By Will Soutter
Potential Issues with Nanovaccines
Vaccination is one of the most important parts of modern medicine. Many infectious diseases which used to be almost guaranteed to be fatal are now easily prevented, and many have been eradicated altogether.
Nanotechnology is likely to have widespread implications in medicine, and vaccines are no exception. This article explores some of the technologies being investigated by nanotechnology researchers, which could have a profound impact on vaccinations and the wider medical world.
Figure 1. Vaccines often consist of dead or partial viruses, which stimulate an immune response in the body, preparing the immune system to deal more effectively with a real infection. As our understanding of nanotechnology increases, its principles are being applied to design more effective vaccines. Image credit: ATG.WA.gov
One of the most promising areas of medicine where nanotechnology could have a big impact is in drug delivery, which is a very important part of vaccinations, and systems to get antigens into the body without needing an injection could drastically increase the availability of vaccinations, particularly in developing countries where access to trained medical personnel is limited.
Delivery systems can also protect the antigen until it reaches the most effective place in the body, allowing the dose to be lowered, which will reduce the side effects for the patient, and, importantly, reduce the cost.
Some novel methods of administering vaccines which nanotechnology is making viable include:
Oral delivery - antigens are often fragile, and can be damaged by digestive juices when taken orally. By encapsulating the dose in polymer nanoparticles, the active vaccine material could be preserves until it reaches the bloodstream. The overall dose may have to be higher than normal, however, as some of the vaccine will not be absorbed by the body. It is important, therefore, to make sure that side effects are under control, and the fate of the nanoparticles and the drug is understood.
Nasal delivery - nanoemulsions of vaccines can be safely inhaled in a nasal spray. This is a convenient method of delivery, which does not suffer from the dosing problems of oral delivery. Nanoemulsions are also stable at room temperature for relatively long periods of time, which would allow them to be distributed to remote locations and developing countries more easily. They have been shown to be effective in administering hepatitis B vaccinations in animal trials, although more study is needed to determine the effects on patients with allergies or respiratory problems.
Intra-dermal injection - this is the conventional method of administering vaccines. Although the less invasive oral and nasal delivery routes would be preferred most of the time, there will be some cases where an injection is necessary, and nanotechnology can still help to improve this technique. Vaccines are injected in combination with an inert material called an adjuvant, which causes the vaccine to pool under the skin and controls its release into the bloodstream. Using biodegradable nanoparticles as the adjuvant could allow the release rate to be tailored more precisely to the immune system of the patient - initial trials show that this improves the immune system's response to the vaccine.
Nanobeads - these are a possible way around the need for separate adjuvants when administering vaccines. By attaching the antigen directly to solid, inert beads, around 40nm in diameter, the immune response is greatly improved - these nanobead vaccines can also be used to treat infection as well as prevent it.
Figure 2. Vaccinations are currently administered via an injection, and require refrigeration to remain stable for long periods of time. Nanotechnology could make different delivery routes possible, making vaccines easier to transport and administer. Image credit: BT.CDC.gov
Potential Issues with Nanovaccines
As with all novel medicines, significant proof of efficacy and safety is required before even small trials with human patients can begin. The main concerns with nanovaccine technologies are:
- variations in toxicity/biocompatibility with nanoparticle size and shape
- reproducibility of nanoformulations on a large scale
- toxicity issues, particularly long-term accumulation in organs
The toxicity of nanoparticles is hard to assess, particularly when trying to rapidly screen a number of nanoformulations for vaccines or other drugs. Many of the adverse effects of nanoparticles on humans are likely to result from long-term, low-level exposure, which is difficult to measure, and requires very long trials to determine.
Researchers are trying to develop higher throughput tests for chemical signatures which appear in the short term which could be indicators of longer term problems. These are difficult to get accurate, however, and our understanding of the long term effect of nanoparticle exposure is still limited.
As well as improving the efficacy and availability of conventional vaccines, nanotechnology is also helping medical researchers to design vaccines for diseases we currently have no way to prevent, and to create vaccines that work without using any real viral material.
In July 2012, researchers from Arizona State University developed a method for constructing a completely synthetic virus using a DNA scaffold. This results in a similar immune response to dead or partial viruses, as the nanostructured synthetic material is a similar size and shape, but without the same associated risks.
Nanotherapeutics, a biopharmaceutical company from Florida, USA, is working with academic partners to develop a nanoparticle-based vaccine for HIV. The vaccine is designed to be ingested orally, which is not possible with current vaccines as they break down in the digestive tract. This would make the vaccine much easier to administer to populations in the developing world, where HIV infection is a major problem.
In the next few decades, nanotechnology will have a big impact on all aspects of medicine. The application of nanotechnology to vaccines will make them more effective and less invasive, and may provide opportunities to develop new vaccines for unpreventable or uncurable diseases.
Perhaps most importantly, nanotechnology will allow formulations of vaccines which are stable enough to be distributed without refrigeration to villages in the developing world, where access to medical facilities is very limited. This could save many lives, and slow the spread of HIV, malaria, and other major infectious diseases.