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      Malaria-Antigene in der Ära der mRNA-Impfstoffe : Mögliche Rettungen vor einer der relevantesten und gefährlichsten Kinderkrankheiten des Globalen Südens Translated title: Malarial antigens in the era of mRNA vaccines : Possible salvations from one of the most relevant and dangerous childhood diseases in the global south

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          Abstract

          Bereits in den frühen 1990er-Jahren wurde erstmals eine durch einen mRNA-Impfstoff ausgelöste Immunantwort beschrieben. Seitdem wurden mRNA-Impfstoffe für eine mögliche Prophylaxe erforscht und diskutiert. Doch erst mit der COVID-19-Pandemie erlebten diese Impfstoffe einen wahren Boom. Die ersten mRNA-Impfstoffe wurden gegen SARS-CoV‑2 zugelassen und zeigten große Erfolge. Es ist daher nicht verwunderlich, dass sich die Hersteller auch auf andere Krankheiten und Pathogene konzentrieren. Neben viralen Krankheiten wie Influenza oder Aids steht Malaria weit oben auf dieser Liste. Viele Pharmaunternehmen (u. a. die deutschen Unternehmen BioNTech und CureVac) haben bereits bestätigt, an mRNA-Impfstoffen gegen Malaria zu forschen. Dabei ist die Entwicklung eines funktionierenden Impfstoffes gegen Malaria kein leichtes Unterfangen. Seit den 1960ern wird an möglichen Impfstoffen geforscht. Die Ergebnisse sind dabei eher ernüchternd. Erst 2015 erhielt der Impfstoff RTS,S/AS01 eine positive Bewertung der Europäischen Arzneimittel-Agentur. Seitdem wird der Impfstoff in Afrika getestet.

          Translated abstract

          Even in the early 1990s, an immune response triggered by an mRNA vaccine was described for the first time. Since then, mRNA vaccines have been researched and discussed for possible prophylaxis; however, it was not until the COVID-19 pandemic that these vaccines experienced a real boom. The first mRNA vaccines were licensed against SARS-CoV‑2 and showed great success. It is therefore not surprising that manufacturers are also focusing on other diseases and pathogens. Besides viral diseases, such as influenza and AIDS, malaria is high on this list. Many pharmaceutical companies (including the German companies BioNTech and CureVac) have already confirmed that they are researching mRNA vaccines against malaria. Yet developing a working vaccine against malaria is no easy feat. Research on possible vaccines has been going on since the 1960s. The results have been rather sobering. It was not until 2015 that the vaccine RTS,S/AS01 received a positive evaluation from the European Medicines Agency. Since then, the vaccine has been tested in Africa.

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          Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

          Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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            Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

            Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)
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              Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis

              Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.
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                Author and article information

                Contributors
                yannick.borkens@my.jcu.edu.au
                Journal
                Monatsschr Kinderheilkd
                Monatsschr Kinderheilkd
                Monatsschrift Kinderheilkunde
                Springer Medizin (Heidelberg )
                0026-9298
                1433-0474
                14 July 2022
                14 July 2022
                : 1-10
                Affiliations
                GRID grid.1011.1, ISNI 0000 0004 0474 1797, College of Public Health, Medical and Veterinary Science, , James Cook University, ; 1 James Cook Drive, 4811 Townsville, Queensland Australien
                Author notes
                [Redaktion]

                Florian Lagler, Salzburg

                Antje Neubert, Erlangen

                Wolfgang Rascher, Erlangen

                Author information
                http://orcid.org/0000-0001-9368-6985
                Article
                1554
                10.1007/s00112-022-01554-0
                9281189
                e81cf7c3-5ce9-4f12-82c1-0520e250690f
                © The Author(s) 2022

                Open Access Dieser Artikel wird unter der Creative Commons Namensnennung 4.0 International Lizenz veröffentlicht, welche die Nutzung, Vervielfältigung, Bearbeitung, Verbreitung und Wiedergabe in jeglichem Medium und Format erlaubt, sofern Sie den/die ursprünglichen Autor(en) und die Quelle ordnungsgemäß nennen, einen Link zur Creative Commons Lizenz beifügen und angeben, ob Änderungen vorgenommen wurden.

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                History
                : 13 December 2021
                : 25 April 2022
                Funding
                Funded by: James Cook University
                Categories
                Arzneimitteltherapie

                malaria,mrna-impfstoffe,parasitische infektionskrankheiten,plasmodium,tropenmedizin,mrna vaccines,parasitic infectious diseases,tropical medicine

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