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  1. Article ; Online: Nonreplicating synthetic mRNA vaccines: A journey through the European (Journal of Immunology) history.

    Pascolo, Steve

    European journal of immunology

    2023  Volume 53, Issue 7, Page(s) e2249941

    Abstract: The first worldwide article reporting that injections of synthetic nonreplicating mRNA could be used as a vaccine, which originated from a French team located in Paris, was published in the European Journal of Immunology (EJI) in 1993. It relied on work ... ...

    Abstract The first worldwide article reporting that injections of synthetic nonreplicating mRNA could be used as a vaccine, which originated from a French team located in Paris, was published in the European Journal of Immunology (EJI) in 1993. It relied on work conducted by several research groups in a handful of countries since the 1960s, which put forward the precise description of eukaryotic mRNA and the method to reproduce this molecule in vitro as well as how to transfect it into mammalian cells. Thereafter, the first industrial development of this technology began in Germany in 2000, with the founding of CureVac, which stemmed from another description of a synthetic mRNA vaccine published in EJI in 2000. The first clinical studies investigating mRNA vaccines in humans were performed as collaboration between CureVac and the University of Tübingen in Germany as early as 2003. Finally, the first worldwide approved mRNA vaccine (an anti-COVID-19 vaccine) is based on the mRNA technologies developed by BioNTech since its 2008 foundation in Mainz, Germany, and earlier by the pioneering academic work of its founders. In addition to the past, present, and future of mRNA-based vaccines, the article aims to present the geographical distribution of the early work, how the development of the technology was implemented by several independent and internationally distributed research teams, as well as the controversies on the optimal way to design or formulate and administer mRNA vaccines.
    MeSH term(s) Humans ; Animals ; Vaccines, Synthetic ; COVID-19 Vaccines/genetics ; Germany ; Pancreas ; Paris ; RNA, Messenger/genetics ; Mammals
    Chemical Substances Vaccines, Synthetic ; COVID-19 Vaccines ; RNA, Messenger
    Language English
    Publishing date 2023-04-24
    Publishing country Germany
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.202249941
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Synthetic Messenger RNA-Based Vaccines: from Scorn to Hype.

    Pascolo, Steve

    Viruses

    2021  Volume 13, Issue 2

    Abstract: In the race for a vaccine against SARS-CoV-2, the synthetic mRNA format has been shown to be the fastest one and proved to be safe and highly efficient, even at the very low dose of a few µg per injection. The mRNA vaccines are not new: vaccines that are ...

    Abstract In the race for a vaccine against SARS-CoV-2, the synthetic mRNA format has been shown to be the fastest one and proved to be safe and highly efficient, even at the very low dose of a few µg per injection. The mRNA vaccines are not new: vaccines that are based on attenuated mRNA viruses, such as Mumps, Measles, and Rubella, immunize by delivering their mRNAs into the cells of the vaccinated individual, who produces the viral proteins that then prime the immune response. Synthetic mRNA in liposomes can be seen as a modern, more refined, and thereby a safer version of those live attenuated RNA viruses. The anti-COVID-19 mRNA vaccine (coding the SARS-CoV-2 spike protein) is the third synthetic RNA therapeutic being approved. It follows the aptamer Macugen
    MeSH term(s) Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/administration & dosage ; COVID-19 Vaccines/adverse effects ; COVID-19 Vaccines/genetics ; COVID-19 Vaccines/immunology ; Humans ; Pandemics ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; Vaccines, Synthetic/administration & dosage ; Vaccines, Synthetic/adverse effects ; Vaccines, Synthetic/genetics ; Vaccines, Synthetic/immunology ; mRNA Vaccines
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; Vaccines, Synthetic ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-02-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13020270
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Vaccines against COVID-19: Priority to mRNA-Based Formulations.

    Pascolo, Steve

    Cells

    2021  Volume 10, Issue 10

    Abstract: As of September 2021, twenty-one anti-COVID-19 vaccines have been approved in the world. Their utilization will expedite an end to the current pandemic. Besides the usual vaccine formats that include inactivated viruses (eight approved vaccines) and ... ...

