Eksploracja metadanych publikacji dotyczących szczepionek mRNA
zamaro@outlook.com
Analiza przeprowadzona na podstawie danych bibliometrycznych biblioteki PubMed. Dane dotycza publikacji zawierajacych w tytulach i abstraktach zwrot "vaccine*“,”mRNA" oraz deskryptor “human[HT]” wraz z translacją słownika MeSH
Dane wejściowe
Zastosowana kwerenda:
## [1] "(mrna vaccine*[Title/Abstract]) AND human[mh]"Translacja MeSH zapytania:
## [1] "(mrna vaccine[Title/Abstract] OR mrna vaccines[Title/Abstract]) AND \"humans\"[MeSH Terms]"Liczba otrzymanych wyników:
## [1] 97Charakterystyka otrzymanego zbioru
Zakres czasowy otrzymanych publikacji obejmuje lata 2009-2020. Do analizy włączono 94 dokumenty, z czego 59 dotyczy publikacji naukowych. Liczba publikacji wzrastała średnio o 33,5% w porównaniu do roku poprzedniego. Najwięcej publikacji zostało opublikowanych w 2020 r. W 2020 r. opublikowano 24 publikacje dotyczące poruszanej tematyki.
| Description | Results |
|---|---|
| Timespan | 2009:2020 |
| Sources (Journals, Books, etc) | 61 |
| Documents | 96 |
| Average years from publication | 3.98 |
| Average citations per documents | 0 |
| Average citations per year per doc | 0 |
| References | 10 |
Roczny wskaźnik wzrostu liczby publikacji
## [1] 34.47264Rozkład publikacji w ujęciu rocznym
Analiza bibliograficzna
Przegląd zawiera 77 artykułów opublikowanych w czasopismach naukowych. 6 publikacji dotyczy badań klinicznych I fazy.
| Description | Results |
|---|---|
| clinical trial, phase i | 6 |
| comparative study | 1 |
| editorial | 2 |
| journal article | 79 |
| letter | 5 |
| news | 3 |
Sieć współpracy naukowej
Sieć współpracy naukowej określa relację, w której obiektami są autorzy, natomiast nicie pomiędzy obiektami oznaczają autorów współtworzących publikację. Kolor oznacza utworzone klastry.
Rozkład produktywności autorów i liczby cytowań w ujęciu rocznym
Wykres przedstawia liczbę publikacji oraz całkowitą liczbę cytowań autorów (top n=10) poszczególnych latach objętych analizą.
Charakterystyka ośrodków naukowych
Liczba artykułów w podziale na źródło publikacji - top n=10
| Sources | Articles |
|---|---|
| MOLECULAR THERAPY : THE JOURNAL OF THE AMERICAN SOCIETY OF GENE THERAPY | 7 |
| EXPERT REVIEW OF VACCINES | 4 |
| METHODS IN MOLECULAR BIOLOGY (CLIFTON N.J.) | 4 |
| THE NEW ENGLAND JOURNAL OF MEDICINE | 4 |
| CELL RESEARCH | 3 |
| FRONTIERS IN IMMUNOLOGY | 3 |
| NATURE | 3 |
| NATURE BIOTECHNOLOGY | 3 |
| BIOMATERIALS | 2 |
| BIOTECHNOLOGY ADVANCES | 2 |
Współwystępowanie słów kluczowych
Analiza CO-WORD
Eksploracja wyrazów ze względu na częstotliwość wystąpień w przeglądzie literatury
Hierarchiczna analiza klastrów HCA
Wysokość klamry osi y wskazuje dystans między klastrami. Im wyższa wysokość połączenia między obserwacjami, tym mniej podobne są do siebie obiekty. Odległość na osi x nie stanowi kryterium podobieństwa.
Analiza struktur pojęciowych
W analizie wykorzystano analizę korespondencji w celu wydobycia struktury pojęciowej wyrazów przez redukcję ich odmian i pochodnych. Na podstawie otrzymanej struktury metodą k-średnich wyznaczono współrzędne k-punktów, będących środkiem klastra. Otrzymane klastry skupiają wyrazy o wspólnych pojęchach zredukowane do ich podstaw lub rdzenia.
Mapa tematyczna
Mapa tematyczna klasyfikuje klastry wyrazów na podstawie stopnia jej wykorzystania w literaturze.
- Prawa górna ćwiartka - terminologia techniczna (niezwiązana bezpośrednio z poruszanym tematem)
- Prawa dolna ćwiartka - terminologia podstawowa (tworząca fundament literatury)
- Lewa górna ćwiartka - terminologia bardzo specjalistyczna lub niszowa
- Lewa dolna ćwiartka- terminologia dodatkowa (terminy związane z analizowanym tematem, które w literaturze pojawiają się fakultatywnie)
Synteza wyników abstraktów
## [[1]]
## [1] " In conclusion, we show here that direct injection of protamine-protected mRNA is feasible and safe."
## [2] " The significant influence of the treatment on the frequency of immunosuppressive cells, the increase of vaccine-directed T cells upon treatment in a subset of patients together with the demonstration of a complete clinical response encourage further clinical investigation of the protamine-mRNA vaccine. DOI: 10.1097/CJI.0b013e3181a00068"
##
## [[2]]
## [1] " RECENT FINDINGS: Conventional as well as self-replicating mRNA vaccines have demonstrated their potential to prevent the induction of an allergic phenotype in terms of allergen-specific IgE, allergy-associated cytokine profiles, eosinophilic lung infiltration, and airway hyperreactivity."
## [2] " Preliminary data raise the question whether TH1 immune deviation induced by mRNA vaccination resembles the natural phenotype of a certain proportion of nonatopic individuals.Reservations regarding Good Manufacturing Practices manufacture costs, shelf life stability, and lack of immunogenicity due to rapid in-vivo degradation have been overcome by novel findings."
## [3] " SUMMARY: mRNA vaccines open the field for a safety-optimized prophylactic vaccination against allergic diseases."
## [4] " Future studies concerning long-term effects and vaccine-induced versus natural immune responses will be needed to transfer this knowledge to the clinics. DOI: 10.1097/ACI.0b013e32833fd5b6"
##
## [[3]]
## [1] " In conclusion, two-component mRNA vaccines with self-adjuvanting activity induce balanced adaptive immune responses and mediate sustained antitumor activity. DOI: 10.1097/CJI.0b013e3181f7dbe8"
##
## [[4]]
## [1] " mRNA vaccination as a safe approach for specific protection from type I allergy. Weiss R(1), Scheiblhofer S, Roesler E, Weinberger E, Thalhamer J. Author information: (1)University of Salzburg, Christian Doppler Laboratory for Allergy Diagnosis & Therapy, Hellbrunnerstrasse 34, 5020 Salzburg, Austria. Allergic diseases are on the increase and current therapies are lacking in efficacy and patient compliance."
## [2] " In recent years, the idea of prophylactic measures, especially for children at high risk for allergy, has become increasingly popular."
## [3] " This review summarizes the available preclinical data for protective allergy vaccines, with a focus on one of the most promising vaccine candidates; mRNA vaccines."
## [4] " Recently, mRNA vaccines have been rediscovered as an alternative to their more prominent counterparts, the DNA vaccines. Allergen-encoding mRNA vaccines elicit long-lasting protection from sensitization, and induce a type of immunity similar to the natural protective response that is acquired in the presence of microbial burden early in life. Owing to their excellent safety profile, they represent the ideal candidates for a vaccine that aims to protect at-risk children who have not yet been sensitized to allergens. DOI: 10.1586/erv.11.168"
##
## [[5]]
## [1] " The two-component mRNA vaccines induce a very fast and boostable immune response."
## [2] " Therefore, the vaccination schedules can be adjusted to suit the clinical situation."
## [3] " Moreover, by combining the mRNA vaccines with therapies in clinical use (chemotherapy or anti-CTLA-4 antibody therapy), an even more effective anti-tumor response can be elicited."
## [4] " The first clinical data obtained from two separate Phase I/IIa trials conducted in PCA (prostate cancer) and NSCLC (non-small cell lung carcinoma) patients have shown that the two-component mRNA vaccines are safe, well tolerated and highly immunogenic in humans. Copyright © 2012 John Wiley & Sons, Ltd. DOI: 10.1002/jgm.2605"
##
## [[6]]
## [1] " Based on in situ protein expression, mRNA vaccines are capable of inducing a balanced immune response comprising both cellular and humoral immunity while not subject to MHC haplotype restriction."
## [2] " In addition, mRNA is an intrinsically safe vector as it is a minimal and only transient carrier of information that does not interact with the genome."
## [3] " Because any protein can be expressed from mRNA without the need to adjust the production process, mRNA vaccines also offer maximum flexibility with respect to development."
