Plant-made vaccines and therapeutics Fausther-Bovendo, Hugues; Kobinger, Gary
Science (American Association for the Advancement of Science),
08/2021, Volume:
373, Issue:
6556
Journal Article
Peer reviewed
Advances in technology and manufacturing could boost the uptake of molecular farming
Therapeutic proteins such as vaccines, antibodies, hormones, and cytokines are generally produced in bacteria or ...eukaryotic systems, including chicken eggs and mammalian or insect cell cultures, with high production yield according to well-defined regulatory guidelines (
1
). The use of plants for the production of therapeutic proteins, called molecular farming, was proposed as an alternative biomanufacturing method in 1986. The first and only plant-derived therapeutic protein for human use was approved in 2012 for the treatment of Gaucher disease. In 2019, a plant-produced influenza virus vaccine completed phase 3 clinical trials, with encouraging results (
2
). More recently, phase 3 trials for an adjuvanted plant-made vaccine (CoVLP) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (NCT04636697) began in March 2021. These successes have revived interest in plant-produced pharmaceuticals for human use, which could include edible drugs.
Ebola continues to rage in West Africa. In the absence of an approved vaccine or treatment, the priority in controlling this epidemic is to promptly identify and isolate infected individuals. To this ...end, a rapid, highly sensitive, and easy-to-use test for Ebola diagnosis is urgently needed. Here, by using Fe3O4 magnetic nanoparticle (MNP) as a nanozyme probe, we developed a MNP-based immunochromatographic strip (Nanozyme-strip), which detects the glycoprotein of Ebola virus (EBOV) as low as 1ng/mL, which is 100-fold more sensitive than the standard strip method. The sensitivity of the Nanozyme-strip for EBOV detection and diagnostic accuracy for New Bunyavirus clinical samples is comparable with ELISA, but is much faster (within 30min) and simpler (without need of specialist facilities). The results demonstrate that the Nanozyme-strip test can rapidly and sensitively detect EBOV, providing a valuable simple screening tool for diagnosis of infection in Ebola-stricken areas.
•We developed a Nanozyme-strip method, which is 100 times more sensitive than the colloidal gold strip.•The first report of introducing Fe3O4 nanozyme into immunochromatographic strip.•The novel method could be used as a valuable tool for diagnosis of Ebola and other infectious disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
3.
Pre-existing immunity against Ad vectors Fausther-Bovendo, Hugues; Kobinger, Gary P
Human vaccines & immunotherapeutics,
10/3/2014, Volume:
10, Issue:
10
Journal Article
Peer reviewed
Open access
Pre-existing immunity against human adenovirus (HAd) serotype 5 derived vector in the human population is widespread, thus hampering its clinical use. Various components of the immune system, ...including neutralizing antibodies (nAbs), Ad specific T cells and type I IFN activated NK cells, contribute to dampening the efficacy of Ad vectors in individuals with pre-existing Ad immunity. In order to circumvent pre-existing immunity to adenovirus, numerous strategies, such as developing alternative Ad serotypes, varying immunization routes and utilizing prime-boost regimens, are under pre-clinical or clinical phases of development. However, these strategies mainly focus on one arm of pre-existing immunity. Selection of alternative serotypes has been largely driven by the absence in the human population of nAbs against them with little attention paid to cross-reactive Ad specific T cells. Conversely, varying the route of immunization appears to mainly rely on avoiding Ad specific tissue-resident T cells. Finally, prime-boost regimens do not actually circumvent pre-existing immunity but instead generate immune responses of sufficient magnitude to confer protection despite pre-existing immunity. Combining the above strategies and thus taking into account all components regulating pre-existing Ad immunity will help further improve the development of Ad vectors for animal and human use.
COVID-19: towards controlling of a pandemic Bedford, Juliet; Enria, Delia; Giesecke, Johan ...
The Lancet (British edition),
03/2020, Volume:
395, Issue:
10229
Journal Article
Peer reviewed
Open access
Most national response strategies include varying levels of contact tracing and self-isolation or quarantine; promotion of public health measures, including handwashing, respiratory etiquette, and ...social distancing; preparation of health systems for a surge of severely ill patients who require isolation, oxygen, and mechanical ventilation; strengthening health facility infection prevention and control, with special attention to nursing home facilities; and postponement or cancellation of large-scale public gatherings. ...all countries should consider a combination of response measures: case and contact finding; containment or other measures that aim to delay the onset of patient surges where feasible; and measures such as public awareness, promotion of personal protective hygiene, preparation of health systems for a surge of severely ill patients, stronger infection prevention and control in health facilities, nursing homes, and long-term care facilities, and postponement or cancellation of large-scale public gatherings. ...countries with no or a few first cases of COVID-19 should consider active surveillance for timely case finding; isolate, test, and trace every contact in containment; practise social distancing; and ready their health-care systems and populations for spread of infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The 2014-2015 outbreak of Ebola virus (EBOV), originating from Guinea, is now responsible for the infection of >20,000 people in 9 countries. Whereas past filovirus outbreaks in sub-Saharan Africa ...have been rapidly brought under control with comparably few cases, this outbreak has been particularly resistant to containment efforts. Both the general population and primary health care workers have been affected by this outbreak, with hundreds of doctors and nurses being infected in the line of duty. In the absence of approved therapeutics, several caregivers have turned to investigational new drugs as well as experimental therapies in an effort to save lives. This review aims to summarize the candidates currently under consideration for postexposure use in infected patients during the largest EBOV outbreak in history.
