Summary: Combining a tetanus vaccine with a virus particle may prove effective as a protection against Alzheimer’s. The vaccine could also be used to treat allergies and psoriasis, researchers report.
Source: University of Dundee.
Research from the Universities of Dundee and Oxford has shown how combining the tetanus vaccine with a viral particle that normally affects cucumbers can be used to treat psoriasis and allergies, and may even protect against Alzheimer’s disease.
Scientists led by Dundee’s Dr John Foerster and Oxford’s Professor Martin Bachmann, were able to take the protein coat of cucumber mosaic virus and incorporate a tetanus vaccine-derived protein structure known to stimulate the immune system in order to create vaccines to treat multiple chronic diseases.
The vaccine showed positive results in models of psoriasis and cat allergy and was shown to raise antibody levels thought to be beneficial in Alzheimer’s disease. These vaccines can be either preventative, which is the hope for Alzheimer’s but also therapeutic, meaning they can cure a disease like psoriasis after it has already been established.
More research is required to test the efficacy of the therapeutic in a clinical setting, but the Dundee-Oxford study raises the possibility of hundreds of thousands of people being spared the ravages of chronic diseases.
Dr Foerster said, “As an academic dermatologist with special interest in the immune system, my specific attention is on vaccines to be developed against chronic skin diseases. The idea is pretty simple – for diseases such as psoriasis or eczema, the newest and most effective medicines on the market are so-called ‘antibodies’, which are what you and I produce against bugs in a common cold.
“For chronic diseases, these antibodies are specially made against one of the body’s own proteins. By blocking that single protein, the disease gets better. To use the example of psoriasis, a protein called Interleukin 17 needs to be active for the disease to progress. By creating a vaccine that stimulates the body to make antibodies against Interleukin 17 itself we can replace the need for frequent and expensive injections and make this type of treatment much more affordable and accessible to patients who could otherwise not afford specially made antibodies.
“Our research shows that this technique works in mice and, importantly, our new vaccine technology shows that it is likely to be a more effective type of vaccine than existing ones in older people. Since many patients with chronic conditions like psoriasis are elderly this technology may work much better to obtain effective vaccines.”
The paper is published today in the journal Nature Vaccines. The researchers are now looking to begin clinical testing of the vaccine and have already received regulatory approval to initiate testing in humans. Present antibodies for psoriasis treatment typically need to be injected at least once a month to keep working, and cost around £10,000 per patient annually. A vaccine would offer much more affordable treatment.
In Alzheimer’s, it is known that a protein called beta amyloid can cause brain damage resulting in inhibited function. Previous unsuccessful trials saw patients injected directly with antibodies against the same target but the new research suggests that starting the treatment – in the form of prophylactic vaccines – could provide a way of offering treatment even before the disease becomes clinically apparent. It is possible such prophylactic approach may work better and this could not be done using frequent antibody injections.
Professor Bachmann, Professor of Vaccinology at the Jenner Institute in Oxford, said, “Alzheimer`s disease usually develops in elderly people. The fact that the vaccine described here is optimised for old individuals seems therefore particularly helpful. An additional important aspect of the current work is that we developed a platform technology and are currently broadening our preclinical studies to vaccines against Parkinson`s disease as well as chronic pain.”
Source: Grant Hill – University of Dundee
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer’s and cat allergy” by Andris Zeltins, Jonathan West, Franziska Zabel, Aadil El Turabi, Ina Balke, Stefanie Haas, Melanie Maudrich, Federico Storni, Paul Engeroff, Gary T. Jennings, Abhay Kotecha, David I Stuart, John Foerster & Martin F. Bachmann in Nature Vaccines. Published online October 23 2017 doi:10.1038/s41541-017-0030-8
Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer’s and cat allergy
Monoclonal antibodies are widely used to treat non-infectious conditions but are costly. Vaccines could offer a cost-effective alternative but have been limited by sub-optimal T-cell stimulation and/or weak vaccine responses in recipients, for example, in elderly patients. We have previously shown that the repetitive structure of virus-like-particles (VLPs) can effectively bypass self-tolerance in therapeutic vaccines. Their efficacy could be increased even further by the incorporation of an epitope stimulating T cell help. However, the self-assembly and stability of VLPs from envelope monomer proteins is sensitive to geometry, rendering the incorporation of foreign epitopes difficult. We here show that it is possible to engineer VLPs derived from a non human-pathogenic plant virus to incorporate a powerful T-cell-stimulatory epitope derived from Tetanus toxoid. These VLPs (termed CMVTT) retain self-assembly as well as long-term stability. Since Th cell memory to Tetanus is near universal in humans, CMVTT-based vaccines can deliver robust antibody-responses even under limiting conditions. By way of proof of concept, we tested a range of such vaccines against chronic inflammatory conditions (model: psoriasis, antigen: interleukin-17), neurodegenerative (Alzheimer’s, β-amyloid), and allergic disease (cat allergy, Fel-d1), respectively. Vaccine responses were uniformly strong, selective, efficient in vivo, observed even in old mice, and employing low vaccine doses. In addition, randomly ascertained human blood cells were reactive to CMVTT-VLPs, confirming recognition of the incorporated Tetanus epitope. The CMVTT-VLP platform is adaptable to almost any antigen and its features and performance are ideally suited for the design of vaccines delivering enhanced responsiveness in aging populations.
“Incorporation of tetanus-epitope into virus-like particles achieves vaccine responses even in older recipients in models of psoriasis, Alzheimer’s and cat allergy” by Andris Zeltins, Jonathan West, Franziska Zabel, Aadil El Turabi, Ina Balke, Stefanie Haas, Melanie Maudrich, Federico Storni, Paul Engeroff, Gary T. Jennings, Abhay Kotecha, David I Stuart, John Foerster & Martin F. Bachmann in Nature Vaccines. Published online October 23 2017 doi:10.1038/s41541-017-0030-8