## [4] " Taken together, mRNA presents a promising vector that may well become the basis of a game-changing vaccine technology platform. Here, we outline the current knowledge regarding different aspects that should be considered when developing an mRNA-based vaccine technology. DOI: 10.4161/rna.22269 PMCID: PMC3597572"
##
## [[7]]
## [1] " Here we show that mRNA vaccines induce balanced, long-lived and protective immunity to influenza A virus infections in even very young and very old mice and that the vaccine remains protective upon thermal stress."
## [2] " This vaccine format elicits B and T cell-dependent protection and targets multiple antigens, including the highly conserved viral nucleoprotein, indicating its usefulness as a cross-protective vaccine."
## [3] " In ferrets and pigs, mRNA vaccines induce immunological correlates of protection and protective effects similar to those of a licensed influenza vaccine in pigs."
## [4] " Thus, mRNA vaccines could address substantial medical need in the area of influenza prophylaxis and the broader realm of anti-infective vaccinology. DOI: 10.1038/nbt.2436"
##
## [[8]]
## NULL
##
## [[9]]
## [1] " This greatly reduces general complications associated with biological vaccine production, such as handling of infectious agents, genetic variability, environmental risks, or restrictions to vaccine distribution. (3) RNA can be tailored to provide potent adjuvant stimuli to the innate immune system by direct activation of RNA-specific receptors; this may reduce the need for additional adjuvants."
## [2] " The formation of native antigen in situ affords great versatility, including intracellular localization, membrane association, posttranslational modification, supra-molecular assembly, or targeted structural optimization of delivered antigen."
## [3] " Messenger RNA vaccines induce balanced immune responses including B cells, helper T cells, and cytotoxic T lymphocytes, rendering them an extremely adaptable platform."
## [4] " This article surveys the design, mode of action, and capabilities of state-of-the-art mRNA vaccines, focusing on the paradigm of influenza prophylaxis. Copyright © 2013 John Wiley & Sons, Ltd. DOI: 10.1002/wrna.1189"
##
## [[10]]
## [1] " Whereas initial studies were limited to the ex vivo loading of dendritic cells (DCs) with antigen-encoding mRNA, recent progress has led to the development of improved mRNA vaccines that enable direct in vivo targeting of DCs."
## [2] " Although preclinical studies demonstrated their potency in inducing antitumor immunity, several bottlenecks hinder the broader application of mRNA vaccines."
## [3] " In this review, we discuss the challenges associated with mRNA-based vaccination strategies, the technological advances that have been made to overcome these limitations, and the hurdles that remain to be tackled for the development of an optimal mRNA vaccine. Copyright © 2013 Elsevier Ltd."
## [4] " All rights reserved. DOI: 10.1016/j.molmed.2013.09.002"
##
## [[11]]
## [1] " As an alternative to allergen-specific immunotherapy, prophylactic vaccination against type I allergic diseases could slow down or even stop the progress of the allergy pandemic."
## [2] " Allergen-encoding gene-based vaccines, i.e., plasmid DNA and mRNA vaccines, provide the advantage of purity over crude allergen extracts, which involve the risk of de novo sensitizations."
## [3] " Furthermore, these formulations have been demonstrated to induce T helper 1 as well as T regulatory immune responses--a pre-requisite for prophylactic intervention against allergies."
## [4] " However, prophylactic vaccines against environmental allergens strikingly differ from conventional vaccines against infectious diseases or therapeutic approaches concerning the underlying immunological mechanisms. DOI: 10.4161/hv.27183 PMCID: PMC4130253"
##
## [[12]]
## [1] " Curevacs' mRNA containing vaccines (RNActive®) combine the beneficial properties of sufficient antigen-expression, autologous immune-stimulation and a high flexibility with respect to production and application."
## [2] " CV9103 and CV9104 are novel RNActive®-derived anticancer vaccines for the treatment of patients with prostate cancer."
## [3] " After successful phase I/II studies with documentation of good tolerability and favorable immune-activation of CV9103, the vaccine CV9104 is currently undergoing clinical testing in specific clinical settings such as castration resistant prostate cancer and as a neoadjuvant agent in men with high risk prostate cancer prior to surgery."
## [4] " This review discusses the available preclinical and clinical data on the anticancer vaccination treatment with RNActive®-derived anticancer-vaccines CV9103 and CV9104. DOI: 10.4161/hv.29553 PMCID: PMC4514038"
##
## [[13]]
## [1] " Like other types of nucleic acid vaccines, mRNA vaccines have the potential to combine the positive attributes of live attenuated vaccines while obviating many potential safety limitations."
## [2] " Although data from initial clinical trials appear encouraging, mRNA vaccines are far from a commercial product."
## [3] " These initial approaches have spurred innovations in vector design, non-viral delivery, large-scale production and purification of mRNA to quickly move the technology forward."
## [4] " Some improvements have already been tested in preclinical models for both prophylactic and therapeutic vaccine targets and have demonstrated their ability to elicit potent and broad immune responses, including functional antibodies, type 1 T helper cells-type T cell responses and cytotoxic T cells. Though the initial barriers for this nucleic acid vaccine approach seem to be overcome, in our opinion, the future and continued success of this approach lies in a more extensive evaluation of the many non-viral delivery systems described in the literature and gaining a better understanding of the mechanism of action to allow rational design of next generation technologies. DOI: 10.1517/17425247.2014.901308"
##
## [[14]]
## [1] " Although antigen-specific immunotherapy induced by therapeutic HPV vaccines was proved extremely efficacious in pre-clinical models, its progression through clinical trials suffered poor responses in the initial trials."
## [2] " Later attempts seem to have been more promising, particularly against the well-defined precursors of cervical, anal or vulvar cancer, where the local immunosuppressive milieu is less active."
## [3] " This review focuses on the advances made in these fields, highlighting several new technologies (such as mRNA vaccine, plant-derived vaccine)."
## [4] " The most promising immunotherapies used in clinical trials are also summarized, along with integrated strategies, particularly promising in controlling tumor metastasis and in eliminating cancer cells altogether.After the early promising clinical results, the development of therapeutic HPV vaccines need to be implemented and applied to the users in order to eradicate HPV-associated malignancies, eradicating existing perception (after the effectiveness of commercial preventive vaccines) that we have already solved the problem. DOI: 10.1186/1756-9966-33-29 PMCID: PMC3986944"
##
## [[15]]
## [1] " Pharmacodynamic analyses include the assessment of immune responses to the antigens encoded by CV9202 and others not included in the panel (antigen spreading) and standard efficacy assessments."
## [2] " DISCUSSION: RNActive self-adjuvanted mRNA vaccines offer the potential for simultaneously inducing immune responses to a wide panel of antigens commonly expressed in tumors."
## [3] " This trial will assess the feasibility of this approach in combination with local radiotherapy in NSCLC patients."
## [4] " TRIAL REGISTRATION: Clinicaltrials.gov: NCT01915524/EudraCT No.: 2012-004230-41. DOI: 10.1186/1471-2407-14-748 PMCID: PMC4195907"
##
## [[16]]
## [1] " Today, these issues are no longer perceived as barriers in the widespread implementation of the technology."
## [2] " Currently, nonamplifying mRNA vaccines are under investigation in human clinical trials and can be produced at a sufficient quantity and quality to meet regulatory requirements."
## [3] " If the encouraging preclinical data with self-amplifying mRNA vaccines are matched by equivalently positive immunogenicity, potency, and tolerability in human trials, this platform could establish nucleic acid vaccines as a versatile new tool for human immunization. Copyright © 2015 Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/bs.adgen.2014.10.005"
##
## [[17]]
## [1] " Although immune responses are generated by naked mRNAs, their formulations with chemical carriers are expected to provide more specificity and internalization in dendritic cells (DCs) for better immune responses and dose reduction."
## [2] " This review reports lipid-based formulations (LBFs) that have proved preclinical efficacy."
## [3] " The selective delivery of mRNA LBFs to favor intracellular accumulation in DCs and reduction of the effective doses is discussed, notably to decorate LBFs with carbohydrates or glycomimetics allowing endocytosis in DCs."
## [4] " We also report how smart intracellular delivery is achieved using pH-sensitive lipids or polymers for an efficient mRNA escape from endosomes and limitations regarding cytosolic mRNA location for translation. DOI: 10.1586/14760584.2015.986104"
##
## [[18]]
## [1] " Current Developments in Actively Personalized Cancer Vaccination with a Focus on RNA as the Drug Format. Diken M, Kreiter S, Kloke B, Sahin U. Developments in sequencing technologies have not only led to a rapid generation of genomic and transcriptional data from cancer patients, but also revealed the vast diversity of cancer-specific changes in patient tumors."
## [2] " Among these, mutation changes in the protein sequence can result in novel epitopes recognized by the immune system and, therefore, can be employed in the development of personalized vaccines."
