Scientists at King's College London have demonstrated the
ability to deliver a dried live vaccine to the skin without a
traditional needle, and shown for the first time that this
technique is powerful enough to enable specialised immune cells in
the skin to kick-start the immunising properties of the
vaccine.
The researchers say although it is an early study, this
important technical advance offers a potential solution to the
challenges of delivering live vaccines in resource-limited
countries globally, without the need for
refrigeration.
A cheaper alternative to hypodermic needles, it would also
remove safety risks from needle contamination and the pain-free
administration could lead to more people taking up a vaccination.
The researchers add that it could have an impact beyond infectious
disease vaccination programmes, for example managing autoimmune and
inflammatory conditions such as diabetes.
HIV, malaria and TB represent major global health challenges.
Although promising research is underway to develop vaccines for
these diseases, considerable stumbling blocks remain for countries
where transporting and storing live vaccines in a continuously cold
environment (around 2°C to 8°C or below) would not be possible. If
a cold chain cannot be maintained for a live vaccine there is a
high risk it could become unsafe and lose
effectiveness.
The team at King's used a silicone mould developed by US company
TheraJect to create a microneedle array - a tiny disc with several
micro-needles made of sugar which dissolve when inserted into the
skin. The team formulated a dried version of a live modified
adenovirus-based candidate HIV vaccine in sugar (sucrose) and used
the mould to create the microneedle array. They found that the
dried live vaccine remained stable and effective at room
temperature.
To test the effectiveness of the microneedle array, they applied
it to mice. Using imaging (in collaboration with Professor Frederic
Geissmann, King's College London) they observed how the vaccine
dissolved in the skin and were able to identify for the first time
exactly which specialised immune cells in the skin 'pick up' this
type of vaccine and activate the immune system. The researchers
found the first evidence that a subset of specialised dendritic
cells in the skin were responsible for triggering this immune
response.
The immune response generated by the dried microneedle vaccine
(kept at room temperature) was equivalent to that induced by the
same dose of liquid vaccine that had been preserved at -80°C and
delivered by a traditional needle vaccine
method.
Dr Linda Klavinskis of King's College London said: "We have
shown that it is possible to maintain the effectiveness of a live
vaccine by drying it in sugar and applying it to the skin using
microneedles - a potentially painless alternative to hypodermic
needles. We have also uncovered the role of specific cells in the
skin which act as a surveillance system, picking up the vaccine by
this delivery system and kick-starting the body's immune
processes.
"This work opens up the exciting possibility of being able to
deliver live vaccines in a global context, without the need for
refrigeration. It could potentially reduce the cost of
manufacturing and transportation, improve safety (as there would be
no loss in potency), and avoids the need of hypodermic needle
injection, reducing the risk of transmitting blood-borne disease
from contaminated needles and syringes.
"This new technique represents a huge leap forward in overcoming
the challenges of delivering a vaccination programme for diseases
such as HIV and malaria. But these findings may also have wider
implications for other infectious disease vaccination programmes,
for example infant vaccinations, or even other inflammatory and
autoimmune conditions such as diabetes."
The published study from King's College London is part of a
larger project funded by the Bill & Melinda Gates Foundation
linking other groups, including those at Imperial College London
and Royal Holloway University of London, who are working on other
aspects of HIV vaccination.
The paper, Langerin
negative dendritic cells promote potent CD8+ T-cell
priming by skin delivery of live adenovirus vaccine microneedle
arrays, is published in Proceedings of the National
Academy of Sciences.