By Will Soutter
Topics Covered
Introduction
Nanovaccines
Oral delivery
Nasal delivery
Intra-dermal
injection
Nanobeads
Potential Issues with
Nanovaccines
Recent Developments
Conclusions
References
Introduction
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.
.jpg)
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
Nanovaccines
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.
.jpg)
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.
Recent Developments
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.
Conclusions
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.
References