Push for more stable vaccines

“Scientists at Oxford University have found a way of keeping vaccines stable without refrigeration,” the BBC website has reported.

The news is based on research on using two special membranes to dry the viral particles used in vaccines in order to keep them stable when stored at warm temperatures. Normally these viral substances cannot stand warmer atmospheres for more than a few weeks, which means they need to be kept refrigerated. The new techniques tested were shown to increase the shelf life of viral substances by several months, meaning they could help reduce the practical problems faced by vaccination programmes in the developing world.

This is potentially a very useful development as it offers the hope that doctors will be able to distribute vaccines more easily in the rural areas of developing countries where refrigerated storage for vaccines can be problematic and costly. This will be of particular importance for the distribution of any HIV and malaria vaccines that may be developed, as these illnesses are very common in some hot, remote parts of Africa.

Where did the story come from?

Dr Robert Alcock and colleagues from Cambridge Biostability Ltd, the University of Oxford and Nova Bio-Pharma carried out this research. The study was funded by a grant from the Grand Challenges in Global Health initiative of the Bill and Melinda Gates Foundation. The study was published in the peer-reviewed medical journal Science Translational Medicine .

This study was covered in detail by the BBC.

What kind of research was this?

Many vaccines work by using a weakened form of a live virus. Injecting someone with the vaccine triggers the immune system into creating antibodies that protect against the full-strength virus. Some vaccines are made by injecting only part of a virus's DNA into the body. This DNA is contained within a ‘vector’, which is a substance that allows viral proteins to develop inside the body. The body’s immune system makes antibodies to protect itself against these proteins, so that if the person is exposed to these proteins on the real virus they are already protected.

Vaccines are not very stable and need to be stored cold. Keeping vaccines refrigerated is estimated to account for up to 14% of the cost of a vaccine. There are also important practical implications of the need to refrigerate vaccines in some developing countries. These areas often have the greatest need for immunisation but lack the reliable electricity supply needed to store vaccines.

Many scientists are trying to develop new viral vector-based vaccines for malaria, tuberculosis, HIV-AIDs and influenza. The authors of this paper say there must also be moves to make these vaccines more stable at higher temperatures in order to increase the overall efficiency of vaccination programmes.

In this laboratory study the researchers looked at whether they could make vaccines more stable in warmer conditions. They based their research on a type of chemistry involving different types of sugars, suggesting that these sugars would stabilise the vaccine molecules. Theoretically, combining the viral molecules with sugars immobilises them and prevents any chemical reaction that might break down the vaccine.

What did the research involve?

The researchers used two viral vaccine vectors, called AdHu5 and MVA, both of which are unstable at warm temperatures. They looked at how stable the two viral vectors were by storing them at different temperatures. They then also tested how infective they were by measuring the immune response they elicited in vaccinated mice.

Vaccines are usually dried for storage then reconstituted in liquid for injection. Two sugars, sucrose and trehalose, are commonly used as stabilising agents in vaccines because they can protect the live vaccine from breaking down. This research tested an alternative technique where the viral vectors were slowly dried using a glass fibre or polypropylene membrane at room temperature. The researchers then tested if these dried vaccines could be reconstituted easily and whether they were as effective as traditional cold-stored vaccines.

Finally, they looked at the infective properties of the membrane-dried viral vectors under different storage conditions, as viral vectors need to remain infective in order to create immunity in the body.

What were the basic results?

The researchers found that the viral vector AdHu5 was not infectious, and therefore ineffective, when stored at 37˚C or 45˚C for one week. The MVA viral vector was stable at these temperatures for about a month.

The researchers found that MVA could be dried without using membranes and still retain its infectivity when reconstituted, even if it was dried without the sugar stabilisers. However, AdHu5 needed to be dried with the sugar stabilisers in order to remain infective. Adding sugars to AdHu5 preserved its full infectivity after reconstitution.

The researchers also found that AdHu5 could be stored for up to six months and at temperatures up to 45˚C if dried on a glass fibre membrane with the sugar stabilisers. Drying on a polypropylene membrane allowed it to be stored for six months at temperatures up to 25˚C.

The MVA viral vector could be stored for up to 12 months at 37˚C. At 45˚C this viral vector was stable for at least four months, but by 12 months it had lost its infectivity. The stability of MVA did not differ on either membrane.

How did the researchers interpret the results?

The researchers suggest that the new technique can make viral vectors stable for four to six months at temperatures up to 45˚C. They say that the doses deposited onto membranes in their proof-of-concept study were close to those that are used in a clinical setting.

The researchers propose that an attachment containing the membrane with the dried vaccine could be fitted to the end of a standard syringe as part of an all-in-one, ready-to-inject vaccine delivery device. The liquid in the syringe would reconstitute the viral vector in the attachment to create a complete vaccine for immediate injection. They suggest that this technology may “allow low-tech distribution routes in rural areas, potentially enabling better penetration of disease prevention measures in resource-poor settings”.

Conclusion

This was a proof-of-concept study that showed that viral vector stability at warm temperatures could be increased by slowly drying vaccines suspended in sugar stabilisers onto special filter-like membranes.

This study was performed with model viral vectors that can have DNA inserted into them to make them work as vaccines for specific diseases. Further work is needed to characterise the effect of the technique on the storage conditions needed for vaccines used for specific diseases.

This development is potentially very useful as it may lead to improvements in the availability and effectiveness of vaccination programmes in areas of the world with fewer resources.