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A novel vaccine strategy for asthma
While vaccines are available for protection against many infections, there
are still many bacterial and viral diseases for which no effective vaccine
currently exists.
Sir Charles Hercus Health Research Fellow, Dr Ian Hermans, is conducting
research into improving the potency of vaccines, believing that not only is
there a need to make successful vaccines for global threats like HIV, malaria
and tuberculosis, but that appropriately designed vaccines may be used in
the future as effective therapies for a number of common disease
conditions.
“There is accumulating evidence that vaccines can be used therapeutically
to treat conditions like cancer, allergy and autoimmune disease. For all
of these applications, it is critical that vaccines are designed to stimulate
immune responses of the correct ‘character’,” Dr Hermans says.
“For example, a vaccine for treating asthma will need to stimulate quite a
different immune response from a vaccine designed to treat cancer.”
Dr Hermans is carrying out his research programme at the Malaghan
Institute of Medical Research in Wellington. His team is currently
investigating a series of lipid-based compounds that activate a subset of
regulatory immune cells called iNKT cells, as these cells can significantly
enhance vaccine-induced immune responses.
Dr Hermans believes that iNKT cells can influence not only the size, but
also character, of vaccine induced immune responses. When iNKT cells
encounter specific lipids, they respond by releasing many soluble factors
that influence the behaviour of other immune cells.
“Immune responses are often described by immunologists as Th1 (“Thelper 1”) or Th2 depending on the types of soluble factors the immune
cells release. However, iNKT cells release factors of both Th1 and Th2
profiles, so we are now concentrating on specifically biasing this response
in one way or the other,” Dr Hermans says.
Immune responses to intracellular pathogens typically involve T cells
making Interferon-g and B cells producing antibodies of an IgG2a subclass.
These responses are described as “T helper 1 (Th1)’ biased responses.
Responses to parasites, on the other hand, typically involve T cells making
Interleukin 4, with B cells producing antibodies of an IgG1 and IgE
subclasses. These responses are described as “Th2’ biased responses
Dr Hermans is focusing on asthma because it arises from an inappropriate
immune response.
“It is essentially an unwanted Th2 response to a pollen or environmental
particle. There is some evidence that the symptoms of asthma can be relieved
by ‘deviating’ the immune response from a Th2 to a Th1 response. We are
therefore investigating whether vaccines that introduce a ‘Th1 character’ to
the immune response can be useful. This will be achieved by utilising lipid
adjuvants that stimulate the activity of NKT cells, “Dr Hermans explains.
By investigating adjuvants that bias immune responses, Dr Hermans
believes it may be possible to improve vaccines to treat a variety of diseases.
Cancer therapy is also a key area for the team, with the Malaghan Institute
and Wellington Hospital working in collaboration with Queensland Institute
of Medical Research on a phase III trial of vaccine-based ‘immunotherapy’
in melanoma patients.
This research is funded by the Health Research Council of New Zealand.
HRC66 2006
Level 3, 110 Stanley Street, Auckland PO Box 5541,
Wellesley Street, Auckland, NZ
Telephone 64 9 303 5200 Facsimile 64 9 377 9988
Website www.hrc.govt.nz
Health Research Council of New Zealand
Te Kaunihera Rangahau Hauora o Aotearoa
Dr Ian Hermans
Key words:
– immune responses,
immunotherapy, vaccines.
Key facts:
– asthma is one of the most common
chronic diseases affecting New
Zealand children and adults
– the economic burden of asthma in
New Zealand is estimated to be
$800 million per annum
– there are still many dangerous
parasitic, bacterial and viral
diseases for which there are no
effective vaccines. These include
tuberculosis, HIV/AIDS and
malaria.
Aims of this research:
– to increase the potency of vaccines
– to ensure immune responses
generated to a vaccine are
appropriate to the disease being
treated.
What this research has found:
– there is strong evidence that lipids
that stimulate iNKT cells can be
used to significantly enhance
vaccine-induced
immune responses.