Addressing the Cold Reality of mRNA Vaccine Stability

Crommelin, Daan J.A.; Anchordoquy, Thomas J.; Volkin, David B.; Jiskoot, Wim; Mastrobattista, Enrico

doi:10.1016/j.xphs.2020.12.006

Cited by 376 publications

(324 citation statements)

References 19 publications

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“…Vaccine‐manufacturing capacity is physically and geographically limited, especially with regard to new technological platforms. For example, technologies such as the mRNA technology used by Moderna and Pfizer in their COVID‐19 vaccines are not readily found outside of a small number of high‐income countries (HICs) 18 . With respect to intellectual property (IP) and manufacturing capacity, IP rights are a barrier to expanding manufacturing capacity for many medical products, especially solid‐dose drugs.…”

Section: The Act‐accelerator Vaccines Pillarmentioning

confidence: 99%

International Collaboration to Ensure Equitable Access to Vaccines for COVID‐19: The ACT‐Accelerator and the COVAX Facility

2021

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Policy Points Equitable access to a COVID‐19 vaccine in all countries remains a key policy objective, but experience of previous pandemics suggests access will be limited in developing countries, despite the rapid development of three successful vaccine candidates. The COVAX Facility seeks to address this important issue, but the prevalence of vaccine nationalism threatens to limit the ability of the facility to meet both its funding targets and its ambitious goals for vaccine procurement. A failure to adequately address the underlying lack of infrastructure in developing countries threatens to further limit the success of the COVAX Facility. Context Significant effort has been directed toward developing a COVID‐19 vaccine, which is viewed as the route out of the pandemic. Much of this effort has coalesced around COVAX, the multilateral initiative aimed at accelerating the development of COVID‐19 vaccines, and ensuring they are equitably available in low‐ and middle‐income countries (LMICs). This paper represents the first significant analysis of COVAX, and the extent to which it can be said to have successfully met these aims. Methods This paper draws on the publicly available policy documents made available by the COVAX initiatives, as well as position papers and public statements from governments around the world with respect to COVID‐19 vaccines and equitable access. We analyze the academic literature regarding access to vaccines during the H1N1 pandemic. Finally, we consider the WHO Global Allocation System, and its principles, which are intended to guide COVAX vaccine deployment. Findings We argue that the funding mechanism deployed by the COVAX Pillar appears to be effective at fostering at‐risk investments in research and development and the production of doses in advance of confirmation of clinical efficacy, but caution that this represents a win‐win situation for vaccine manufacturers, providing them with opportunity to benefit regardless of whether their vaccine candidate ever goes on to gain regulatory approval. We also argue that the success of the COVAX Facility with respect to equitable access to vaccine is likely to be limited, primarily as a result of the prevalence of vaccine nationalism, whereby countries adopt policies which heavily prioritize their own public health needs at the expense of others. Conclusions Current efforts through COVAX have greatly accelerated the development of vaccines against COVID‐19, but these benefits are unlikely to flow to LMICs, largely due to the threat of vaccine nationalism.

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Section: The Act‐accelerator Vaccines Pillarmentioning

confidence: 99%

International Collaboration to Ensure Equitable Access to Vaccines for COVID‐19: The ACT‐Accelerator and the COVAX Facility

2021

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“…Undoubtedly, the new mRNA based COVID-19 vaccine formulations require stabilization at higher temperatures, as demanded by their storage, transport, and delivery across the world in billions of doses to contain the ongoing pandemic. Available information on the mRNA-1273 profile suggests the vaccine to be stable at −20°C up to 6 months while retaining its stability for about 30 days when kept under refrigeration (Businesswire, 2020a;Crommelin et al, 2021); thus, providing storage and shipping advantage over BNT162b2, which requires an ultra-freeze storage condition (−80 to −60°C) in which it remains stable up to 6 months, while retaining stability up to 5 days under refrigerated conditions (Crommelin et al, 2021;Philippidis, 2020). However, Pfizer and BioNTech claimed to develop temperature-controlled thermal shippers using dry ice to maintain the temperature within −70 to +10°C (Philippidis, 2020).…”

Section: Challenges and Opportunity Gaps In Rna Vaccine Development Imentioning

confidence: 99%

Perspectives on RNA Vaccine Candidates for COVID-19

Borah

Deb

Al-Shar’i

et al. 2021

Front. Mol. Biosci.

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With the current outbreak caused by SARS-CoV-2, vaccination is acclaimed as a public health care priority. Rapid genetic sequencing of SARS-CoV-2 has triggered the scientific community to search for effective vaccines. Collaborative approaches from research institutes and biotech companies have acknowledged the use of viral proteins as potential vaccine candidates against COVID-19. Nucleic acid (DNA or RNA) vaccines are considered the next generation vaccines as they can be rapidly designed to encode any desirable viral sequence including the highly conserved antigen sequences. RNA vaccines being less prone to host genome integration (cons of DNA vaccines) and anti-vector immunity (a compromising factor of viral vectors) offer great potential as front-runners for universal COVID-19 vaccine. The proof of concept for RNA-based vaccines has already been proven in humans, and the prospects for commercialization are very encouraging as well. With the emergence of COVID-19, mRNA-1273, an mRNA vaccine developed by Moderna, Inc. was the first to enter human trials, with the first volunteer receiving the dose within 10 weeks after SARS-CoV-2 genetic sequencing. The recent interest in mRNA vaccines has been fueled by the state of the art technologies that enhance mRNA stability and improve vaccine delivery. Interestingly, as per the “Draft landscape of COVID-19 candidate vaccines” published by the World Health Organization (WHO) on December 29, 2020, seven potential RNA based COVID-19 vaccines are in different stages of clinical trials; of them, two candidates already received emergency use authorization, and another 22 potential candidates are undergoing pre-clinical investigations. This review will shed light on the rationality of RNA as a platform for vaccine development against COVID-19, highlighting the possible pros and cons, lessons learned from the past, and the future prospects.

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“…Crommelin and colleagues wrote in a review article in The Journal of Pharmaceutical Sciences late last year. “Even a minor degradation reaction, anywhere along a mRNA strand, can severely slow or stop proper translation performance of that strand and thus result in the incomplete expression of the target antigen.”6…”

Section: A Near Miss?mentioning

confidence: 99%