## [3] " Thanks to its easy design and scalable GMP production, vaccines based on mRNAs coding for mutated epitopes have emerged as a reliable strategy for the exploitation of the potential of patient-specific genomic data. In this review, we provide an overview of recent developments in actively personalized vaccinations, with a special focus on the promise of mRNA vaccines. © 2015 S."
## [4] " Karger AG, Basel. DOI: 10.1159/000437184"
##
## [[19]]
## [1] " RNA-Based Vaccines in Cancer Immunotherapy. McNamara MA(1), Nair SK(2), Holl EK(3). Author information: (1)Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. (2)Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA ; Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. (3)Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. RNA vaccines traditionally consist of messenger RNA synthesized by in vitro transcription using a bacteriophage RNA polymerase and template DNA that encodes the antigen(s) of interest."
## [2] " Once administered and internalized by host cells, the mRNA transcripts are translated directly in the cytoplasm and then the resulting antigens are presented to antigen presenting cells to stimulate an immune response."
## [3] " Alternatively, dendritic cells can be loaded with either tumor associated antigen mRNA or total tumor RNA and delivered to the host to elicit a specific immune response."
## [4] " In this review, we will explain why RNA vaccines represent an attractive platform for cancer immunotherapy, discuss modifications to RNA structure that have been developed to optimize mRNA vaccine stability and translational efficiency, and describe strategies for nonviral delivery of mRNA vaccines, highlighting key preclinical and clinical data related to cancer immunotherapy. DOI: 10.1155/2015/794528 PMCID: PMC4668311"
##
## [[20]]
## [1] " Mutanome Engineered RNA Immunotherapy: Towards Patient-Centered Tumor Vaccination. Vormehr M(1), Schrörs B(2), Boegel S(2), Löwer M(2), Türeci Ö(2), Sahin U(3). Author information: (1)Research Center for Immunotherapy (FZI), Langenbeckstr. 1, Building 708, 55131 Mainz, Germany; Biopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, 55131 Mainz, Germany. (2)TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University, Freiligrathstr. 12, 55131 Mainz, Germany. (3)Research Center for Immunotherapy (FZI), Langenbeckstr. 1, Building 708, 55131 Mainz, Germany; Biopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, 55131 Mainz, Germany; TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University, Freiligrathstr. 12, 55131 Mainz, Germany. Advances in nucleic acid sequencing technologies have revolutionized the field of genomics, allowing the efficient targeting of mutated neoantigens for personalized cancer vaccination."
## [2] " Due to their absence during negative selection of T cells and their lack of expression in healthy tissue, tumor mutations are considered as optimal targets for cancer immunotherapy."
## [3] " Preclinical and early clinical data suggest that synthetic mRNA can serve as potent drug format allowing the cost efficient production of highly efficient vaccines in a timely manner."
## [4] " In this review, we describe a process, which integrates next generation sequencing based cancer mutanome mapping, in silico target selection and prioritization approaches, and mRNA vaccine manufacturing and delivery into a process we refer to as MERIT (mutanome engineered RNA immunotherapy). DOI: 10.1155/2015/595363 PMCID: PMC4710911"
##
## [[21]]
## [1] " AREAS COVERED: This editorial highlights the key milestones in the discovery and development of self-amplifying mRNA vaccines, and reviews how they might be used as a rapid response platform."
## [2] " The paper points out how future improvements in RNA vector design and non-viral delivery may lead to decreases in effective dose and increases in production capacity."
## [3] " EXPERT OPINION: The prospects for non-viral delivery of self-amplifying mRNA vaccines are very promising."
## [4] " Like other types of nucleic acid vaccines, these vaccines have the potential to draw on the positive attributes of live-attenuated vaccines while obviating many potential safety limitations. Hence, this approach could enable the concept of vaccines on demand as a rapid response to a real threat rather than the deployment of strategic stockpiles based on epidemiological predictions for possible threats. DOI: 10.1517/17460441.2015.996128"
##
## [[22]]
## [1] " Encouraged by these findings, we established a process by which mutations identified by exome sequencing could be selected as vaccine targets solely through bioinformatic prioritization on the basis of their expression levels and major histocompatibility complex (MHC) class II-binding capacity for rapid production as synthetic poly-neo-epitope messenger RNA vaccines."
## [2] " We show that vaccination with such polytope mRNA vaccines induces potent tumour control and complete rejection of established aggressively growing tumours in mice."
## [3] " Moreover, we demonstrate that CD4(+) T cell neo-epitope vaccination reshapes the tumour microenvironment and induces cytotoxic T lymphocyte responses against an independent immunodominant antigen in mice, indicating orchestration of antigen spread."
## [4] " Finally, we demonstrate an abundance of mutations predicted to bind to MHC class II in human cancers as well by employing the same predictive algorithm on corresponding human cancer types. Thus, the tailored immunotherapy approach introduced here may be regarded as a universally applicable blueprint for comprehensive exploitation of the substantial neo-epitope target repertoire of cancers, enabling the effective targeting of every patient's tumour with vaccines produced 'just in time'. DOI: 10.1038/nature14426 PMCID: PMC4838069"
##
## [[23]]
## [1] " Apart from being used directly to vaccinate patients, mRNAs can also be used in cellular therapies to transfect patient-derived cells in vitro and infuse the manipulated cells back into the patient."
## [2] " One such application is the transfection of patient-derived dendritic cells (DCs) with mRNAs encoding TAAs, which leads to the presentation of TAA-derived peptides on the DCs and an activation of antigen-specific T cells in vivo."
## [3] " A second application is the transfection of patient-derived T cells with mRNAs encoding chimeric antigen receptors, which allows the T cells to directly recognize a specific antigen expressed on the tumor."
## [4] " In this chapter, we will review preclinical and clinical data for the different approaches. DOI: 10.1007/978-3-319-42934-2_5"
##
## [[24]]
## [1] " Our data demonstrate that E7-TriMix mRNA vaccine-induced CD8(+) T lymphocytes migrate into the tumour nest and control tumour growth, although they do not express mucosa-associated markers such as CD103 or CD49a."
## [2] " We additionally show that despite the presence of the antigen-specific T cells in the tumour lesions, the therapeutic outcomes in the genital tract model remain limited."
## [3] " Here, we report that such a hostile tumour microenvironment can be reversed by cisplatin treatment, leading to a complete regression of clinically relevant tumours when combined with mRNA immunization."
## [4] " We thereby demonstrate the necessity of utilizing clinically relevant models for preclinical evaluation of anticancer therapies and the importance of a simultaneous combination of anticancer immune response induction with targeting of tumour environment. DOI: 10.1038/srep22509 PMCID: PMC4773884"
##
## [[25]]
## [1] " The delivery vehicle containing CP 2k and mRNA overcame the epithelial barrier by reversibly opening the tight junctions, enhanced the paracellular delivery of mRNA and consequently minimized absorption of toxins in the nasal cavity. Together with the excellent intracellular delivery and prolonged nasal residence time, strong system and mucosal anti-HIV immune responses as well as cytokine productions were achieved with a balanced Th1/Th2/Th17 type."
## [2] " Our study provided the first proof of evidence that cationic polymers can be used as safe and potent intranasal mRNA vaccine carriers to overcome the nasal epithelial barrier."
## [3] " The safe and versatile polymeric delivery system represents a promising vaccination platform for infectious diseases. Copyright © 2016 Elsevier B.V."
## [4] " All rights reserved. DOI: 10.1016/j.jconrel.2016.02.043"
##
## [[26]]
## [1] " They promise the flexibility of plasmid DNA vaccines, without the need for electroporation, but with enhanced immunogenicity and safety."
## [2] " In addition, they avoid the limitations of anti-vector immunity seen with viral vectors, and can be dosed repeatedly."
## [3] " This review highlights the key papers published over the past few years and summarizes prospects for the near future. Copyright © 2016 Elsevier Ltd."
## [4] " All rights reserved. DOI: 10.1016/j.coi.2016.05.008"
##
## [[27]]
## [1] " Inhibition of viral replication by vaccination was verified by qRT-PCR."
## [2] " Furthermore, we demonstrate that CD4+ T cells are crucial for the generation of neutralizing antibodies."
## [3] " In domestic pigs we were able to induce VN titers that correlate with protection in adult and newborn pigs."
## [4] " This study demonstrates the feasibility of a non-replicating mRNA rabies vaccine in small and large animals and highlights the promises of mRNA vaccines for the prevention of infectious diseases. DOI: 10.1371/journal.pntd.0004746 PMCID: PMC4918980"
##
## [[28]]
## [1] " Here, we demonstrate that mRNA lipoplexes induce a potent type I interferon (IFN) response upon subcutaneous, intradermal and intranodal injection."
