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      New Vaccine Technologies to Combat Outbreak Situations

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          Abstract

          Ever since the development of the first vaccine more than 200 years ago, vaccinations have greatly decreased the burden of infectious diseases worldwide, famously leading to the eradication of small pox and allowing the restriction of diseases such as polio, tetanus, diphtheria, and measles. A multitude of research efforts focuses on the improvement of established and the discovery of new vaccines such as the HPV (human papilloma virus) vaccine in 2006. However, radical changes in the density, age distribution and traveling habits of the population worldwide as well as the changing climate favor the emergence of old and new pathogens that bear the risk of becoming pandemic threats. In recent years, the rapid spread of severe infections such as HIV, SARS, Ebola, and Zika have highlighted the dire need for global preparedness for pandemics, which necessitates the extremely rapid development and comprehensive distribution of vaccines against potentially previously unknown pathogens. What is more, the emergence of antibiotic resistant bacteria calls for new approaches to prevent infections. Given these changes, established methods for the identification of new vaccine candidates are no longer sufficient to ensure global protection. Hence, new vaccine technologies able to achieve rapid development as well as large scale production are of pivotal importance. This review will discuss viral vector and nucleic acid-based vaccines (DNA and mRNA vaccines) as new approaches that might be able to tackle these challenges to global health.

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          Most cited references104

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          Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome

          The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. The novel coronavirus might have a role in causing SARS. Copyright 2003 Massachusetts Medical Society
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            mRNA vaccine delivery using lipid nanoparticles.

            mRNA vaccines elicit a potent immune response including antibodies and cytotoxic T cells. mRNA vaccines are currently evaluated in clinical trials for cancer immunotherapy applications, but also have great potential as prophylactic vaccines. Efficient delivery of mRNA vaccines will be key for their success and translation to the clinic. Among potential nonviral vectors, lipid nanoparticles are particularly promising. Indeed, lipid nanoparticles can be synthesized with relative ease in a scalable manner, protect the mRNA against degradation, facilitate endosomal escape, can be targeted to the desired cell type by surface decoration with ligands, and as needed, can be codelivered with adjuvants.
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              Sequence-engineered mRNA Without Chemical Nucleoside Modifications Enables an Effective Protein Therapy in Large Animals

              Being a transient carrier of genetic information, mRNA could be a versatile, flexible, and safe means for protein therapies. While recent findings highlight the enormous therapeutic potential of mRNA, evidence that mRNA-based protein therapies are feasible beyond small animals such as mice is still lacking. Previous studies imply that mRNA therapeutics require chemical nucleoside modifications to obtain sufficient protein expression and avoid activation of the innate immune system. Here we show that chemically unmodified mRNA can achieve those goals as well by applying sequence-engineered molecules. Using erythropoietin (EPO) driven production of red blood cells as the biological model, engineered Epo mRNA elicited meaningful physiological responses from mice to nonhuman primates. Even in pigs of about 20 kg in weight, a single adequate dose of engineered mRNA encapsulated in lipid nanoparticles (LNPs) induced high systemic Epo levels and strong physiological effects. Our results demonstrate that sequence-engineered mRNA has the potential to revolutionize human protein therapies.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                19 September 2018
                2018
                : 9
                : 1963
                Affiliations
                CureVac AG , Tuebingen, Germany
                Author notes

                Edited by: Aldo Tagliabue, Istituto di Ricerca Genetica e Biomedica (IRGB), Italy

                Reviewed by: Konrad Stadler, Boehringer Ingelheim, Germany; Antonella Folgori, ReiThera Srl, Italy

                *Correspondence: Susanne Rauch susanne.rauch@ 123456curevac.com

                This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2018.01963
                6156540
                30283434
                b88f8e8c-14e0-4676-ab52-debc8fd8d79c
                Copyright © 2018 Rauch, Jasny, Schmidt and Petsch.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 18 May 2018
                : 09 August 2018
                Page count
                Figures: 1, Tables: 4, Equations: 0, References: 181, Pages: 24, Words: 21291
                Categories
                Immunology
                Review

                Immunology
                viral vector vaccine,dna vaccine,mrna vaccine,pandemics,vaccine development
                Immunology
                viral vector vaccine, dna vaccine, mrna vaccine, pandemics, vaccine development

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