Efficacy and Safety of the CVnCoV SARS-CoV-2 mRNA Vaccine Candidate: Results from Herald, a Phase 2b/3, Randomised, Observer-Blinded, Placebo-Controlled Clinical Trial in Ten Countries in Europe and Latin America

Kremsner, Peter G.; Guerrero, Rodolfo A. Ahuad; Arana, Eunate; Aroca, Gustavo; Bonten, Marc J. M.; Chandler, Reynaldo; Corral, Gonzalo; Block, Eddie Jan Louis De; Ecker, Lucie; Gabor, Julian; Lopez, Carlos; Gonzales, Lucy A. De; González, María Angélica Granados; Gorini, Nestor; Grobusch, Martin P.; Hrabar, Adrian D.; Junker, Helga; Kimura, Alan; Lanata, Claudio F.; Lehmann, Clara; Leroux-Roels, Isabel; Mann, Philipp; Martínez‐Reséndez, Michel F.; Ochoa, Theresa J.; Poy, Carlos; Fentanes, Maria Jose Reyes; Mejia, Luis Maria Rivera; Herrera, Vida Veronica Ruiz; Sáez-Llorens, Xavier; Schönborn‐Kellenberger, Oliver; Schunk, Mirjam; Garcia, Alexandra Sierra; Vergara, Itziar; Verstraeten, Thomas; Vico, Marisa; Oostvogels, Lidia

doi:10.2139/ssrn.3911826

Cited by 28 publications

(29 citation statements)

References 13 publications

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“…Interestingly, there appeared to be significant variability in antibody responses to 12 μg CVnCoV, though the sample size was small. Cure-Vac has started a phase IIb/III randomized placebo-controlled blinded safety and efficacy trial (NCT04652102) with 39,680 participants (vaccine and placebo groups in a 1:1 ratio) in ten countries using two immunizations 28 days apart with the 12 μg dose (13). Primary efficacy analysis included symptomatic COVID-19 more than 14 days after administration of the second dose.…”

Section: Curevac Vaccinementioning

confidence: 99%

mRNA Vaccines in the COVID-19 Pandemic and Beyond

2022

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. This extraordinary situation prompted entities in government, industry, and academia to work together at unprecedented speed to develop safe and effective vaccines. Indeed, vaccines of multiple types have been generated in record time, and many have been evaluated in clinical trials. Of these, messenger RNA (mRNA) vaccines have emerged as lead candidates due to their speed of development and high degree of safety and efficacy. To date, two mRNA vaccines have received approval for human use, providing proof of the feasibility of this next-generation vaccine modality. This review gives a detailed overview about the types of mRNA vaccines developed for SARS-CoV-2, discusses and compares preclinical and clinical data, gives a mechanistic overview about immune responses generated by mRNA vaccination, and speculates on the challenges and promising future of this emergent vaccine platform.

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Section: Curevac Vaccinementioning

confidence: 99%

mRNA Vaccines in the COVID-19 Pandemic and Beyond

2022

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“…In fact, the unmodified COVID-19 mRNA vaccine candidate in late-stage clinical trials (CVnCoV, developed by Curevac) had a maximum dose of 12 µg. However, the recent CVnCoV vaccine clinical trial results showed only 48% of efficacy against any severity of the disease, ( Kremsner et al, 2021 ).…”

Section: Modified Vs Unmodified Covid-19 Mrna Vaccines Lead To Different Outcomesmentioning

confidence: 99%

“…In contrast, another COVID-19 mRNA vaccine candidate (developed by Curevac NV), which is based on an unmodified (Ψ-lacking) mRNA encoding the same COVID-19 spike protein and uses the same LNPs as the Pfizer-BioNTech vaccine does ( Buschmann et al, 2021 ), failed to meet expectations ( Baker and Dolgin, 2021 ). The clinical trial test results ultimately revealed only 48% of efficacy against symptomatic disease ( Kremsner et al, 2021 ) for the unmodified mRNA vaccine, suggesting that modified Ψ and use of LNP technology were both critical success factors for platform validation of mRNA ( Dolgin, 2021a ). In this mini-review, we will emphasize the main features of this RNA modification and a chemically evolved version of it that contribute to the success of COVID-19 mRNA vaccines and the control of the pandemic.…”

Section: Introductionmentioning

confidence: 99%

The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines

Morais

Adachi

2021

Front. Cell Dev. Biol.

