Nanoparticle based vaccines: a potentially new addition to the “vaccine menu”?

Vaccine bottle held in gloved hand with needle inserted
Photo by Mufid Majnun on Unsplash

A versatile and highly effective flu vaccine required in tiny amounts might be just around the corner: too good to be true? Kevin Boyle looks at recent advances. 

For around 70 years, flu vaccines have mostly been made the same way – using chicken eggs. The virus is injected into the eggs and incubated for a few days allowing replication to occur. The virus is then extracted and deactivated, at which point it is ready for use in the vaccine. The deactivated form of the virus is the vital ingredient that primes immune cells ready to fight any flu virus that the body might encounter. 

However, the above process has its drawbacks, namely that it relies on having a large number of eggs – Novartis (a multinational pharmaceutical company) requires around half a million per day – and the manufacturing process is time consuming. There is also uncertainty associated with flu vaccine production due to how quickly and unpredictably the virus changes through a process known as mutation. Therefore, in order to be effective, the vaccine must be modified each year. There is an element of guess work associated with the process and the effectiveness isn’t easy to predict. Compared with the COVID-19 vaccines (>90% effective), the flu vaccines are 40-60% effective. Even though they are different viruses, there is clearly room for improvement. It should be noted that flu vaccines have also been made from cells or recombinant proteins instead of eggs, but these methods are nowhere near as common. There are also flu vaccines that use a weakened form of the virus rather than the deactivated form. These are mostly confined to nasal sprays.

There are four types of flu viruses: A, B, C and D, of which, types A and B cause most human flu related illness. Type A is responsible for around 75% of seasonal flu cases, due to its fast mutation rate and numerous hosts, which include pigs, chickens and birds. It was also responsible for causing the Spanish flu pandemic in 1918 and swine flu in 2009. There are various subtypes of the above-mentioned virus types, which are determined by the proteins found on the virus surface. The surface proteins are essential for the virus to enter the host cells. The type A virus has hemagglutinin (H) and neuraminidase (N) proteins on its surface. Variation in these proteins has led to 131 known subtypes, but there are only two commonly found seasonally in humans: H1N1 and H3N2. These two subtypes are targets for the vaccines.

Associate professor of bioengineering Dr Jonathan Lovell in collaboration with research teams from the US, Canada and China have designed an experimental flu vaccine using nanotechnology and recombinant proteins, which has shown promising results in preclinical trials. This is the first flu vaccine of its kind.

The use of nanotechnology has many benefits. Firstly, the scale (a nanometer is one billionth of a meter) of nanotechnology makes the use of nanoparticles attractive in science and technology. Moreover, it is very applicable to medicine, as the nanoparticles are similar in size to cellular components. Nanotechnology also provides flexibility; the composition, size and shape of individual atoms can be easily controlled and manipulated. This opens up a world of new possibilities. As a result, nanoparticles have been utilised in areas such as drug delivery, gene therapy, and vaccine development. Nanoparticles are extremely topical; they are used in both the Pfizer and Moderna COVID-19 vaccines.

Many different materials can be used as nanoparticles. Lovell’s team specifically used a liposome nanoparticle, which are spherical particles that have been used as drug delivery and adjuvant systems for years; an adjuvant is an ingredient in the vaccine that helps create a stronger immune response. Liposomes are highly efficient at protecting the drug from degradation in the body and are highly malleable. Modifications can be made to their size, charge and surface, which can create better liposomal interactions with the cell. Lovell’s group reported that their liposome, cobalt-porphyrin-phospholipid (CoPoP), converts virus proteins into a more potent form on the liposome surface, thus improving cellular interaction. As a result, there is an increased uptake of the drug, which in turn generates a stronger immune response and a more targeted vaccine. 

Alongside the nanoparticles, recombinant proteins are the other main component of the experimental vaccine. These proteins are produced in a process where two or more DNA strands are firstly fused together before being inserted into a host cell. The host then produces a recombinant protein from the information inserted. This method allows for great flexibility as scientists can make a huge range of recombinant protein combinations. For example, Lovell’s group produced a “multivalent” nanoparticle consisting of ten proteins that target different strains of the flu virus and showed that it was very effective against the bird flu. Given that recombinant proteins are synthetically produced, their quantity is not reliant on constant egg supply, which makes vaccine production faster, easier and more reliable than traditional methods.

There is more good news… a low dose of the vaccine, as little as two nanograms, was shown to trigger a similar immune response to vaccines with up to1,000 times higher doses. This is known as “dose-sparing effect”, which is another advantage of this vaccine technology, as it increases the efficiency of the manufacturing process, and could become vital if there is a vaccine shortage during a pandemic. 

Overall, based on their initial results, there is confidence that a more efficient flu vaccine than what is currently on the market is possible, which could potentially save hundreds of thousands of lives worldwide annually. However, it should be noted that only preliminary experimental results have been obtained and the vaccine is yet to be trialled on humans. The technology used in the development of the flu vaccine is said to have created a “vaccine platform” from which new vaccines could be made to fight other diseases, such as HIV (Lovell is also involved with this). This creates an exciting development to watch out for in the future.

Written by Kevin Boyle and edited by Natasha Kisseroudis

Kevin studied Chemistry as an undergrad and later pursued a PhD in Organic Chemistry at the University of Edinburgh before later undertaking a Masters in Chemical Biology at Imperial College London. He now works as a full-time Chemistry tutor. 

You can find him on LinkedIn @Kevin Boyle 

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