Download Overview Possible Applications

Mucosal Vaccines
Using a novel targeting molecule to create
effective mucosal vaccines
Overview
Possible Applications
Our novel mimetic of the lectin Ulex europaeus agglutinin-1 from the
gorse bush, provides a means to develop effective mucosal vaccines
The potent cellular responses induced by the UEA-1 mimetic can be
harnessed for the development of vaccines against pathogens
including such as influenza, Staphylococcus aureus, Streptococcus
pneumoniae and HIV
The advantages of mucosal vaccination and the UEA-1 mimetic
Where an antibody-mediated response is vital for protection, as in the
case of influenza, we have shown that co-administration of saponin
adjuvants induces antigen-specific antibodies
Mucosal vaccination is an attractive option for controlling infectious
disease since mucosal vaccines are cheaper to manufacture, easy to
administer, and reduce the need for a ‘cold chain’ during transport.
However, the development of mucosal vaccines is hampered by several
factors including dilution of the vaccine in mucosal secretions, enzymatic
degradation and inefficient uptake across epithelial barriers
Our vaccine targeting
molecule is a low molecular
weight mimetic of the gorse
plant UEA-1 lectin
Effectively targeting nanoparticulate vaccines to immune cells with the
UEA-1 mimetic confers a number of advantages:
• Both UEA-1 and its mimetic bind with high affinity to M cells in the
gastrointestinal tract and the nasal-associated lymphoid tissue, enabling
increased uptake of targeted nanoparticles
• Nanoparticles can enhance the activation of immune responses and
increased uptake will enhance nanoparticle-driven immunity
We use a biotinylated form of
the UEA-1 mimetic to enable
conjugation with
antigens/adjuvants
•Since M cells are present in both the respiratory tract and
gastrointestinal tract, our technology can enhance the effectiveness
of both nasal and oral vaccines
(restimulated splenocytes)
*
*
Control
OVA
2
*
Control
OVA
15
10
10 2
Pam3Csk4
MPLA
CpG
Quil A
m
-1
A
U
E
+
A
O
V
VA
O
ND
OVA + UEA-1m + PS
+
+
A
O
V
U
+
O
P
S
S
P
A
S
PS
EA
O
-1
m
VA
+
+
-1
U
EA
+
VA
Antigen
PS
m
VA
O
PB
Biotin
S
0
ND
OVA + PS
10 0
OVA
0
Nasal and oral vaccination studies were
carried out on mice using (a)
nanoparticles (PS) that were coated with
both antigen (OVA) and the UEA-1
mimetic targeting molecule
10 4
5
B
Biotin
1
*
20
IFN (ng/ml)
IFN- (ng/ml)
Antigen
Biotin
3
(antigen-specific IgG)
10 6
*
**
Nasal immunisation
(d)
25
P
Biotin
5
4
Antigen
Nasal immunisation
(restimulated lymph node cells)
Antigen
Nanoparticle
(c)
Oral immunisation
IgG titre
(b)
O
V
(a)
OVA+UEA-1m +PS
Targeting nanoparticulate vaccines with the UEA-1 mimetic enhanced cellular immunity following oral (b) and
nasal (c) immunisation. When combined with immunostimulatory adjuvants, antibody responses were also
enhanced (d)
Technology and Patent Status
The opportunity
This technology is currently in prototype development and testing with
established antigens for proof of concept. We are seeking private and
public funding, as well as academic and industrial collaborations with
the view to out-license the technology for co-development and
commercialisation
The core technology of this is the targeting of antigens and particulate adjuvants to M cells
and antigen-presenting cells following mucosal immunisation. A number of patents have
been filed on this technology
Pharmaceutical formulations and ligands for use therein; mimetics for UEA-1. Inventors
Houghten, Richard, Pinilla, Clemencia, Lambkin, Imelda, O'Mahony, Daniel, Hamashin,
Christa, Schink, Amy, Osthues-Spindler, Lisa. Patent 7166296 Issued on January 23,
2007. Estimated Expiration Date: July 2, 2022.
A US provisional patent application [US61/485,653] has been filed earlier this year entitled
‘PLANT LECTINS TO TARGET LEUKOCYTES’. The application was filed jointly with
Trinity College Dublin and Merrion Pharmaceuticals, where the named inventors are; Ed
Lavelle, Edel McNeela, Darren Thomas Ruane, Christopher Davitt & Karen Misstear.
Researcher: Dr. Ed Lavelle, Dr. Karen Misstear & Merrion Pharmaceuticals
[email protected]
+ 353 1 896 2488
Contact: TTO Case Manager
[email protected]
+ 353 1 896 4152