## [2] " Regardless of the route of immunization applied, these type I IFNs interfered with the generation of potent cytolytic T cell responses."
## [3] " Most importantly, blocking type I IFN signaling at the site of immunization through the use of an IFNAR blocking antibody greatly enhanced the prophylactic and therapeutic antitumor efficacy of mRNA lipoplexes in the highly aggressive B16 melanoma model."
## [4] " As type I IFN induction appears to be inherent to the mRNA itself rather than to unique properties of the mRNA lipoplex formulation, preventing type I IFN induction and/or IFNAR signaling at the site of immunization might constitute a widely applicable strategy to improve the potency of mRNA vaccination. DOI: 10.1038/mt.2016.161 PMCID: PMC5154477"
##
## [[29]]
## [1] " The simplicity of mRNA vaccines greatly reduces complications generally associated with the production of biological vaccines."
## [2] " Intrinsic costimulatory and inflammatory triggers in addition to the provision of the antigenic information makes mRNA an all- in-one molecule that does not need additional adjuvants and that does not pose the risk of genomic integration."
## [3] " Clinical studies in various cancer types are moving forward and promising results with favorable clinical outcome are awaited."
## [4] " This review will recapitulate conceptual, mechanistic and immune-related features of this highly versatile molecule, elucidate how these features have been addressed in the past, and how comprehensive understanding can foster further optimization for broad application possibilities in cancer treatment. DOI: 10.21775/cimb.022.113"
##
## [[30]]
## [1] " In conclusion, the lipid nanoparticle formulation presented here is a promising vector for mRNA vaccine delivery, one that is capable of inducing a strong cytotoxic T cell response."
## [2] " Further optimization, including the incorporation of different adjuvants, will likely enhance the potency of the vaccine. DOI: 10.1021/acs.nanolett.6b03329 PMCID: PMC5523404"
##
## [[31]]
## [1] " Methods Mol Biol. 2017;1499:143-153. doi: 10.1007/978-1-4939-6481-9_8. Measuring the Adjuvant Activity of RNA Vaccines. Pardi N(1), Weissman D(2). Author information: (1)Department of Medicine, University of Pennsylvania, 52 Johnson Pavilion, Philadelphia, PA, 19104, USA. (2)Department of Medicine, University of Pennsylvania, 52 Johnson Pavilion, Philadelphia, PA, 19104, USA. dreww@mail.med.upenn.edu. mRNA has recently arisen as a promising new drug class with the potential to be applied to various therapeutic modalities, including protein replacement and vaccination against cancer and infectious diseases."
## [2] " Numerous approaches have been pursued to develop potent mRNA vaccines, many of them have proved to be successful and have already entered human clinical trials."
## [3] " RNA, especially in vitro transcribed, is extremely immunogenic as it induces innate immune responses through the activation of a variety of pattern recognition receptors. This feature of RNA is potentially beneficial for vaccine development, where antigen-encoding RNA might also function as an adjuvant to elicit potent antigen-specific T and B cell immune responses."
## [4] " Here, we describe the methods that can be used to evaluate the immunogenicity of RNA vaccines in vitro and in vivo. DOI: 10.1007/978-1-4939-6481-9_8"
##
## [[32]]
## NULL
##
## [[33]]
## [1] " In the EU no regulatory guidelines presently exist that specifically address mRNA-based vaccines."
## [2] " The existing regulatory framework, however, clearly defines that mRNA-based vaccines in most cases have to be centrally approved."
## [3] " Interestingly, depending on whether RNA-based vaccines are directed against tumors or infectious disease, they are formally considered gene therapy products or not, respectively."
## [4] " Besides an overview on the current clinical use of mRNA vaccines in various therapeutic areas a detailed discussion of the current regulatory situation is provided and regulatory perspectives are discussed. DOI: 10.1007/978-1-4939-6481-9_13"
##
## [[34]]
## [1] " Considerations for Producing mRNA Vaccines for Clinical Trials. Schmid A(1). Author information: (1)University of Applied Sciences Albstadt-Sigmaringen, Anton-GĂĽnther-Str. 51, 72488, Sigmaringen, Germany. schmida@hs-albsig.de. The approval of clinical trials by the competent authorities requires comprehensive quality documentation on the new drug to be used on the clinical trial participant."
## [2] " In the EU quality data is summarized as Investigational Medicinal Product Dossier (IMPD), in the USA as Investigational New Drug (IND) Application."
## [3] " For that, several preconditions concerning production, quality control, and assurance have to be fulfilled."
## [4] " Here, specific requirements related to mRNA vaccines are addressed on the basis of European standards. DOI: 10.1007/978-1-4939-6481-9_15"
##
## [[35]]
## [1] " Induction of T-cell immunity is a multi-faceted process comprising antigen acquisition, antigen processing and presentation, as well as immune stimulation."
## [2] " The effectiveness of mRNA vaccines is critically dependent on making the antigen(s) of interest available to professional antigen-presenting cells, especially DCs."
## [3] " Efficient delivery of mRNA into DCs in vivo remains a major challenge in the mRNA vaccine field."
## [4] " This review summarizes the principles of mRNA vaccines and highlights the importance of in vivo mRNA delivery and recent advances in harnessing their therapeutic potential. DOI: 10.1007/82_2017_509"
##
## [[36]]
## [1] " CONCLUSION: This translational approach not only allowed for identification of the basic mechanisms of self-adjuvantation from the mRNA vaccine but also for comparison of the response across species, a response that appears relatively conserved or at least convergent between the in vitro human and in vivo mouse models. DOI: 10.1186/s12967-016-1111-6 PMCID: PMC5210268"
##
## [[37]]
## [1] " The mechanisms behind this duality are unclear."
## [2] " Disentangling the factors governing the beneficial or detrimental impact of type I IFNs on CD8+ T cell responses is vital to the design of mRNA vaccines of increased potency."
## [3] " In light of recent advancements regarding the complex role of type I IFNs in regulating CD8+ T cell immunity to infectious diseases, we posit that the dual outcome of type I IFNs on CD8+ T cell responses to mRNA vaccination is determined by the timing and intensity of type I IFN induction relative to T cell receptor (TCR) activation. Copyright © 2017 Elsevier Ltd."
## [4] " All rights reserved. DOI: 10.1016/j.molmed.2017.01.006"
##
## [[38]]
## NULL
##
## [[39]]
## [1] " Interim results from a first-in-human, escalating-dose, phase 1 H10N8 study show very high seroconversion rates, demonstrating robust prophylactic immunity in humans. Adverse events (AEs) were mild or moderate with only a few severe and no serious events."
## [2] " These data show that LNP-formulated, modified mRNA vaccines can induce protective immunogenicity with acceptable tolerability profiles. Copyright © 2017 The Authors."
## [3] " Published by Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/j.ymthe.2017.03.035 PMCID: PMC5475249"
##
## [[40]]
## [1] " For over two decades, researchers have been trying to overcome major challenges for utilizing such RNAs in a therapeutic context, including intracellular delivery, stability, and immune response activation."
## [2] " This research is finally beginning to bear fruit as the first RNA drugs gain FDA approval and more advance to the final phases of clinical trials."
## [3] " Furthermore, the recent advent of CRISPR, an RNA-guided gene-editing technology, as well as new strides in the delivery of messenger RNA transcribed in vitro, have triggered a major expansion of the RNA-therapeutics field."
## [4] " In this review, we discuss the challenges for clinical translation of RNA-based therapeutics, with an emphasis on recent advances in delivery technologies, and present an overview of the applications of RNA-based drugs for modulation of gene/protein expression and genome editing that are currently being investigated both in the laboratory as well as in the clinic. DOI: 10.1186/s13073-017-0450-0 PMCID: PMC5485616"
##
## [[41]]
## [1] " We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus."
## [2] " Vaccinated dams challenged with a heterologous ZIKV strain at embryo day 6 (E6) and evaluated at E13 showed markedly diminished levels of viral RNA in maternal, placental, and fetal tissues, which resulted in protection against placental damage and fetal demise."
## [3] " As modified mRNA and live-attenuated vaccine platforms can restrict in utero transmission of ZIKV in mice, their further development in humans to prevent congenital ZIKV syndrome is warranted. Copyright © 2017 Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/j.cell.2017.06.040 PMCID: PMC5546158"
##
## [[42]]
## NULL
##
## [[43]]
## [1] " Live vaccines that may be contraindicated in pregnancy are also in development for potential inclusion in national immunization programmes in childhood or pre-teenage age groups."
## [2] " WHO developed a target product profile for Zika vaccines for use in an emergency."
## [3] " Expert commentary: Although ZIKV vaccine development had a quick head start, further development may be hampered because of the inability to conduct large efficacy trials with the decline in cases globally and unpredictability of new outbreaks."