138

112

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The current COVID-19 pandemic is a massive source of global disruption, having led so far to two hundred and fifty million COVID-19 cases and almost five million deaths worldwide. It was recognized in the beginning that only an effective vaccine could lead to a way out of the pandemic, and therefore the race for the COVID-19 vaccine started immediately, boosted by the availability of the viral sequence data. Two novel vaccine platforms, based on mRNA technology, were developed in 2020 by Pfizer-BioNTech and Moderna Therapeutics (comirnaty® and spikevax®, respectively), and were the first ones presenting efficacies higher than 90%. Both consisted of N1-methyl-pseudouridine-modified mRNA encoding the SARS-COVID-19 Spike protein and were delivered with a lipid nanoparticle (LNP) formulation. Because the delivery problem of ribonucleic acids had been known for decades, the success of LNPs was quickly hailed by many as the unsung hero of COVID-19 mRNA vaccines. However, the clinical trial efficacy results of the Curevac mRNA vaccine (CVnCoV) suggested that the delivery system was not the only key to the success. CVnCoV consisted of an unmodified mRNA (encoding the same spike protein as Moderna and Pfizer-BioNTech’s mRNA vaccines) and was formulated with the same LNP as Pfizer-BioNTech’s vaccine (Acuitas ALC-0315). However, its efficacy was only 48%. This striking difference in efficacy could be attributed to the presence of a critical RNA modification (N1-methyl-pseudouridine) in the Pfizer-BioNTech and Moderna’s mRNA vaccines (but not in CVnCoV). Here we highlight the features of N1-methyl-pseudouridine and its contributions to mRNA vaccines.

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“…However, clinical data were not as good as expected. Results of their 40,000-participant clinical trial (NCT04652102) unexpectedly resulted in only 47% efficacy, as opposed to over 90% efficacy reported by the approved vaccines [136]. Several hypotheses have been described, such as the presence of new SARS-CoV-2 variants in the countries in which the study was held.…”

Section: Additional Covid-19 Vaccines Based On Mrna and Delivery Vehi...mentioning

confidence: 99%

The Potential of Nanomedicine to Unlock the Limitless Applications of mRNA

Taina-González

Fuente

2022

Pharmaceutics

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The year 2020 was a turning point in the way society perceives science. Messenger RNA (mRNA) technology finally showed and shared its potential, starting a new era in medicine. However, there is no doubt that commercialization of these vaccines would not have been possible without nanotechnology, which has finally answered the long-term question of how to deliver mRNA in vivo. The aim of this review is to showcase the importance of this scientific milestone for the development of additional mRNA therapeutics. Firstly, we provide a full description of the marketed vaccine formulations and disclose LNPs’ pharmaceutical properties, including composition, structure, and manufacturing considerations Additionally, we review different types of lipid-based delivery technologies currently in preclinical and clinical development, namely lipoplexes and cationic nanoemulsions. Finally, we highlight the most promising clinical applications of mRNA in different fields such as vaccinology, immuno-oncology, gene therapy for rare genetic diseases and gene editing using CRISPR Cas9.

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Efficacy and Safety of the CVnCoV SARS-CoV-2 mRNA Vaccine Candidate: Results from Herald, a Phase 2b/3, Randomised, Observer-Blinded, Placebo-Controlled Clinical Trial in Ten Countries in Europe and Latin America

Cited by 28 publications

References 13 publications

mRNA Vaccines in the COVID-19 Pandemic and Beyond

mRNA Vaccines in the COVID-19 Pandemic and Beyond

The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines

The Potential of Nanomedicine to Unlock the Limitless Applications of mRNA

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