Abstract Book 2010 - CIMT Annual Meeting

110 Femel | Enhancing immunity & adjuvants
Identification of a potent, non-toxic adjuvant
for use in therapeutic vaccines
Julia Femel 1 , Elisabeth JM Huijbers 1 , Maria Ringvall 1 , Lars Hellman 2 , Anna-Karin Olsson 1
1 Department of Medical Biochemistry and Microbiology, Uppsala University, BMC, SE-75123 Uppsala, Sweden
2 Department of Cell and Molecular Biology, Uppsala University, BMC, SE-75124 Uppsala, Sweden
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Monoclonal antibody-based therapies have made an
important contribution to current treatment strategies
for cancer and autoimmune disease. However,
their cost-intensive production could possibly lead
to limited availability of the therapy. Therefore obtaining
antibodies produced by the body through
therapeutic vaccination is an interesting alternative,
due to the low amount of required recombinant
protein. To circumvent the tolerance of the
immune system against self-antigens, an efficient
vaccination technology as well as a potent adjuvant
is required. The lack of potent, but at the same time
non-toxic and biodegradable adjuvants that can be
used in the clinic, has been a major limiting factor
for the development of therapeutic vaccines.
We have identified the biodegradable squalenebased
Montanide ISA720 combined with phosphorothioate
stabilized CpG oligo 1826 (Montanide/
CpG 1826) as an adjuvant able to break tolerance
against a self-molecule. A therapeutic vaccine
against tumor angiogenesis has been developed in
our group. This vaccine successfully breaks selftolerance
against the extra-domain B (ED-B) of fibronectin
using Freund’s adjuvant and the recombinant
protein Trx-EDB (see poster by Elisabeth
Huijbers et al.). To compare the immunostimulatory
properties of Freund’s adjuvant and Montanide/CpG
1826, we have vaccinated two groups of
C57BL/6 mice with Trx-EDB in combination with
either Montanide/CpG 1826 or Freund’s adjuvant.
Blood samples were collected regularly and analy-
zed for anti-ED-B antibodies.
Comparing the ability of Montanide/CpG 1826 and
Freund’s adjuvant to stimulate an antibody response
against the extra-domain B of fibronectin revealed
that Montanide/CpG 1826 induced higher anti-ED-
B antibody titers, as well as less variation between
individual animals, than Freund’s. Furthermore
antibodies in animals treated with Montanide/
CpG 1826 were still detectable after eleven months,
while antibodies in mice treated with Freund’s adjuvant
had returned to base levels at this time point.
Analysis of the IgG isotypes showed that IgG1 and
IgG2b were the main isotypes in both treatment
groups. However, preliminary data indicate that
Montanide/CpG 1826 might have the capability to
induce antibodies with higher affinity to ED-B than
antibodies induced with Freund’s adjuvant.
With Montanide/CpG 1826 we have identified a
non-toxic alternative to Freund's adjuvant, which
is at least as potent with respect to inducing an
immune response against a self-antigen. This will
facilitate introduction of therapeutic vaccines to the
clinic.