## [4] " Furthermore, there are complex ethical issues involved in conducting efficacy trials in pregnant women. DOI: 10.1080/14760584.2017.1345309"
##
## [[44]]
## [1] " Several forms of ZIKV VLPs have been reported featuring the co-expression of the prM-E, prM-E-NS1, C-prM-E, and NS2B/NS3 viral genes in human cells."
## [2] " To minimize the effect of the cross-reactive ADE-facilitating antibodies between ZIKV and DENV, several novel mutations have been reported either in or near the FL of DII or DIII to dampen the production of cross-reactive antibodies."
## [3] " Future ZIKV vaccine design efforts should be focused on eliciting improved neutralizing antibodies with a reduced level of cross-reactivity to confer sterilizing immunity. Copyright © 2017 Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/j.biotechadv.2017.09.004"
##
## [[45]]
## [1] " We also demonstrated that mRNA:pU activation of mouse and human dendritic cells was significantly more effective than activation using single stranded mRNA."
## [2] " In vivo mouse immunization experiments using ovalbumin showed that mRNA:pU significantly enhanced the intensity of specific cellular and humoral immune responses, compared to single stranded mRNA."
## [3] " Our novel mRNA:pU formulation can be delivered using a variety of mRNA carriers depending on the purpose and delivery route, providing a versatile platform for improving mRNA vaccine efficiency. Copyright © 2017 Elsevier Ltd."
## [4] " All rights reserved. DOI: 10.1016/j.biomaterials.2017.09.033"
##
## [[46]]
## [1] " The enhanced TÂ cell response had a profound inhibitory effect on tumor growth and metastasis."
## [2] " Generally, the work provided a paradigm for the development of an mRNA vaccine carrier to boost the anticancer immune response. Copyright © 2017 The American Society of Gene and Cell Therapy."
## [3] " Published by Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/j.ymthe.2017.11.009 PMCID: PMC5835019"
##
## [[47]]
## [1] " In vivo studies demonstrated that the NP-based mRNA vaccine, targeted to mannose receptors on DCs, could successfully express tumor antigen in the DCs of the lymph node; that the NP vaccine could induce a strong, antigen-specific, in vivo cytotoxic T lymphocyte response against TNBC 4T1 cells; and that combination immunotherapy of the vaccine and anti-CTLA-4 monoclonal antibody could significantly enhance anti-tumor immune response compared to the vaccine or monoclonal antibody alone."
## [2] " These data support both the NP as a carrier for delivery of mRNA vaccine and a potential combination immunotherapy of the NP-based mRNA vaccine and the CTLA-4 inhibitor for TNBC. Copyright © 2017 The American Society of Gene and Cell Therapy."
## [3] " Published by Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/j.ymthe.2017.10.020 PMCID: PMC5763160"
##
## [[48]]
## [1] " When sa-RNA was combined in a trivalent formulation, it protected against sequential H1N1 and H3N2 challenges."
## [2] " From this we conclude that sa-RNA is a promising platform for vaccines against viral diseases. Copyright © 2017 The Authors."
## [3] " Published by Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/j.ymthe.2017.11.017 PMCID: PMC5835025"
##
## [[49]]
## NULL
##
## [[50]]
## [1] "2018 Jan 12. mRNA vaccines - a new era in vaccinology. Pardi N(1), Hogan MJ(1), Porter FW(2), Weissman D(1). Author information: (1)Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. (2)Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina 27710, USA. mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration."
## [2] " However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA."
## [3] " Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans."
## [4] " This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use. DOI: 10.1038/nrd.2017.243 PMCID: PMC5906799"
##
## [[51]]
## [1] " Since the protective correlates in pregnant women and transplant recipients may differ, we developed an additional mRNA vaccine expressing the immunodominant CMV T cell antigen pp65."
## [2] " Administration of pp65 vaccine with PC and gB elicited robust multi-antigenic T cell responses in mice."
## [3] " Our data demonstrate that mRNA/LNP is a versatile platform that enables the development of vaccination strategies that could prevent CMV infection and consequent disease in different target populations. Copyright © 2018 The Author(s)."
## [4] " Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.vaccine.2018.01.029"
##
## [[52]]
## [1] "Apr 24. Current Status of Messenger RNA Delivery Systems. Stanton MG(1). Author information: (1)Generation Bio , Cambridge, Massachusetts. Messenger RNA is emerging as a highly versatile biological construct for creation of impactful medicines. mRNA vaccines directed toward infectious disease and cancer are in clinical development with encouraging early reads on tolerability and efficacy."
## [2] " The use of mRNA to direct intense but transient expression of paracrine factors is finding utility in reprogramming progenitor cells for wound healing and cardiac regeneration and for stimulation of antitumor immune responses, at least preclinically as we await clinical results. The use of mRNA for prolonged and repeated expression of proteins and enzymes to treat rare, typically monogenic disease is nearing clinical entry."
## [3] " These uses of mRNA require delivery solutions, and the application of and improvement to existing nanoparticle nucleic acid delivery systems have jump started the pace of development and reenergized the field of particle based nucleic acid delivery."
## [4] " The current status of mRNA delivery is reviewed in this article with an eye toward clinical tractability. DOI: 10.1089/nat.2018.0726"
##
## [[53]]
## [1] " Here we describe the development and evaluation of a versatile and highly efficient mRNA vaccine-delivery system that employs charge-altering releasable transporters (CARTs) to deliver antigen-coding mRNA to antigen-presenting cells (APCs)."
## [2] " We demonstrate in human peripheral blood mononuclear cells that CART vaccines can activate a robust antigen-specific immune response against mRNA-encoded viral epitopes."
## [3] " In an established mouse model, we demonstrate that CARTs preferentially target professional APCs in secondary lymphoid organs upon i.v. injections and target local APCs upon s.c. injection."
## [4] " Finally, we show that CARTs coformulated with mRNA and a Toll-like receptor ligand simultaneously transfect and activate target cells to generate an immune response that can treat and cure mice with large, established tumors. DOI: 10.1073/pnas.1810002115 PMCID: PMC6166849"
##
## [[54]]
## [1] " 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."
## [2] " What is more, the emergence of antibiotic resistant bacteria calls for new approaches to prevent infections."
## [3] " 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."
## [4] " 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. DOI: 10.3389/fimmu.2018.01963 PMCID: PMC6156540"
##
## [[55]]
## [1] " Moreover, by targeting the encoded allergen to subcellular compartments for degradation, release of native allergen can be avoided."
## [2] " Due to inherent safety features, mRNA vaccines could be the candidates of choice for preventive allergy immunizations."
## [3] " The subtle priming of T helper 1 immunity induced by this vaccine type closely resembles responses of non-allergic individuals and-by boosting via natural allergen exposure-could suffice for long-term protection from type I allergy. © 2018 The Authors."
## [4] " Pediatric Allergy and Immunology Published by John Wiley & Sons Ltd. DOI: 10.1111/pai.12964 PMCID: PMC6283005"
##
## [[56]]
## [1] " The formulations are assembled in two steps: (1) formation of a polyplex between mRNAs and amphipathic cationic peptides (RALA, LAH4 or LAH4-L1), and (2) adsorption of polyplexes onto PLA-NPs. LAH4-L1/mRNA polyplexes and PLA-NP/LAH4-L1/mRNA nanocomplexes are taken up by DCs via phagocytosis and clathrin-dependent endocytosis, and induce strong protein expression in DCs in vitro."
## [2] " They modulate DC innate immune response by activating both endosome and cytosolic Pattern Recognition Receptors (PRRs), and induce markers of adaptive responses in primary human DCs in vitro, with prevalent Th1 signature."
## [3] " Thus, LAH4-L1/mRNA and PLA-NP/LAH4-L1/mRNA represent a promising platform for ex vivo treatment and mRNA vaccine development. Copyright © 2018 Elsevier Ltd."
## [4] " All rights reserved. DOI: 10.1016/j.biomaterials.2018.12.019"
##
## [[57]]
## [1] " Recently, mRNA emerged as a promising alternative to traditional vaccine strategies due to its high immunogenicity, suitability for large-scale and low-cost production, and superior safety profile."
## [2] " However, the clinical application of mRNA-based anti-cancer vaccines has been limited by their instability and inefficient in vivo delivery."
## [3] " Recent technological advances have now largely overcome these issues and lipid-based vectors have demonstrated encouraging results as mRNA vaccine platforms against several types of cancers."
## [4] " This review intends to provide a detailed overview of lipid-based vectors for the development of therapeutic mRNA-based anti-tumor vaccines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. DOI: 10.2174/1381612825666190619150221"
##
## [[58]]
## [1] " In addition, mRNA vaccines have the potential to streamline vaccine discovery and development, and facilitate a rapid response to emerging infectious diseases."
