The outbreak and ongoing pandemic of COVID-19 have had a significant impact on the world, but at the same time, it has also shown us the enormous potential of mRNA technology.
Stability is one of the main challenges in developing mRNA vaccines. The two mRNA vaccines currently on the market both need to be stored and transported at strict low temperatures (-70°C and -20°C), which undoubtedly increases the difficulty and cost of storing and transporting the vaccines, significantly limiting the large-scale promotion and popularization of vaccines.
One of the most commonly used methods to improve stability is to prepare the formulation into a lyophilized form. This time, the product team of AVT Ltd analyzed in depth the lyophilized cytomegalovirus (CMV) vaccine mRNA-1647 currently in Phase III clinical trials by Moderna, hoping to provide some reference and inspiration to our readers.
On October 20, 2021, Moderna registered its cytomegalovirus (CMV) mRNA vaccine mRNA-1647 in a Phase III clinical trial on ClinicalTrials.gov for efficacy, safety, and immunogenicity in healthy female subjects aged 16-40.
According to information on the ClinicalTrials.gov website, the clinical trial is currently underway (as of May 27, 2022) and plans to recruit 6,900 subjects who will receive the mRNA-1647 vaccine by intramuscular injection (IM) on days 1, 57, and 169. The trial is expected to be completed on January 29, 2023.
mRNA-1647 contains six mRNA sequences, including five encoding pentameric complexes and one encoding the gB antigen. Pentameric complexes are essential for CMV entry into various cells, including epithelial cells, while gB plays an important role in CMV entry into all susceptible cells, including fibroblasts. Vaccines that produce an immune response against pentameric complexes and gB may block CMV entry into a range of target cell types, preventing primary and congenital infections.
mRNA-1647 instructs the body's own cells to produce and generate functional antigens, simulating the antigens presented to the immune system by CMV during natural infection. Phase II studies have shown that neutralizing antibody titers increased in a dose-dependent manner in both seronegative and seropositive subjects after the first dose of vaccine was administered. By the seventh month after injection, the vaccine was able to elicit effective and persistent neutralizing antibody titers in both epithelial cells and fibroblasts.
mRNA-1647 uses the same lipid nanoparticle (LNP) as mRNA-1273 and mRNA-1653 (hMPV-PIV3 virus vaccine). Since previous products have established some clinical and regulatory precedents, a complete system for identifying, testing, and producing lipid formulations may play an important role in accelerating the entry of mRNA-1647 into clinical trials.
First-in-human trials typically involve a limited number of participants and clinical trial sites, and sometimes use less-than-ideal formulations. Developing improved storage conditions and clinical plans is done in parallel.
mRNA-1647 was provided as a frozen liquid formulation in the Phase I study, but was changed to a lyophilized formulation beginning in the Phase II study. It has been reported that lyophilized mRNA-1647 remains stable for 18 months at refrigerated temperatures. Comparing the shelf life and storage conditions of the two currently marketed COVID-19 mRNA vaccines, the role of lyophilization in improving formulation stability can be said to be significant.
-90°C to -60°C frozen
12 months, use within 30 days after transfer to 2-8°C refrigeration
-25°C to -15°C frozen
9 months, use within 30 days after transfer to 2-8°C refrigeration
18 months (Phase III clinical data)
Lyophilization is the most commonly used method for transporting and storing many drugs. However, the stress produced by crystallization and vacuum dehydration during lyophilization may reduce the stability of large molecules or LNPs, leading to loss of biological activity. It has been reported that adding appropriate cryoprotectants, such as trehalose, sucrose, and mannitol, can maintain the stability of LNPs in a specific formulation. Pfizer has initiated a Phase III study comparing the safety and tolerability of lyophilized BNT162b2 formulations to its frozen liquid BNT162b2 formulations.
For sucrose or trehalose for sale and further analysis of lyoprotectants' applications and mechanisms, please follow AVT's official WeChat account or contact us for additional communication.
Cytomegalovirus (CMV) is a common pathogen belonging to the herpesvirus family. Congenital CMV infection is caused by infected mothers transmitting the virus to unborn babies. In the United States, CMV is the leading cause of birth defects, with approximately 25,000 newborns being infected with CMV each year, and approximately 20% of infected babies having birth defects. Currently, there is no approved vaccine to prevent CMV infection.
AVT provides injection-grade bioprotectants, such as trehalose, sucrose, TRIS, HEPES, and buffer salts, that are ultra-low in endotoxins and comply with various pharmacopoeia standards worldwide. This helps facilitate the production and application of biological preparations such as mRNA-LNPs, liposomes, monoclonal antibodies, ADCs, and more.