Nanomaterial Delivery Systems for mRNA Vaccines

The dawn of mRNA vaccines: The COVID-19 case.

SARS-CoV-2 mRNA Vaccines: Immunological Mechanism and Beyond.

Accelerated COVID-19 vaccine development: milestones, lessons, and prospects.

Novel approaches for vaccine development.

mRNA technologies have recently proven clinical efficacy against coronavirus disease 2019 and are among the most promising technologies to address the current pandemic. Here, we show preclinical data for our clinical candidate CVnCoV, a lipid nanoparticle-encapsulated mRNA vaccine that encodes full-length, pre-fusion stabilised severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein. In contrast to previously published approaches, CVnCoV is exclusively composed of naturally occurring nucleotides. Immunisation with CVnCoV induced strong humoral responses with high titres of virus-neutralising antibodies and robust T-cell responses. CVnCoV vaccination protected hamsters from challenge with wild-type SARS-CoV-2, demonstrated by the absence of viral replication in the lungs. Hamsters vaccinated with a suboptimal dose of CVnCoV leading to breakthrough viral replication exhibited no evidence of vaccine-enhanced disease. Overall, data presented here provide evidence that CVnCoV represents a potent and safe vaccine candidate against SARS-CoV-2.

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mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents.

The devastating SARS-CoV-2 pandemic demands rapid vaccine development and large scale production to meet worldwide needs. mRNA vaccines have emerged as one of the most promising technologies to address this unprecedented challenge. Here, we show preclinical data for our clinical candidate CVnCoV, a lipid nanoparticle (LNP) encapsulated non-modified mRNA vaccine that encodes the full length, pre-fusion stabilised SARS-CoV-2 Spike (S) protein. S translated from CVnCoV is cleaved, post-translationally modified, and presented on the cell surface, highlighting the ability of mRNA vaccines to mimic antigen presentation during viral infection. Immunisation with CVnCoV induced strong humoral responses with high titres of virus neutralizing antibodies in mice and hamsters and robust CD4+ and CD8+ T cell responses in mice. Most importantly, vaccination with CVnCoV fully protected hamster lungs from challenge with wild type SARS-CoV-2. To gain insights in the risk of vaccine-enhanced disease, hamsters vaccinated with a suboptimal dose of CVnCoV leading to breakthrough viral replication were analysed for signs of vaccine-enhanced disease. No evidence of increased viral replication or exacerbated inflammation and damage to viral target organs was detectable, giving strong evidence for a favourable safety profile of CVnCoV. Overall, data presented here provide evidence that CVnCoV represents a potent and safe vaccine candidate against SARS-CoV-2.

https://biorxiv.org/content/10.1101/2020.10.23.351775v1.full.pdf

mRNA based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus neutralizing antibodies and mediates protection in rodents

The invention relates to mRNA comprising lipid nanoparticles and their medical uses. The lipid nanoparticles of the present invention comprise a cationic lipid according to formula (I), (II) or (III) and/or a PEG lipid according to formula (IV), as well as an mRNA compound comprising an mRNA sequence encoding an antigenic peptide or protein. The invention further relates to the use of said lipid nanoparticles as vaccines or medicaments, in particular with respect to influenza or rabies vaccination.

Lipid nanoparticle mrna vaccines

The present invention is directed to a coding RNA for a Malaria vaccine The coding RNA comprises at least one heterologous untranslated region (UTR), preferably a 3'-UTR and/or a 5'-UTR, and a coding region encoding at least one antigenic peptide or protein derived from a Malaria parasite, in particular at least one antigenic protein derived from circumsporozoite protein (CSP) of a Malaria parasite (eg Plasmodium falciparum) The present invention is also directed to compositions and vaccines comprising said coding RNA in association with a polymeric carrier, a polycationic protein or peptide, or a lipid nanoparticle (LNP) Further, the invention concerns a kit, particularly a kit of parts comprising the coding RNA, or the composition, or the vaccine The invention is also directed to a method of treating or preventing Malaria, and the first and second medical uses of the coding RNA, the composition, the vaccine, and the kit

Kim Ellen Schwendt

Papers

mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents.

mRNA based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus neutralizing antibodies and mediates protection in rodents

Lipid nanoparticle mrna vaccines

Rna for malaria vaccines