Principles for designing an optimal mRNA lipid nanoparticle vaccine

Kon, Edo; Elia, Uri; Peer, Dan

doi:10.1016/j.copbio.2021.09.016

Cited by 125 publications

(89 citation statements)

References 44 publications

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“…Despite an inferior neutralizing antibody response when compared to the homologous BNT162b2, one dose of the CoronaVac vaccine could maintain the immune response induced by the primer dose of BNT162b2 in the Combo group. Studies on the mRNA vaccines have demonstrated their high clinical effectiveness and are adopted widely throughout the world [24,25]. However, the shortage of mRNA COVID-19 vaccines in some countries resulted in the delay of the second dose [26].…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of a Heterologous Prime-Boost COVID-19 Vaccination with mRNA and Inactivated Virus Vaccines Compared with Homologous Vaccination Strategy against SARS-CoV-2 Variants

et al. 2022

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The emergence of SARS-CoV-2 variants may impact the effectiveness of vaccines, while heterologous vaccine strategy is considered to provide better protection. The immunogenicity of an mRNA-inactivated virus vaccine against the SARS-CoV-2 wild-type (WT) and variants was evaluated in the study. SARS-CoV-2 naïve adults (n = 123) were recruited and placed in the following groups: BNT162b2, CoronaVac or BNT162b2-CoronaVac (Combo) Group. Blood samples were collected to measure neutralization antibodies (NAb) by a live virus microneutralization assay (vMN) and surrogate NAb test. The day 56 vMN geometric mean titre (GMT) was 26.2 [95% confident interval (CI), [22.3–30.9] for Combo, 136.9 (95% CI, 104.2–179.7) for BNT162b2, and 14.7 (95% CI, 11.6–18.6) for CoronaVac groups. At 6 months post-first dose, the GMT declined to 8.0, 28.8 and 7.1 in the Combo, BNT162b2 and CoronaVac groups, respectively. Three groups showed reduced neutralizing activity against D614G, beta, theta and delta variants. At day 56 GMT (74.6) and month 6 GMT (22.7), the delta variant in the BNT162b2 group was higher than that in the Combo (day 56, 7.4; month 6, 5.5) and CoronaVac groups (day 56, 8.0; month 6, 5) (p < 0.0001). Furthermore, the mean surrogate NAb value on day 56 in the BNT162b2 group was 594.7 AU/mL and higher than 40.5 AU/mL in Combo and 38.8 AU/mL in CoronaVac groups (p < 0.0001). None of the participants developed severe adverse events, and all other adverse events were self-limiting. The Combo vaccination strategy was safe. The overall vaccine immunogenicity at day 56 and 6 months were comparable to the homologous CoronaVac group but inferior to the homologous BNT162b2 group, against both the WT and all variants. Furthermore, the antibody response of vaccines waned at 6 months and thereby, a third dose of the vaccine is needed for these vaccines.

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Section: Discussionmentioning

confidence: 99%

Immunogenicity of a Heterologous Prime-Boost COVID-19 Vaccination with mRNA and Inactivated Virus Vaccines Compared with Homologous Vaccination Strategy against SARS-CoV-2 Variants

et al. 2022

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“…Increased concentrations of protectants, namely 10% sucrose, is being used in BNT162b and mRNA-1273 products to retain product viability at the more “cold-chain friendly” temperatures that they are preserved into [ 245 ]. Lyophilisation is also a viable, albeit more expensive procedure, that can yield a completely anhydrous product in powder form with extended self-life [ 249 ]. Lyoprotectants utilized can be the same as the cryoprotectants mentioned above as well as substances such as γ-cyclodextrin and hyaluronic acid [ 250 ].…”

Section: Storage Considerationsmentioning

confidence: 99%

mRNA Therapeutic Modalities Design, Formulation and Manufacturing under Pharma 4.0 Principles

et al. 2021

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In the quest for a formidable weapon against the SARS-CoV-2 pandemic, mRNA therapeutics have stolen the spotlight. mRNA vaccines are a prime example of the benefits of mRNA approaches towards a broad array of clinical entities and druggable targets. Amongst these benefits is the rapid cycle “from design to production” of an mRNA product compared to their peptide counterparts, the mutability of the production line should another target be chosen, the side-stepping of safety issues posed by DNA therapeutics being permanently integrated into the transfected cell’s genome and the controlled precision over the translated peptides. Furthermore, mRNA applications are versatile: apart from vaccines it can be used as a replacement therapy, even to create chimeric antigen receptor T-cells or reprogram somatic cells. Still, the sudden global demand for mRNA has highlighted the shortcomings in its industrial production as well as its formulation, efficacy and applicability. Continuous, smart mRNA manufacturing 4.0 technologies have been recently proposed to address such challenges. In this work, we examine the lab and upscaled production of mRNA therapeutics, the mRNA modifications proposed that increase its efficacy and lower its immunogenicity, the vectors available for delivery and the stability considerations concerning long-term storage.

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“…LNPs were nanostructures with 70 to 100 nm in diameter and similar to those used for formulating small interference RNA [ 103 ]. The principles for designing an optimal mRNA lipid nanoparticle vaccine and major types of LNPs were recently reviewed [ 104 , 105 ]. Recently, the need for an additional improvement in m-RNA vaccines was pointed out: the optimization of the vaccines’ stability at low temperature [ 106 ].…”

Section: Vesicles Liposomes Lipid Nanoparticles Disks and Niosomesmentioning

confidence: 99%

Supramolecular Nanostructures for Vaccines

Carmona-Ribeiro

2021

Biomimetics

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Although this is an era of pandemics and many devastating diseases, this is also a time when bionanotechnology flourishes, illuminating a multidisciplinary field where vaccines are quickly becoming a balsam and a prevention against insidious plagues. In this work, we tried to gain and also give a deeper understanding on nanovaccines and their way of acting to prevent or cure cancer, infectious diseases, and diseases caused by parasites. Major nanoadjuvants and nanovaccines are temptatively exemplified trying to contextualize our own work and its relative importance to the field. The main properties for novel adjuvants seem to be the nanosize, the cationic character, and the biocompatibility, even if it is achieved in a low dose-dependent manner.

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Principles for designing an optimal mRNA lipid nanoparticle vaccine

Cited by 125 publications

References 44 publications

Immunogenicity of a Heterologous Prime-Boost COVID-19 Vaccination with mRNA and Inactivated Virus Vaccines Compared with Homologous Vaccination Strategy against SARS-CoV-2 Variants

Immunogenicity of a Heterologous Prime-Boost COVID-19 Vaccination with mRNA and Inactivated Virus Vaccines Compared with Homologous Vaccination Strategy against SARS-CoV-2 Variants

mRNA Therapeutic Modalities Design, Formulation and Manufacturing under Pharma 4.0 Principles

Supramolecular Nanostructures for Vaccines

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