Malvern Panalytical is committed to providing support for all vaccine development platforms. Malvern Panalytical and Leukocare recently announced their collaboration on formulation development for Covid-19 vaccine stabilization. This is a testament to Malvern Panalytical’s combined profound knowhow and analytical expertise.

Less than a year after the SARS-CoV-2 virus was initially identified and sequenced, the US FDA granted emergency use authorization to Moderna and Pfizer/BioNTech for their mRNA vaccines, a new platform for humans. The mRNA vaccine delivers a nucleoside modified messenger RNA (mRNA), and the human host cell machinery uses this mRNA as a template to produce CoV S proteins. After the 1st and 2nd vaccine doses, the host learns how to make antibodies specifically against the S proteins. If we are then infected with SARS CoV-2 virus, our immune system rapidly mobilizes and we are very likely to avoid serious illness, hospitalization and death from COVID-19.

The use of mRNA has several beneficial features over conventional and advanced vaccine platforms such as subunit, killed and live attenuated virus, and DNA-based vaccines.

They are safe

mRNA is a non-infectious, non-integrating platform, so there is no potential risk of infection or insertional mutagenesis.

They have high efficacy

Carrier molecules are used for efficient in vivo delivery. This means rapid uptake and expression in the cytoplasm. mRNA is the minimal genetic vector and mRNA vaccines can be administered repeatedly to induce both B- and T-cell responses.

They can be quickly produced

mRNA vaccines have the potential for rapid, inexpensive and scalable manufacturing, mainly owing to the high yields of in vitro transcription reactions.

What are they made of?

An mRNA vaccine consists of nucleoside modified mRNA coding for a specific viral antigen, a delivery carrier, typically lipid nanoparticles (LNPs), and inactive ingredients. Nucleoside modification has been found to increase the biological stability of mRNA, and an example is the substitution of uridine by pseudouridine. This modification can occur in vivo and increases the half-life of the mRNA. Further, in vitro transcription used to generate mRNA easily achieves this substitution.

LNPs have been found to be the most effective mRNA formulation/delivery approach and function to protect the mRNA from degradation when injected into the patient and to promote entry of the mRNA into cells. LNPs typically consist of four components: an ionizable cationic lipid, which promotes self-assembly into virus-sized (~100 nm) particles and enables endosomal release of mRNA to the cytoplasm; lipid-linked polyethylene glycol (PEG), which increases the half-life of formulations; cholesterol, a stabilizing agent; and naturally occurring phospholipids, which support the lipid bilayer structure.

Inactive ingredients such as salts, sugars, and stabilizing acids are added to achieve formulation stability during transport and storage.

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Lipid particles are submicron capsules with either an aqueous core, e.g. liposomes; or solid or amorphous core surrounded and stabilized by lipid layers, e.g. LNPs loaded with nucleic acids.

In 2018, the U.S. FDA published a guidance for industry on the development of liposome drug products, identified in it are several critical quality attributes (CQAs) that have to be addressed. Nanoparticle characterization CQAs on particle size, particle size distribution and concentration can be measured using Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA). These techniques are both orthogonal and complimentary in addressing this. Surface charge, another CQA listed in the guidance, could be probed using Electrophoretic Light Scattering (ELS), a measure of particles colloidal stability CQA.

Further reading