Optimization of storage conditions for lipid nanoparticle-formulated self-replicating RNA vaccines.

The recent clinical success of multiple mRNA-based SARS-CoV-2 vaccines has proven the potential of RNA formulated in lipid nanoparticles (LNPs) in humans, and products based on base-modified RNA, sequence-optimized RNA, and self-replicating RNAs formulated in LNPs are all in various stages of clinical development. However, much remains to be learned about critical parameters governing the manufacturing and use of LNP-RNA formulations. One important issue that has received limited attention in the literature to date is the identification of optimal storage conditions for LNP-RNA that preserve long-term activity of the formulations. Here, we analyzed the physical structure, in vivo expression characteristics, and functional activity of alphavirus-derived self-replicating RNA (repRNA)-loaded LNPs encoding HIV vaccine antigens following storage in varying temperatures, buffers, and in the presence or absence of cryoprotectants. We found that for lipid nanoparticles with compositions similar to clinically-used LNPs, storage in RNAse-free PBS containing 10% (w/v) sucrose at -20 °C was able to maintain vaccine stability and in vivo potency at a level equivalent to freshly prepared vaccines following 30 days of storage. LNPs loaded with repRNA could also be lyophilized with retention of bioactivity.

Freeze-Drying of a Capsid Virus-like Particle-Based Platform Allows Stable Storage of Vaccines at Ambient Temperature.

The requirement of an undisrupted cold chain during vaccine distribution is a major economic and logistical challenge limiting global vaccine access. Modular, nanoparticle-based platforms are expected to play an increasingly important role in the development of the next-generation vaccines. However, as with most vaccines, they are dependent on the cold chain in order to maintain stability and efficacy. Therefore, there is a pressing need to develop thermostable formulations that can be stored at ambient temperature for extended periods without the loss of vaccine efficacy. Here, we investigate the compatibility of the Tag/Catcher AP205 capsid virus-like particle (cVLP) vaccine platform with the freeze-drying process. Tag/Catcher cVLPs can be freeze-dried under diverse buffer and excipient conditions while maintaining their original biophysical properties. Additionally, we show that for two model cVLP vaccines, including a clinically tested SARS-CoV-2 vaccine, freeze-drying results in a product that once reconstituted retains the structural integrity and immunogenicity of the original material, even following storage under accelerated heat stress conditions. Furthermore, the freeze-dried SARS-CoV-2 cVLP vaccine is stable for up to 6 months at ambient temperature. Our study offers a potential solution to overcome the current limitations associated with the cold chain and may help minimize the need for low-temperature storage.

New crop of mRNA vaccines aim for accessibility

The article discusses the clinical trials of new mRNA vaccines to combat COVID-19 that will be easier to store and cheaper, including one from China in a phase 3 trial. Vaccines produced by the Pfizer-BioNTech and Moderna rely on mRNA to direct cells to produce spike, a protein on SARS-CoV-2's surface, which are of high price and need to be stored at extremely low temperatures.

Demystifying mRNA vaccines: an emerging platform at the forefront of cryptic diseases.

Messenger RNA (mRNA) vaccines have been studied for decades, but only recently, during the COVID-19 pandemic, has the technology garnered noteworthy attention. In contrast to traditional vaccines, mRNA vaccines elicit a more balanced immune response, triggering both humoral and cellular components of the adaptive immune system. However, some inherent hurdles associated with stability, immunogenicity, in vivo delivery, along with the novelty of the technology, have generated scepticism in the adoption of mRNA vaccines. Recent developments have pushed to bypass these issues and the approval of mRNA-based vaccines to combat COVID-19 has further highlighted the feasibility, safety, efficacy, and rapid development potential of this platform, thereby pushing it to the forefront of emerging therapeutics. This review aims to demystify mRNA vaccines, delineating the evolution of the technology which has emerged as a timely solution to COVID-19 and exploring the immense potential it offers as a prophylactic option for other cryptic diseases.

COVID 19 vaccine distribution solution to the last mile challenge: Experimental and simulation studies of ultra-low temperature refrigeration system.

Most COVID-19 vaccines require ambient temperature control for transportation and storage. Both Pfizer and Moderna vaccines are based on mRNA and lipid nanoparticles requiring low temperature storage. The Pfizer vaccine requires ultra-low temperature storage (between -80 °C and -60 °C), while the Moderna vaccine requires -30 °C storage. Pfizer has designed a reusable package for transportation and storage that can keep the vaccine at the target temperature for 10 days. However, the last stage of distribution is quite challenging, especially for rural or suburban areas, where local towns, pharmacy chains and hospitals may not have the infrastructure required to store the vaccine. Also, the need for a large amount of ultra-low temperature refrigeration equipment in a short time period creates tremendous pressure on the equipment suppliers. In addition, there is limited data available to address ancillary challenges of the distribution framework for both transportation and storage stages. As such, there is a need for a quick, effective, secure, and safe solution to mitigate the challenges faced by vaccine distribution logistics. The study proposes an effective, secure, and safe ultra-low temperature refrigeration solution to resolve the vaccine distribution last mile challenge. The approach is to utilize commercially available products, such as refrigeration container units, and retrofit them to meet the vaccine storage temperature requirement. Both experimental and simulation studies are conducted to evaluate the technical merits of this solution with the ability to control temperature at -30 °C or -70 °C as part of the last mile supply chain for vaccine candidates.