    Abstract As of September 2021, twenty-one anti-COVID-19 vaccines have been approved in the world. Their utilization will expedite an end to the current pandemic. Besides the usual vaccine formats that include inactivated viruses (eight approved vaccines) and protein-based vaccines (four approved vaccines), three new formats have been validated: recombinant adenovirus (six approved vaccines), DNA (one approved vaccine), and messenger RNA (mRNA, two approved vaccines). The latter was the fastest (authorized in 2020 in the EU, the USA, and Switzerland). Most Western countries have reserved or use the protein vaccines, the adenovirus vaccines, and mRNA vaccines. I describe here the different vaccine formats in the context of COVID-19, detail the three formats that are chiefly reserved or used in Europe, Canada, and the USA, and discuss why the mRNA vaccines appear to be the superior format.
    MeSH term(s) Adenoviridae/genetics ; Animals ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; Canada ; DNA/genetics ; Drug Approval ; Europe ; Humans ; Mice ; Patient Safety ; RNA, Messenger ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/genetics ; United States
    Chemical Substances COVID-19 Vaccines ; RNA, Messenger ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; DNA (9007-49-2)
    Language English
    Publishing date 2021-10-11
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10102716
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Rplique

    Pascolo, Steve

    Bulletin des Médecins Suisses ; ISSN 1424-4012

    Genetische Impfstoffe gegen COVID-19: Hoffnung oder Risiko

    2020  

    Keywords covid19
    Language French
    Publisher EMH Swiss Medical Publishers, Ltd.
    Publishing country ch
    Document type Article ; Online
    DOI 10.4414/bms.2020.19150
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Sichere und effiziente mRNA-Impfstoffe gegen SARS-CoV-2

    Pascolo, Steve

    Bulletin des Médecins Suisses ; ISSN 1424-4012

    2020  

    Keywords covid19
    Language French
    Publisher EMH Swiss Medical Publishers, Ltd.
    Publishing country ch
    Document type Article ; Online
    DOI 10.4414/bms.2020.19135
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Sichere und effiziente mRNA-Impfstoffe gegen SARS-CoV-2

    Pascolo, Steve

    Schweizerische Ärztezeitung ; ISSN 0036-7486 1424-4004

    2020  

    Keywords covid19
    Language German
    Publisher EMH Swiss Medical Publishers, Ltd.
    Publishing country ch
    Document type Article ; Online
    DOI 10.4414/saez.2020.19135
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Replik auf

    Pascolo, Steve

    Schweizerische Ärztezeitung ; ISSN 0036-7486 1424-4004

    Genetische Impfstoffe gegen COVID-19: Hoffnung oder Risiko

    2020  

    Keywords covid19
    Language German
    Publisher EMH Swiss Medical Publishers, Ltd.
    Publishing country ch
    Document type Article ; Online
    DOI 10.4414/saez.2020.19150
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Time to use a dose of Chloroquine as an adjuvant to anti-cancer chemotherapies.

    Pascolo, Steve

    European journal of pharmacology

    2016  Volume 771, Page(s) 139–144

    Abstract: Chloroquine, a drug used for over 80 years to treat and prevent malaria and, more recently, to treat autoimmune diseases, is very safe but has a plethora of dose-dependent effects. By increasing pH in acidic compartments it inhibits for example lysosomal ...

    Abstract Chloroquine, a drug used for over 80 years to treat and prevent malaria and, more recently, to treat autoimmune diseases, is very safe but has a plethora of dose-dependent effects. By increasing pH in acidic compartments it inhibits for example lysosomal enzymes. In the context of cancer, Chloroquine was found to have direct effects on different types of malignancies that could potentiate chemotherapies. For example, the anti-malaria drug may inhibit both the multidrug-resistance pump and autophagy (mechanisms that tumor cells may use to resist chemotherapies), intercalate in DNA and enhance the penetration of chemotherapeutic drugs in cells or solid cancer tissues. However, these activities were mostly demonstrated at high doses of Chloroquine (higher than 10mg/kg or 10mg/l i.e. ca. 31μM). Nevertheless, it was reported that daily uptake of clinically acceptable doses (less than 10mg/kg) of Chloroquine in addition to chemo-radio-therapy increases the survival of glioblastoma patients (Sotelo et al., 2006; Briceno et al., 2007). However, the optimal dose and schedule of this multi-active drug with respect to chemotherapy has never been experimentally determined. The present article reviews the several known direct and indirect effects of different doses of Chloroquine on cancer and how those effects may indicate that a fine tuning of the dose/schedule of Chloroquine administration versus chemotherapy may be critical to obtain an adjuvant effect of Chloroquine in anti-cancer treatments. We anticipate that the appropriate (time and dose) addition of Chloroquine to the standard of care may greatly and safely potentiate current anti-cancer treatments.
    MeSH term(s) Animals ; Antineoplastic Agents, Phytogenic/pharmacology ; Antineoplastic Agents, Phytogenic/therapeutic use ; Cell Line, Tumor ; Chloroquine/pharmacology ; Chloroquine/therapeutic use ; Humans ; Neoplasms/drug therapy ; Neoplastic Stem Cells/drug effects
    Chemical Substances Antineoplastic Agents, Phytogenic ; Chloroquine (886U3H6UFF)
    Language English
    Publishing date 2016-01-15
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80121-5
    ISSN 1879-0712 ; 0014-2999
    ISSN (online) 1879-0712
    ISSN 0014-2999
    DOI 10.1016/j.ejphar.2015.12.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The messenger's great message for vaccination.