## [2] " In this review, we overview the unique attributes of mRNA vaccine approaches, review the data of mRNA vaccines against infectious diseases, discuss the current challenges, and highlight perspectives about the future of this promising technology. Copyright © 2019 The American Society of Gene and Cell Therapy."
## [3] " Published by Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/j.ymthe.2019.01.020 PMCID: PMC6453507"
##
## [[59]]
## [1] " The clinical translation of mRNA therapeutics has been made possible through advances in the design of mRNA manufacturing and intracellular delivery methods."
## [2] " However, broad application of mRNA is still limited by the need for improved delivery systems."
## [3] " In this review, we discuss the challenges for clinical translation of mRNA-based therapeutics, with an emphasis on recent advances in biomaterials and delivery strategies, and we present an overview of the applications of mRNA-based delivery for protein therapy, gene editing, and vaccination. Copyright © 2019."
## [4] " Published by Elsevier Inc. DOI: 10.1016/j.ymthe.2019.02.012 PMCID: PMC6453548"
##
## [[60]]
## NULL
##
## [[61]]
## [1] " Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Atlanta, GA, USA. philip.santangelo@bme.gatech.edu. Comment in Nat Biomed Eng. 2019 May;3(5):331-332. Visualization of the spatio-temporal trafficking of vaccines after their delivery would help evaluate the efficacy of candidate formulations and aid their rational design for preclinical and translational studies."
## [2] " Here, we show that a dual radionuclide-near-infrared probe allows for quantitative, longitudinal and non-invasive monitoring, via positron emission tomography-computed tomography and near-infrared imaging of cynomolgus macaques, of the trafficking dynamics to draining lymph nodes of a model messenger RNA vaccine labelled with the probe."
## [3] " After intramuscular administration of the vaccine to the monkeys, we observed the dynamics of the mRNA vaccine at the injection site and in the draining lymph nodes, performed cellular analyses of the involved tissues using flow cytometry and identified through immunofluorescence that professional antigen-presenting cells are the primary cells containing the injected mRNA and encoding the antigen."
## [4] " This approach may reveal spatio-temporal determinants of vaccine efficacy in preclinical and translational studies employing large mammals. DOI: 10.1038/s41551-019-0378-3"
##
## [[62]]
## [1] " New Vaccine Design and Delivery Technologies. Kanekiyo M(1), Ellis D(2)(3), King NP(2)(4). Author information: (1)Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. (2)Institute for Protein Design, University of Washington, Seattle. (3)Graduate Program in Molecular and Cellular Biology, University of Washington, Seattle. (4)Department of Biochemistry, University of Washington, Seattle. Technological advances in immunology, protein design, and genetic delivery have unlocked new possibilities for vaccine concepts and delivery technologies that were previously inaccessible."
## [2] " These next-generation vaccine design efforts are particularly promising in their potential to provide solutions to challenging targets for which conventional approaches have proven ineffective-for example, a universal influenza vaccine."
## [3] " In this perspective, we discuss emerging approaches to vaccine design and engineering based on recent insights into immunology, structural biology, computational biology, and immunoengineering."
## [4] " We anticipate that these cutting-edge, interdisciplinary approaches will lead to breakthrough vaccine concepts for ever-evolving and (re)emerging influenza viruses, with important ramifications for global public health. Published by Oxford University Press for the Infectious Diseases Society of America 2019. DOI: 10.1093/infdis/jiy745 PMCID: PMC6452296"
##
## [[63]]
## [1] " We show that the proposed λN-Î\262Lac chimeric protein specifically targets its cognate RNA aptamer, boxB, using both gel shift and biolayer interferometry assays."
## [2] " More importantly, the results presented confirm the biosensor performs reliably, with a wide dynamic range and a proportional response at different percentages of full-length RNA, even when gene-sized mRNAs were used."
## [3] " Thus, the features of the proposed biosensor would allow to end-users of products such as mRNA vaccines to test the integrity of the product before its application in a low-cost fashion, enabling a more reliable application of these products. Copyright © 2019 Elsevier B.V."
## [4] " All rights reserved. DOI: 10.1016/j.bios.2019.05.008"
##
## [[64]]
## [1] " CONCLUSIONS: The first mRNA vaccines against H10N8 and H7N9 influenza viruses were well tolerated and elicited robust humoral immune responses. ClinicalTrials.gov NCT03076385 and NCT03345043. Copyright © 2019 The Author(s)."
## [2] " Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.vaccine.2019.04.074"
##
## [[65]]
## [1] " Nanomedicines offer unique opportunities to improve the efficacy of these vaccines."
## [2] " A variety of nanoplatforms have been investigated to deliver molecular or cellular or subcellular vaccines to target lymphoid tissues and cells, thereby promoting the potency and durability of anti-tumor immunity while reducing adverse side effects."
## [3] " In this article, we reviewed the key parameters and features of nanovaccines for cancer immunotherapy; we highlighted recent advances in the development of cancer nanovaccines based on synthetic nanocarriers, biogenic nanocarriers, as well as semi-biogenic nanocarriers; and we summarized newly emerging types of nanovaccines, such as those based on stimulator of interferon genes agonists, cancer neoantigens, mRNA vaccines, as well as artificial antigen-presenting cells."
## [4] " This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease. © 2019 Wiley Periodicals, Inc. DOI: 10.1002/wnan.1559 PMCID: PMC7040494"
##
## [[66]]
## [1] " To evaluate the ability of the DENV1-NS poly-epitope to express the antigenic peptides in the context of different HLA class I molecules, we established its in vivo immunogenicity by measuring, after DNA immunization and electroporation, the activation of DENV-specific CD8 T cells in transgenic mice expressing the human HLA-A*0201, -A*2402, -B*0702, and -B*3502 class I alleles."
## [2] " We then engineered a lipid nanoparticle (LNP) encapsulated modified mRNA vaccine encoding DENV1-NS and tested immunogenicity and protection in these human HLA class I transgenic mice, after transient blockade of the interferon (IFN) type I receptor."
## [3] " Significant protection was observed, after two injections of the mRNA vaccine."
## [4] " Collectively, these data strongly support the development of T cell-based vaccines targeting immunodominant T cell epitopes that generate potent virus-specific T cell responses conferring immunity against DENV infection. DOI: 10.3389/fimmu.2019.01424 PMCID: PMC6598640"
##
## [[67]]
## [1] " Using a three-dimensional multi-component reaction system, we synthesized and evaluated the vaccine potential of over 1,000 lipid formulations."
## [2] " The top candidate formulations induced a robust immune response, and were able to inhibit tumor growth and prolong survival in melanoma and human papillomavirus E7 in vivo tumor models."
## [3] " The top-performing lipids share a common structure: an unsaturated lipid tail, a dihydroimidazole linker and cyclic amine head groups."
## [4] " These formulations induce antigen-presenting cell maturation via the intracellular stimulator of interferon genes (STING) pathway, rather than through Toll-like receptors, and result in limited systemic cytokine expression and enhanced anti-tumor efficacy. DOI: 10.1038/s41587-019-0247-3"
##
## [[68]]
## NULL
##
## [[69]]
## [1] " Focusing on respiratory syncytial virus infection, influenza and tuberculosis, Fauci and Mascola discuss the impact of structure-based vaccine design, gene-based vaccine platforms and advances in adjuvant development. The atomic level structure of the viral surface fusion protein of respiratory syncytial virus provided key insights that enabled the production of a stabilized subunit vaccine candidate that elicited robust immunogenicity in a phase I study."
## [2] " Technical advances in mRNA vaccines have led to improved intracellular stability and antigen expression, leading to robust and durable immune responses. mRNA candidate vaccines encoding full length haemagglutinin from two pandemic influenzas strains were safe and immunogenic in phase I studies."
## [3] " A tuberculosis (TB) subunit recombinant fusion protein (M72) formulated with a potent adjuvant (ASO1E) was effective at preventing activation of pulmonary TB in latently infected adults."
## [4] " Bacillus Calmetteâ\200“GuĂ©rin (BCG) revaccination of uninfected adolescents provided protection against Mycobacterium tuberculosis infection. DOI: 10.1038/s41577-019-0243-3 PMCID: PMC7222935"
##
## [[70]]
## [1] " Findings elucidated in preclinical studies have revealed the importance of the interaction between the cellular and humoral immune system."
## [2] " As a result, several new rationally designed vaccine strategies have been developed and explored in the last 6 years, including native-like envelope trimers, nanoparticle, and mRNA vaccine design strategies among others. Several of these strategies have shown enough promise in animal models to progress toward first-in-human Phase I clinical trials."
## [3] " IMPLICATIONS: Rapid developments in preclinical and early-phase clinical studies suggest that a tolerable and effective HIV vaccine may be on the horizon. Copyright © 2020 Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/j.clinthera.2020.01.009 PMCID: PMC7102617"
##
## [[71]]
## [1] " The stability, immunogenicity, translation efficiency, and delivery are all pivotal issues need to be addressed."
