Research Report 2010 2011 - Helmholtz-Zentrum für ...

38 RESEARCH REVIEWS | Novel Nanoparticle-based Technology Platform for the Delivery of Vaccine Antigens
particles. 11 In addition, it was shown that carrier size could
play a role in determining the type of response induced.
Virus-like particles induced IFN-γ and cell-mediated type
1 responses, whereas larger beads mostly induced type 2
responses. 12
However, strategies for transdermal vaccination that reduce
the protective barrier function of the stratum corneum for a
significant period of time are intrinsically problematic due
to the risk of invasion of pathogens. This imposes a limit to
such methods for mass vaccination campaigns in countries
with critical hygienic conditions and calls for alternatives
that leave the stratum corneum intact. Therefore, the transappendage
pathway seems to be an appealing alternative to
circumvent the stratum corneum barrier and directly target
Langerhans cells via the hair follicles.
Fig 3. Overlay of transmission and fluorescence image of
a longitudinal section of skin from a porcine ear. Green
fluorescent nanoparticles (ca. 500 nm) applied to the ear
accumulate in the opening of the hair follicle. Photo: HZI
Development of pollen-mimetic vaccine particles
Scientists from HIPS and Saarland University, in collaboration
with the Charité Universitätsmedizin Berlin¸
recently showed that nanoparticles accumulate selectively
in the openings of hair follicles. 13 These nanoparticles were
made of the biodegradable and biocompatible polymer
polylactic-co-glycolic acid (PLGA) using polyvinyl alcohol
as a stabilizer.
A plain aqueous nanoparticle suspension as well as a
hydrogel formulation that was massaged into pig ear skin
in vitro, permeated deeper and to a greater extent into hair
follicles than an aqueous solution applied with similar
physical force. It was hypothesized that this is due to a passive
targeting effect, elicited by the nano-scale size of the
delivery device. We could further show that such particles
may release different encapsulated compounds that then
enter the stratum corneum.
As outlined above, the trans-follicular route appeals as a
very attractive and safe strategy for the delivery of vaccine
antigens to APCs. Hair bulbs are also an excellent reservoir,
being only slowly cleared by hair growth and sebum production.
16 An activation of the APCs via this route is a commonly
occurring phenomenon in allergic contact dermatitis
in people allergic to pollen antigens. In fact, pollen can be
considered as a micrometer sized carrier that accumulates
in the follicle opening, sebaceous gland or dermatoglyphs
(skin folds). Antigen release from the pollen is triggered by
a moist atmosphere with sufficient humidity, such as occurs
on the skin by sweating. The idea is now to mimic pollen
delivery in order to vaccinate across the intact skin barrier.
Therefore, we are currently working to create pollen-mimetic
carriers allowing antigens to be stably encapsulated in
order to target the hair follicles. This would allow releasing
the antigen at the site of action in a controlled fashion in
order to activate skin APCs, thereby eliciting an effective
humoral and cellular immune responses. Co-encapsulation
of different adjuvants would enable to strengthen the
overall responses, as well as to modulate them according to
the specific needs. First experiments show that the model
antigens can be encapsulated into PLGA particles. These
particles can be freeze-dried to be stored in a stable form.
They can then be re-dispersed in water directly before the
experiment to be tested in vitro or in vivo. The particles shall
later be formulated as a gel or lotion making them easy to
manufacture, acceptable to patients and safe to use.