Ending the refrigeration of vaccines? New technique could remove need for cold chain logistics
The researchers encapsulated live virus vaccines with a dissolvable crystalline material called MOFs (metal organic frameworks), which has been shown to protect the integrity of vaccines for up to 12 weeks at 37 degrees (such vaccines, without refrigeration, would normally only last a few days).
The approach could help vaccines reach remote towns in Australia as well as in developing countries. CSIRO scientists are now looking at proving the approach for other animal and human vaccines, including mRNA vaccines.
The search for a universal stabilization formula
The World Health Organization estimates that at least 50% of vaccines are wasted globally each year, with a lack of facilities and temperature control the major cause.
There are two common approaches to protecting vaccines from heat. The first is modifying the vaccine, which is a complex and laborious process which may still only result in limited shelf life at high temperatures. The second is to look at stabilizing agents, but this can still pose challenges on how to scale up the solution.
“For live viral vaccines, their complex molecular composition further increases their susceptibility to stresses such as temperature, exposure to light and freeze-thawing," note the CSIRO researchers. "Due to their compositional diversity, finding a universal vaccine stabilization formula has been challenging.”
The researchers say their ‘world-first’ approach of stabilizing vaccines with MOFs is simple, rapid, scalable and cost-effective.
In their study published in Acta Biomateriala, they focused on two different types of live viruses as proofs of concept: a Newcastle Disease vaccine designed to protect poultry and a strain of Influenza A.
When MOFs were formed around the vaccines they helped protect the vaccine molecules from heat stress: with the porous crystalline materials effectively creating a ‘scaffold’ around the vaccine. A solution was then used that dissolved the MOF for administration of the vaccine.
The research compared three NDV vaccines versions: a control NDV vaccine; a novel trehalose (T) and skim milk (SM), stabilized freeze-dried MOF vaccine, ZIF-8@NDV+T/SM; and a non-encapsulated, freeze-dried NDV+T/SM composite.
Over a 12 week period, the vaccines were kept at 4 degrees, room temperature, and 37 degrees.
The control NDV vaccine lost all viability at room temperature by 12 weeks and 37 degrees by four weeks. Comparing the freeze-fried counterparts the MOF encapsulated ZIF-8@NDV+T/SM demonstrated ‘significant enhancement in stability’ of the NDV+T/SM composite especially at RT and 37 °C up to 12 weeks.
MOF research
MOFs are a class of porous materials formed by the co-ordination of metal ions and organic bridging ligands, making an open, ordered and continuous network. Biomimetic-mineralization is a self-assembly process, in which MOFs can grow on biological materials and living organisms.
MOFs have been widely investigated as biomimetic coatings for carbohydrates, amino acids, proteins, and even cells. Importantly, the MOF coatings are shown to enhance the thermal and chemical stability of the encapsulated biomolecules in challenging environments.
Recently, MOFs have been deployed for advancement in the field of immunology. Proof-of-concept studies have also shown the feasibility and promising potential of MOFs for model subunit and whole pathogen vaccine advancement.
“In our pioneering work, we have validated the concept by demonstrating MOF biomimetic mineralization of a commercial live viral vaccine, providing it with remarkable stability while maintaining its ability to replicate and therefore induce immunity," note the researchers in the study.