## [2] " In the recently published research results, these issues are gradually being overcome by state-of-the-art development technologies."
## [3] " In this review, we describe the structural properties and modification technologies of mRNA, summarize the latest advances in developing mRNA delivery systems, review the preclinical and clinical applications, and put forward our views on the prospect and challenges of developing mRNA into a new class of drug. Copyright © 2020 Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/j.biotechadv.2020.107534"
##
## [[72]]
## [1] " Many vaccine candidates are under development, including DNA, modified mRNA, protein subunit, killed virus, and attenuated live virus vaccines."
## [2] " Lessons learned from prior vaccine studies and select candidate vaccines are discussed, including a trivalent nucleoside-modified mRNA vaccine that our laboratory is pursuing."
## [3] " We are optimistic that an effective vaccine for prevention of genital herpes will emerge in this decade. Copyright © 2020 Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/j.trsl.2020.03.004 PMCID: PMC7293938"
##
## [[73]]
## [1] " [At least 68 vaccine candidates under development]. [Article in Swedish] Leach S(1). Author information: (1). The development of vaccines against SARS-CoV-2 is progressing at an unparalleled speed."
## [2] " As of the 29th of March, there were at least 68 vaccine candidates comprising several different vaccine designs, including whole killed virus, subunit, attenuated, viral vector, DNA and mRNA vaccines."
## [3] " Whilst it usually takes 10-15 years to develop a vaccine, it has only taken just over 9 weeks from the publication of the viral genetic sequence for the first vaccine candidate to reach clinical testing."
## [4] " Development has been expediated by using existing technological platforms and by performing preclinical and clinical testing simultaneously. "
##
## [[74]]
## [1] " LNPs formulated with C24 alkyl derivatives of cholesterol show a polymorphic shape and various degrees of multilamellarity and lipid partitioning, likely due to phase separation."
## [2] " The addition of methyl and ethyl groups to the C24 alkyl tail of the cholesterol backbone induces multilamellarity (>50% increase compared to cholesterol), while the addition of a double bond induces lipid partitioning (>90% increase compared to cholesterol)."
## [3] " LNPs with multilamellar and faceted structures, as well as a lamellar lipid phase, showed higher gene transfection."
## [4] " Unraveling the structure of mRNA-LNPs can enable their rational design toward enhanced gene delivery. DOI: 10.1021/acs.nanolett.0c01386 PMCID: PMC7228479"
##
## [[75]]
## NULL
##
## [[76]]
## [1] " Cationic liposome/protamine complex (LPC) showed significantly greater efficiency in uptake of vaccine particles in vitro and stronger capacities to stimulate dendritic cell maturation, which further induced a potent anti-tumor immune response."
## [2] " Intranasal immunization of mice with cationic LPC containing mRNA encoding cytokeratin 19 provoked a strong cellular immune response and slowed tumor growth in an aggressive Lewis lung cancer model."
## [3] " The results of this study provide evidence that cationic LPC can be used as a safe and effective adjuvant and this mRNA formulation provides a basis for anti-cancer vaccination of humans. Copyright © 2020 Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/j.cellimm.2020.104143"
##
## [[77]]
## [1] " Ad5-nCoV is based on the replication-defective adenovirus type 5 as the vector to express 2019-nCoV spike protein."
## [2] " The another vaccine is mRNA-1273 developed by the National Institute of Allergy and Infectious Diseases and Moderna, Inc.. RNA-1273 is an mRNA vaccine expressing 2019-nCoV spike protein."
## [3] " Although the rapid development of 2019-nCoV vaccine, it still faces many unknown challenges, including the antigenic characteristics of the 2019-nCoV, the influence of antigenic variation, the protective immune response of host, the protection of the elderly population, and the downstream manufacturing process of the new vaccine."
## [4] " The safety and efficacy of vaccines are the first priority for vaccine development and should be carefully evaluated. Publisher: ć–°ĺž‹ĺ† çŠ¶ç—…ćŻ’ďĽ\2102019-nCoV）感染暴发ćµ\201č\241ŚĺŻąĺ…¨ç\220\203公众ĺ\201Ąĺş·ćž„ć\210\220了严重ĺ¨\201č\203\201，疫苗接种ć\230Żćś‰ć•\210é\242„é\230\262病毒感染ćµ\201č\241Śçš„手段ă\200‚2019-nCoV与ć\200Ąć\200§ĺ‘Ľĺ\220¸ç»Ľĺ\220\210ĺľ\201ĺ† çŠ¶ç—…ćŻ’ďĽ\210SARS-CoV）和ä¸ä¸śĺ‘Ľĺ\220¸ç»Ľĺ\220\210ĺľ\201ĺ† çŠ¶ç—…ćŻ’ďĽ\210MERS-CoV）ĺ\220Śĺ±žäşŽÎ\262-ĺ† çŠ¶ç—…ćŻ’ă\200‚基于对SARS-CoVĺ’ŚMERS-CoV的了解，科ĺ¦ĺ®¶ĺŻą2019-nCoV病毒特ĺľ\201çš„ç ”ç©¶ă\200\201ĺ\200\231é\200‰ćŠ—原及č\241¨ä\275Ťçš„鉴定ă\200\201动物ć¨\241型的建立ă\200\201ĺ…Ťç–«ĺş”ç”çš„ćŁ\200测，疫苗的设č®\241ç‰ĺ·Ąä\275śĺŹ–得了快é\200źčż›ĺ±•ă\200‚ć–°ĺž‹ĺ† çŠ¶ç—…ćŻ’ç–«č‹—ďĽ\210ć–°ĺ† ç–«č‹—ďĽ‰çš„ç ”ĺŹ‘äąźĺŹ–ĺľ—äş†ĺż«é\200źčż›ĺ±•ďĽŚć–°ĺ† ç–«č‹—ç±»ĺž‹ĺ‡ äąŽć¶µç›–äş†ç›®ĺ‰Ťç–«č‹—ç ”ç©¶çš„ć‰\200有ĺ\275\242式，包括ç\201活疫苗ă\200\201重组蛋ç\231\275ç–«č‹—ă\200\201病毒č\275\275ä\275“ç–«č‹—ă\200\201ć ¸é…¸ç–«č‹—ďĽ\210mRNA疫苗与DNA疫苗）ç‰ă\200‚至2020ĺą´3ćś\210，ĺ·\262有2é\241ąć–°ĺ† ç–«č‹—čż›ĺ…Ąäş†â… ćśźä¸´ĺşŠčŻ•éŞŚďĽŚĺ\210†ĺ\210«ä¸şć\210‘ĺ›\275军事医ĺ¦ç§‘ĺ¦é\231\242č\201”ĺ\220\210天津康希诺生物č‚\241ä»\275ĺ…¬ĺŹ¸ç ”ĺŹ‘çš„ĺźşäşŽč…şç—…ćŻ’č\275\275ä\275“çš„é‡Ťç»„ć–°ĺ† ç–«č‹—ĺ’ŚçľŽĺ›\275Moderna公司的mRNA 疫苗，两种疫苗均以2019-nCoVçš„ĺ\210şçŞ\201蛋ç\231\275ä¸şćŠ—ĺŽźéť¶ć ‡ă\200‚ĺ\220Ść—¶ďĽŚć–°ĺ† ç–«č‹—ç ”ĺŹ‘ä»Ťéť\242临çť\200许多未知的挑ć\210\230，如2019-nCoV病毒抗原特ĺľ\201ă\200\201抗原ĺŹ\230异ă\200\201ćśşä\275“的保护ć\200§ĺ…Ťç–«ĺş”ç”特ĺľ\201以及对č\200\201年及基ç\241\200病人群ć\230Żĺ\220¦ĺ…·ćś‰äżťćŠ¤ďĽŚć–°ĺ† 疫苗量产的生产工艺ç‰ć–ąéť\242仍éś\200č¦\201ć›´ĺ¤šçš„ç ”ç©¶ă\200‚ç–«č‹—ç ”ĺŹ‘ĺ…·ćś‰ĺ…¶ĺ›şćś‰č§„ĺľ‹ďĽŚĺś¨ĺŠ ĺż«é\200źĺş¦çš„ĺ\220Ść—¶ďĽŚäżťčŻ\201疫苗的安全ć\200§ă\200\201有ć•\210ć\200§ć\230Żĺż…é\241»çš„前ćŹ\220ă\200‚. DOI: 10.3760/cma.j.cn112150-20200317-00366"
##
## [[78]]
## [1] " Molecular docking simulation between the epitopes and their corresponding MHC molecules was carried out. 13 epitopes, a highly immunogenic adjuvant, elements for proper sub-cellular trafficking, a secretion booster, and appropriate linkers were combined for constructing the vaccine."
