Current Status of COVID‐19 (Pre)Clinical Vaccine Development

Ye, Tingting; Zhong, Zifu; Garcı́a-Sastre, Adolfo; Schotsaert, Michael; Geest, Bruno G. De

doi:10.1002/ange.202008319

Cited by 17 publications

(17 citation statements)

References 59 publications

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“…The RNA drug substance production was modelled based on single-use equipment. The bottleneck for drug substance production is the formulation step, whereby the RNA is encapsulated into lipid nanoparticles (LNPs) using a controlled mixing process [ 8 , 35 ]. For this purpose, microfluidic mixing devices are commonly used to mix an aqueous stream containing the RNA with an ethanol stream containing the following four lipid components: phospholipids, polyethylene glycol (PEG) lipids, cholesterol and a proprietary ionisable lipid [ 35 , 36 , 37 , 38 , 39 , 40 ].…”

Section: Resultsmentioning

confidence: 99%

Resources, Production Scales and Time Required for Producing RNA Vaccines for the Global Pandemic Demand

et al. 2020

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To overcome pandemics, such as COVID-19, vaccines are urgently needed at very high volumes. Here we assess the techno-economic feasibility of producing RNA vaccines for the demand associated with a global vaccination campaign. Production process performance is assessed for three messenger RNA (mRNA) and one self-amplifying RNA (saRNA) vaccines, all currently under clinical development, as well as for a hypothetical next-generation saRNA vaccine. The impact of key process design and operation uncertainties on the performance of the production process was assessed. The RNA vaccine drug substance (DS) production rates, volumes and costs are mostly impacted by the RNA amount per vaccine dose and to a lesser extent by the scale and titre in the production process. The resources, production scale and speed required to meet global demand vary substantially in function of the RNA amount per dose. For lower dose saRNA vaccines, global demand can be met using a production process at a scale of below 10 L bioreactor working volume. Consequently, these small-scale processes require a low amount of resources to set up and operate. RNA DS production can be faster than fill-to-finish into multidose vials; hence the latter may constitute a bottleneck.

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Section: Resultsmentioning

confidence: 99%

Resources, Production Scales and Time Required for Producing RNA Vaccines for the Global Pandemic Demand

et al. 2020

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“…The trial was supposed to finish in 3 months. Later in September, phase IIa clinical trials among 150 participants (including placebos) were started to assess the safety and efficacy of GX-19, and the estimated completion date will be March 17, 2021 ( Ye et al, 2020 ).…”

Section: Dna Vaccinementioning

confidence: 99%

Potential of Immune-Related Therapy in COVID-19

Yuan

Liu

et al. 2021

Front. Pharmacol.

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At the beginning of 2020, a sudden outbreak of new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infections led to anxiety, panic, and crisis among people worldwide. The outbreak first occurred in Wuhan, China, in late December 2019 and then spread rapidly across the globe, thus becoming a major public health emergency. Although the current epidemic situation in China tends to be stable, coronavirus disease 2019 (COVID-19) continues to spread globally. At present, no specific therapeutic drugs and vaccines are available against COVID-19. Also, the pathogenesis of the SARS-CoV-2 is not fully clear. Human immunity is important in SARS-CoV-2 infection. Studies have shown that excessive inflammation caused by SARS-CoV-2 infection and subsequent induced uncontrolled cytokine storm are the main causes of disease deterioration and death of severe patients. Therefore, immune-related research is of great significance for the prevention, control, and prognosis of COVID-19. This study aimed to review the latest research on immune-related treatment of COVID-19.

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“…Furthermore, LNPs be can readily modified to target specific subsets of antigen-presenting cells (APCs), which makes them more suitable for vaccine candidates [ 13 , 14 ]. Interestingly, both mRNA1273 and BNT162 have adopted LNP (lipid nanoparticles) as a delivery system of their mRNA payload in clinical trials for the COVID-19 vaccine [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Conjugation of Mannans to Enhance the Potency of Liposome Nanoparticles for the Delivery of RNA Vaccines

et al. 2021

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Recent approval of mRNA vaccines to combat COVID-19 have highlighted the potential of this platform. Lipid nanoparticles (LNP) is the delivery vehicle of choice for mRNA as they prevent its enzymatic degradation by encapsulation. We have recently shown that surface exposition of mannose, incorporated in LNPs as stable cholesterol-amine conjugate, enhances the potency of self-amplifying RNA (SAM) replicon vaccines through augmented uptake by antigen presenting cells (APCs). Here, we generated a new set of LNPs whose surface was modified with mannans of different length (from mono to tetrasaccharide), in order to study the effect on antibody response of model SAM replicon encoding for the respiratory syncytial virus fusion F protein. Furthermore, the impact of the mannosylated liposomal delivery through intradermal as well as intramuscular routes was investigated. The vaccine priming response showed to improve consistently with increase in the chain length of mannoses; however, the booster dose response plateaued above the length of disaccharide. An increase in levels of IgG1 and IgG2a was observed for mannnosylated lipid nanoparticles (MLNPs) as compared to LNPs. This work confirms the potential of mannosylated SAM LNPs for both intramuscular and intradermal delivery, and highlights a disaccharide length as sufficient to ensure improved immunogenicity compared to the un-glycosylated delivery system.

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Current Status of COVID‐19 (Pre)Clinical Vaccine Development

Cited by 17 publications

References 59 publications

Resources, Production Scales and Time Required for Producing RNA Vaccines for the Global Pandemic Demand

Resources, Production Scales and Time Required for Producing RNA Vaccines for the Global Pandemic Demand

Potential of Immune-Related Therapy in COVID-19

Conjugation of Mannans to Enhance the Potency of Liposome Nanoparticles for the Delivery of RNA Vaccines

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