CVnCoV and CV2CoV protect human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2

Hoffmann, Donata; Corleis, Björn; Rauch, Susanne; Roth, Nicole; Mühe, Janine; Halwe, Nico Joel; Ulrich, Lisa K.; Fricke, Charlie; Schön, Jacob; Kraft, Anna; Breithaupt, Angele; Wernike, Kerstin; Michelitsch, Anna; Sick, Franziska; Wylezich, Claudia; Hoffmann, Bernd; Thran, Moritz; Theß, Andreas; Mueller, Stefan O.; Mettenleiter, Thomas C.; Petsch, Benjamin; Dorhoi, Anca; Beer, Martin

doi:10.1038/s41467-021-24339-7

Cited by 46 publications

(47 citation statements)

References 39 publications

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“…While previous studies in rodents and nonhuman primates have demonstrated protection by CVnCoV 2,23,24 , this was only studied in the lower respiratory tract 24 . In the present study, CVnCoV provided only modest reductions in viral loads in BAL and NS compared with sham controls.…”

Section: Discussionmentioning

confidence: 99%

“…The observed vaccine efficacy against symptomatic COVID-19 was approximately 48% and 53% in the overall study population and in the 18-60 years of age subgroup, respectively 1 . CV2CoV is a second-generation mRNA vaccine that involves modifications of the non-coding regions that were selected based on an empiric screen for improved antigen expression 2,3 . Both CVnCoV and CV2CoV are based on RNActive® technology [4][5][6][7] and consist of non-chemically modified, sequence engineered mRNA without pseudouridine [6][7][8][9][10][11][12] .…”

mentioning

confidence: 99%

“…Both vaccines encode for the same full-length, pre-fusion stabilized SARS-CoV-2 spike (S) 13,14 and are encapsulated in lipid nanoparticles (LNP) with identical composition. CV2CoV has been engineered with different non-coding regions flanking the open reading frame, which have previously been shown to improve transgene expression 3 and protection against SARS-CoV-2 in ACE2 transgenic mice 2 . Specifically, CV2CoV includes 5' UTR HSD17B4 and 3' UTR PSMB3 elements, followed by a histone stem loop motif and a poly-A sequence (Fig.…”

mentioning

confidence: 99%

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Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine

Gebre

Rauch

Roth

et al. 2021

Nature

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107

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The CVnCoV (CureVac) mRNA vaccine for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was recently evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine containing non-modified nucleosides but with optimized non-coding regions and enhanced antigen expression. Here we report the results of a head-to-head comparison of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in non-human primates. We immunized 18 cynomolgus macaques with two doses of 12 μg lipid nanoparticle-formulated CVnCoV or CV2CoV or with sham (n = 6 per group). Compared with CVnCoV, CV2CoV induced substantially higher titres of binding and neutralizing antibodies, memory B cell responses and T cell responses as well as more potent neutralizing antibody responses against SARS-CoV-2 variants, including the Delta variant. Moreover, CV2CoV was found to be comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. Although CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tracts. Binding and neutralizing antibody titres were correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in non-human primates.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine

Gebre

Rauch

Roth

et al. 2021

Nature

Self Cite

107

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“…Together, the combination of multiple transgenic hACE2-expressing mouse models under various promoters, adenovirus-based methods for transduction of multiple mouse strains with hACE2, mouse-adapted SARS-CoV-2 strains, and the susceptibility of mice to emerging VOC has resulted in laboratory mice becoming highly useful models for SARS-CoV-2 infection studies and efficacy testing of vaccines and therapeutics [ 220 , 221 , 222 , 223 , 224 ].…”

Section: Main Textmentioning

confidence: 99%

Natural and Experimental SARS-CoV-2 Infection in Domestic and Wild Animals

Meekins

Gaudreault

Richt

2021

Viruses

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SARS-CoV-2 is the etiological agent responsible for the ongoing COVID-19 pandemic, which continues to spread with devastating effects on global health and socioeconomics. The susceptibility of domestic and wild animal species to infection is a critical facet of SARS-CoV-2 ecology, since reverse zoonotic spillover events resulting in SARS-CoV-2 outbreaks in animal populations could result in the establishment of new virus reservoirs. Adaptive mutations in the virus to new animal species could also complicate ongoing mitigation strategies to combat SARS-CoV-2. In addition, animal species susceptible to SARS-CoV-2 infection are essential as standardized preclinical models for the development and efficacy testing of vaccines and therapeutics. In this review, we summarize the current findings regarding the susceptibility of different domestic and wild animal species to experimental SARS-CoV-2 infection and provide detailed descriptions of the clinical disease and transmissibility in these animals. In addition, we outline the documented natural infections in animals that have occurred at the human–animal interface. A comprehensive understanding of animal susceptibility to SARS-CoV-2 is crucial to inform public health, veterinary, and agricultural systems, and to guide environmental policies.

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“…This candidate is based on the analysis of potential SARS-CoV-2 variants-of-concern in multivalent vaccine formats. Recent preclinical data for CV2CoV show that it induced complete protection against variant B.1.351 in a transgenic mouse model [208].…”

Section: The Main Rna-based Vaccines For Covid-19mentioning

confidence: 99%

The Importance of RNA-Based Vaccines in the Fight against COVID-19: An Overview

et al. 2021

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In recent years, vaccine development using ribonucleic acid (RNA) has become the most promising and studied approach to produce safe and effective new vaccines, not only for prophylaxis but also as a treatment. The use of messenger RNA (mRNA) as an immunogenic has several advantages to vaccine development compared to other platforms, such as lower coast, the absence of cell cultures, and the possibility to combine different targets. During the COVID-19 pandemic, the use of mRNA as a vaccine became more relevant; two out of the four most widely applied vaccines against COVID-19 in the world are based on this platform. However, even though it presents advantages for vaccine application, mRNA technology faces several pivotal challenges to improve mRNA stability, delivery, and the potential to generate the related protein needed to induce a humoral- and T-cell-mediated immune response. The application of mRNA to vaccine development emerged as a powerful tool to fight against cancer and non-infectious and infectious diseases, for example, and represents a relevant research field for future decades. Based on these advantages, this review emphasizes mRNA and self-amplifying RNA (saRNA) for vaccine development, mainly to fight against COVID-19, together with the challenges related to this approach.

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CVnCoV and CV2CoV protect human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2

Cited by 46 publications

References 39 publications

Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine

Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine

Natural and Experimental SARS-CoV-2 Infection in Domestic and Wild Animals

The Importance of RNA-Based Vaccines in the Fight against COVID-19: An Overview

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