## [2] " The vaccine was found to be antigenic, almost neutral at physiological pH, non-toxic, non-allergenic, capable of generating a robust immune response and had a decent worldwide population coverage."
## [3] " Based on these parameters, this design can be considered a promising choice for a vaccine against SARS-CoV-2. Copyright © 2020 Elsevier B.V."
## [4] " All rights reserved. DOI: 10.1016/j.ijbiomac.2020.06.213 PMCID: PMC7319648"
##
## [[79]]
## [1] " CONCLUSIONS: The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified."
## [2] " These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461). Copyright © 2020 Massachusetts Medical Society. DOI: 10.1056/NEJMoa2022483 PMCID: PMC7377258"
##
## [[80]]
## [1] " Nanotechnology benefits modern vaccine design since nanomaterials are ideal for antigen delivery, as adjuvants, and as mimics of viral structures."
## [2] " In fact, the first vaccine candidate launched into clinical trials is an mRNA vaccine delivered via lipid nanoparticles."
## [3] " To eradicate pandemics, present and future, a successful vaccine platform must enable rapid discovery, scalable manufacturing and global distribution."
## [4] " Here, we review current approaches to COVID-19 vaccine development and highlight the role of nanotechnology and advanced manufacturing. DOI: 10.1038/s41565-020-0737-y"
##
## [[81]]
## [1] " Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain."
## [2] " Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1Â week."
## [3] " ARCoV is currently being evaluated in phase 1 clinical trials. Copyright © 2020 Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/j.cell.2020.07.024 PMCID: PMC7377714"
##
## [[82]]
## [1] " Here, we provide a detailed evaluation of the immunogenicity of lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccines encoding the full-length SARS-CoV-2 spike protein or the spike receptor binding domain in mice."
## [2] " We demonstrate that a single dose of these vaccines induces strong type 1 CD4+ and CD8+ TÂ cell responses, as well as long-lived plasma and memory BÂ cell responses."
## [3] " Additionally, we detect robust and sustained neutralizing antibody responses and the antibodies elicited by nucleoside-modified mRNA vaccines do not show antibody-dependent enhancement of infection in vitro."
## [4] " Our findings suggest that the nucleoside-modified mRNA-LNP vaccine platform can induce robust immune responses and is a promising candidate to combat COVID-19. Published by Elsevier Inc. DOI: 10.1016/j.immuni.2020.07.019 PMCID: PMC7392193"
##
## [[83]]
## [1] " Epub 2020 Aug 5. A novel receptor-binding domain (RBD)-based mRNA vaccine against SARS-CoV-2. Tai W(1), Zhang X(1), Drelich A(2), Shi J(1), Hsu JC(2), Luchsinger L(1), Hillyer CD(1), Tseng CK(2), Jiang S(3), Du L(4). Author information: (1)Lindsley F."
## [2] " Kimball Research Institute, New York Blood Center, New York, NY, 10065, USA. (2)Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA. (3)Lindsley F."
## [3] " Kimball Research Institute, New York Blood Center, New York, NY, 10065, USA. sjiang@nybc.org. (4)Lindsley F."
## [4] " Kimball Research Institute, New York Blood Center, New York, NY, 10065, USA. ldu@nybc.org. DOI: 10.1038/s41422-020-0387-5 PMCID: PMC7403570"
##
## [[84]]
## [1] " Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100Â ÎĽg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-ÎĽg dose."
## [2] " RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose."
## [3] " Geometric mean neutralizing titres reached 1.9-4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14Â days after a positive SARS-CoV-2 PCR."
## [4] " These results support further evaluation of this mRNA vaccine candidate. DOI: 10.1038/s41586-020-2639-4"
##
## [[85]]
## NULL
##
## [[86]]
## NULL
##
## [[87]]
## NULL
##
## [[88]]
## NULL
##
## [[89]]
## NULL
##
## [[90]]
## [1] " Through a comprehensive analysis of endogenous gene expression and de novo design of UTRs, the optimal combination of 5' and 3' UTR are identified and termed NASAR, which are 5- to 10-fold more efficient than the tested endogenous UTRs."
## [2] " More importantly, NASAR mRNAs delivered by lipid-derived TT3 nanoparticles trigger a dramatic expression of potential SARS-CoV-2 antigens."
## [3] " The antigen-specific antibodies induced by TT3-nanoparticles and NASAR mRNAs are over two orders of magnitude more than that induced by the FDA-approved lipid nanoparticle material MC3 in vaccinated mice."
## [4] " These NASAR mRNAs merit further development as alternative SARS-CoV-2 vaccines. © 2020 Wiley-VCH GmbH. DOI: 10.1002/adma.202004452"
##
## [[91]]
## NULL
##
## [[92]]
## [1] " Immune sera broadly neutralized pseudoviruses with diverse SARS-CoV-2 spike variants."
## [2] " Most participants had T helper type 1 (TH1)-skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion."
## [3] " Interferon-Îł was produced by a large fraction of RBD-specific CD8+ and CD4+ T cells."
## [4] " The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms. DOI: 10.1038/s41586-020-2814-7"
##
## [[93]]
## [1] " Switching a patient from a reference drug to a biosimilar or from one biosimilar to another (interchangeability) has so far been considered harmless."
## [2] " Since February 2020, there has been a provisional decision in Germany that patients should be switched according to an economic prescription method."
## [3] " Further scientific findings on the interchangeability of biosimilars and experiences with the supply practices of biosimilars should be collected and evaluated.In this article, the current situation regarding marketing authorizations of biosimilars in the European Union is reviewed."
## [4] " The role of clinical trials for biosimilars is presented, and challenges of biosimilar development and views on interchangeability are discussed. DOI: 10.1007/s00103-020-03225-5"
##
## [[94]]
## [1] "10.1016/j.accpm.2020.10.006."
## [2] " Epub 2020 Oct 20. Vaccines against COVID-19. Locht C(1). Author information: (1)Univ."
## [3] " Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR9017 - CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France."
## [4] " Electronic address: camille.locht@pasteur-lille.fr. DOI: 10.1016/j.accpm.2020.10.006 PMCID: PMC7574838"
##
## [[95]]
## [1] " Here, we directly compared two vaccine platforms-mRNA vaccines and a recombinant protein formulated with an MF59-like adjuvant-looking for their abilities to quantitatively and qualitatively shape SARS-CoV-2-specific primary GC responses over time."
## [2] " We demonstrated that a single immunization with SARS-CoV-2 mRNA, but not with the recombinant protein vaccine, elicited potent SARS-CoV-2-specific GC B and T follicular helper (Tfh) cell responses as well as LLPCs and MBCs. Importantly, GC responses strongly correlated with neutralizing antibody production. mRNA vaccines more efficiently induced key regulators of the Tfh cell program and influenced the functional properties of Tfh cells."
## [3] " Overall, this study identifies SARS-CoV-2 mRNA vaccines as strong candidates for promoting robust GC-derived immune responses. Copyright © 2020 Elsevier Inc."
## [4] " All rights reserved. DOI: 10.1016/j.immuni.2020.11.009 PMCID: PMC7680029"
##
## [[96]]
## [1] " MMWR Morb Mortal Wkly Rep. 2020 Dec 18;69(50):1922-1924. doi: 10.15585/mmwr.mm6950e2. The Advisory Committee on Immunization Practices' Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine - United States, December 2020. Oliver SE, Gargano JW, Marin M, Wallace M, Curran KG, Chamberland M, McClung N, Campos-Outcalt D, Morgan RL, Mbaeyi S, Romero JR, Talbot HK, Lee GM, Bell BP, Dooling K. On December 11, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Pfizer-BioNTech COVID-19 (BNT162b2) vaccine (Pfizer, Inc; Philadelphia, Pennsylvania), a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine encoding the prefusion spike glycoprotein of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). Vaccination with the Pfizer-BioNTech COVID-19 vaccine consists of 2 doses (30 ÎĽg, 0.3 mL each) administered intramuscularly, 3 weeks apart."
## [2] " On December 12, 2020, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation* for use of the Pfizer-BioNTech COVID-19 vaccine in persons aged ≥16 years for the prevention of COVID-19."
## [3] " To guide its deliberations regarding the vaccine, ACIP employed the Evidence to Recommendation (EtR) Framework,â\200 using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.§ The recommendation for the Pfizer-BioNTech COVID-19 vaccine should be implemented in conjunction with ACIP's interim recommendation for allocating initial supplies of COVID-19 vaccines (2)."
## [4] " The ACIP recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine under EUA is interim and will be updated as additional information becomes available. DOI: 10.15585/mmwr.mm6950e2 PMCID: PMC7745957"