One year since the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China, several variants of concern (VOC) have appeared around the world, with some variants ...seeming to pose a greater thread to public health due to enhanced transmissibility or infectivity. This study provides a framework for molecular characterization of novel VOC and investigates the effect of mutations on the binding affinity of the receptor-binding domain (RBD) to human angiotensin-converting enzyme 2 (hACE2) using in silico approach. Notable nonsynonymous mutations in RBD of VOC include the E484K and K417N/T that can be seen in South African and Brazilian variants, and N501Y and D614G that can be seen in all VOC. Phylogenetic analyses demonstrated that although the UK-VOC and the BR-VOC fell in the clade GR, they have different mutation signatures, implying an independent evolutionary pathway. The same is true about SA-VOC and COH-VOC felling in clade GH, but different mutation signatures. Combining molecular interaction modeling and the free energy of binding (FEB) calculations for VOC, it can be assumed that the mutation N501Y has the highest binding affinity in RBD for all VOC, followed by E484K (only for BR-VOC), which favors the formation of a stable complex. However, mutations at the residue K417N/T are shown to reduce the binding affinity. Once vaccination has started, there will be selective pressure that would be in favor of the emergence of novel variants capable of escaping the immune system. Therefore, genomic surveillance should be enhanced to find and monitor new emerging SARS-CoV-2 variants before they become a public health concern.
Ebolavirus Evolution: Past and Present de La Vega, Marc-Antoine; Stein, Derek; Kobinger, Gary P
PLOS pathogens,
11/2015, Volume:
11, Issue:
11
Journal Article
Peer reviewed
Open access
The past year has marked the most devastating Ebola outbreak the world has ever witnessed, with over 28,000 cases and over 11,000 deaths. Ebola virus (EBOV) has now been around for almost 50 years. ...In this review, we discuss past and present outbreaks of EBOV and how those variants evolved over time. We explore and discuss selective pressures that drive the evolution of different Ebola variants, and how they may modify the efficacy of therapeutic treatments and vaccines currently being developed. Finally, given the unprecedented size and spread of the outbreak, as well as the extended period of replication in human hosts, specific attention is given to the 2014-2015 West African outbreak variant (Makona).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Seven years after the Middle East respiratory syndrome (MERS) outbreak, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) made its first appearance in a food market in Wuhan, China, ...drawing an entirely new course to our lives. As the virus belongs to the same genus of MERS and SARS, researchers have been trying to draw lessons from previous outbreaks to find a potential cure. Although there were five Phase I human vaccine trials against SARS and MERS, the lack of data in humans provided us with limited benchmarks that could help us design a new vaccine for Coronavirus disease 2019 (COVID-19). In this review, we showcase the similarities in structures of virus components between SARS-CoV, MERS-CoV, and SARS-CoV-2 in areas relevant to vaccine design. Using the ClinicalTrials.gov and World Health Organization (WHO) databases, we shed light on the 16 current approved clinical trials worldwide in search for a COVID-19 vaccine. The different vaccine platforms being tested are Bacillus Calmette-Guérin (BCG) vaccines, DNA and RNA-based vaccines, inactivated vaccines, protein subunits, and viral vectors. By thoroughly analyzing different trials and platforms, we also discuss the advantages and disadvantages of using each type of vaccine and how they can contribute to the design of an adequate vaccine for COVID-19. Studying past efforts invested in conducting vaccine trials for MERS and SARS will provide vital insights regarding the best approach to designing an effective vaccine against COVID-19.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the ...2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use.
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DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Identifying mosquito species is a fundamental step in risk assessment and implementation of preventative strategies. Moreover, Culex pipiens is the most widespread mosquito vector in several regions ...of Iran and is the main vector for transmission of West Nile virus (WNV). Mosquitoes were collected at 14 sites in northern regions of Iran in 2015 and 2016. A subset of mosquito specimens was selected for identification confirmation using a DNA-barcoding technique. Construction of a phylogenetic tree showed clustering of mosquito sequences into three main genera: Aedes, Anopheles and Culex with individuals of a single species clustered closely together, regardless of where and when they were collected. Cx. pipiens complex and Cx. torrentium were identified and differentiated using multiplex real-time PCR targeting the gene locus for acetylcholinesterase 2 (ace2) to discriminate between Cx. pipiens pipiens and Cx. torrentium. The CQ11 microsatellite locus was used for discrimination between Cpp. biotypes. The predominant mosquito species in investigated regions were Cx. pipiens pipiens biotype pipiens, but we also detected Culex pipiens pipiens biotype molestus and hybrids of the two pipiens biotypes, as well as Cx. torrentium. The results of this study represent the first certain evidence of the presence of Cx. pipiens pipiens biotype molestus and hybrids between pipiens and molestus forms, and Cx. torrentium in Iran through a molecular identification approach. This report of a potentially important bridge vector for WNV might have key influence in the risk projections for WNV in Iran.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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