    Pascolo, Steve

    Expert review of vaccines

    2015  Volume 14, Issue 2, Page(s) 153–156

    Abstract: Poly ribonucleic acid (RNA) is the only polymer capable to recapitulate all processes of life: containment of genetic information, enzymatic activities and capacity to create defined 3D structures. Since it has a remarkable chemical stability (at neutral ...

    Abstract Poly ribonucleic acid (RNA) is the only polymer capable to recapitulate all processes of life: containment of genetic information, enzymatic activities and capacity to create defined 3D structures. Since it has a remarkable chemical stability (at neutral or acidic pH) and can be modified to enhance/reduce particular features (e.g., stability in biological RNase containing milieus or recognition by immune sensors), it is a particularly versatile and ideal active pharmaceutical ingredient. However, the utilization of RNA as a gene vehicle (messenger RNA, mRNA) for therapy has only recently been exploited. Within this scope, mRNA-based vaccines designed to trigger anti-cancer, anti-virus or anti-allergy immune responses have been developed. Modifications of mRNA vectors and implementation of adequate formulations have allowed to turn this natural superlative biological molecule into a safe active pharmaceutical ingredient that can virtually address any medical need including vaccination or immunotherapy. This is the newest great message delivered by this messenger.
    MeSH term(s) Cancer Vaccines/immunology ; Genetic Therapy ; Genetic Vectors ; Humans ; Immunotherapy ; Neoplasms/immunology ; Neoplasms/prevention & control ; RNA, Messenger/immunology ; Vaccination ; Vaccines, DNA/immunology
    Chemical Substances Cancer Vaccines ; RNA, Messenger ; Vaccines, DNA
    Language English
    Publishing date 2015-02
    Publishing country England
    Document type Editorial
    ZDB-ID 2181284-6
    ISSN 1744-8395 ; 1476-0584
    ISSN (online) 1744-8395
    ISSN 1476-0584
    DOI 10.1586/14760584.2015.1000871
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: mRNA Vaccines Against Infectious Diseases and Cancer

    Alexander Meisel / Steve Pascolo

    healthbook TIMES. Oncology Hematology, Vol 3, Iss

    2021  Volume 9

    Abstract: Synthetic mRNA acts as a template for synthesizing proteins, protein fragments, or peptides and now has many pharmaceutical applications.^1,2^ Coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS- ...

    Abstract Synthetic mRNA acts as a template for synthesizing proteins, protein fragments, or peptides and now has many pharmaceutical applications.^1,2^ Coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel zoonotic RNA virus, has resulted in the rapid development of dedicated mRNA vaccines.^3–5^ This rapid response was made possible by using mRNA platforms that already existed for experimental vaccines against other infectious diseases and cancer.^6–12^ Carrier-based mRNA vaccines have been developed using lipid-based delivery, peptide-based delivery, polymer-based delivery, and cationic nano-emulsions, as well as dendritic cells.^13^ The mRNA vaccine leads to the expression of encoded antigens in antigen-presenting cells (APCs), generating both innate and adaptive immune responses. Future developments in mRNA therapy in oncology are expected to include adaptations in the routes of administration and co-delivery of multiple mRNAs with other anti-cancer treatments, such as immune checkpoint inhibitors (ICI), radiotherapy, or chemotherapy. In addition, advances in next-generation sequencing (NGS) technology allow the genome, exome, and transcriptome of a single cancer patient to be deciphered. This new knowledge about the diversity of epitopes in different tumors and corresponding specific T cells has allowed the advancement of personalized cancer treatments.^14^ The article aims to present the rationale for the new therapeutic roles of mRNA vaccines, from COVID-19 and other infections to personalized oncology therapeutics.
    Keywords Medicine ; R
    Subject code 610
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher THE HEALTHBOOK COMPANY LTD.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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