates (30-70%) among Ebola infected people in virus-stricken areas. The direct communications between affected countries and rest of world were cut off then. But the medical capabilities against this deadly viral disease were provided by a limited number of agents, several patented agents, biotherapies or prophylactic/therapeutic vaccines have been entering into clinical validations and will be further developed into the global markets-including patents of small molecular chemicals, short sequences or oligomers of DNA/RNA, linkages of chemicals with bio-molecules, herbal medicine and so on...
July 3, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28669593/pathogen-mimicking-vaccine-delivery-system-designed-with-a-bioactive-polymer-inulin-acetate-for-robust-humoral-and-cellular-immune-responses
#18
Sunny Kumar, Siddharth S Kesharwani, Bhimanna Kuppast, Mohammed Ali Bakkari, Hemachand Tummala
New and improved vaccines are needed against challenging diseases such as malaria, tuberculosis, Ebola, influenza, AIDS, and cancer. The majority of existing vaccine adjuvants lack the ability to significantly stimulate the cellular immune response, which is required to prevent the aforementioned diseases. This study designed a novel particulate based pathogen-mimicking vaccine delivery system (PMVDS) to target antigen-presenting-cells (APCs) such as dendritic cells. The uniqueness of PMVDS is that the polymer used to prepare the delivery system, Inulin Acetate (InAc), activates the innate immune system...
September 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28663940/considerations-for-use-of-investigational-drugs-in-public-health-emergencies
#19
Matthew Carl Kirchoff, Jerome F Pierson
The paradigm for the use of investigational drugs in public health emergencies has been recently tested to prevent and treat highly infectious and lethal diseases. Examples include the successful implementation of vaccine and therapeutic clinical trials during the recent Ebola outbreak in West Africa. On the other end of the spectrum was the Emergency Use Authorization (EUA) of peramivir in the treatment of H1N1 influenza virus that did not provide an opportunity to collect data or understand the effectiveness of the EUA program...
March 2017: Therapeutic Innovation & Regulatory Science
https://www.readbyqxmd.com/read/28662754/animal-models-of-ebolavirus-infection
#20
Marisa C St Claire, Dan R Ragland, Laura Bollinger, Peter B Jahrling
Ebola virus is a highly pathogenic member of the family Filoviridae that causes a severe hemorrhagic disease in humans and NHP. The 2013-2016 West African outbreak has increased interest in the development and refinement of animal models of Ebola virus disease. These models are used to test countermeasures and vaccines, gain scientific insights into the mechanisms of disease progression and transmission, and study key correlates of immunology. Ebola virus is classified as a BSL4 pathogen and Category A agent, for which the United States government requires preparedness in case of bioterrorism...
June 1, 2017: Comparative Medicine
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