The UK biopharmaceutical company is working on the project with researchers from the University of Cambridge and the Royal Holloway University of London, under the direction of Professors Nigel Slater and Simon Cutting.

Cobra's proprietary ORT-VAC oral vaccine delivery system comprises a gene-based oral attenuated bacterial vaccine strain that targets antigen-presenting cells in the gut to induce mucosal and systemic immunity. The strain is generated by cloning genes that encode antigens into ORT (Operator-Repressor Titration) plasmids and expressing them in attenuated bacteria.

The technology is a quick and straightforward way of constructing bacterial vaccine strains that can express "massive" quantities of antigenic proteins, the company says. The ORT-VAC system also has potential as disease therapy (e.g., in cancer, where the body's immune system would be harnessed) or as prophylaxis in disease prevention.

Needle-free delivery of vaccines enhances ease of distribution and administration as well as greatly simplifying production techniques, Cobra notes. These benefits make the ORT-VAC system particularly suitable for cost-effective vaccines needed in developing countries and for applications in the animal health sector.

Proof-of-principle studies with mice, published last year in the journal Vaccine, have already shown that the ORT-VAC system can achieve a high level of immunity after administration of a single oral dose of bacteria expressing a plague antigen.

A similar result was achieved with an anthrax antigen, noted Cobra's chief executive, David Thatcher. These experiments were conducted in conjunction with the UK Defence Science and Technology Laboratory in Porton Down.

The £1.1 million awarded by the DTI will largely support preclinical studies in the laboratories of Cobra's collaborators, the company said. The initial emphasis will be on developing an oral vaccine against avian influenza, Thatcher told in-PharmaTechnologist.com., as H5N1 antigens are "widely available with modern genetic engineering techniques".

Kickstarting an oral AIDS vaccine is more of a challenge, as "there isn't a vaccine in HIV that works", Thatcher commented. While Cobra has a number of HIV genes "in the fridge", it has yet to decide on a final approach, which will depend on discussions with collaborators in the run-up to the DTI funding being released later this year.

The company has been working on an AIDS vaccine for a number of years with partners including Oxford University, a research team in South Africa and GlaxoSmithKline (GSK) Biologicals.

The last of these collaborations was only recently dissolved. Cobra announced last month that GSK and a third partner, the International AIDS Vaccine Initiative (IAVI), had pulled out of the vaccine programme following "a GSK internal project review".

An agreement was signed with these partners in May 2006 for the process development and manufacture of two HIV vaccine candidates for evaluation in clinical trials. Cobra stressed that the decision by GSK and the IAVI not to pursue the project any further was "unrelated to the capabilities or the work undertaken by Cobra", all of the company's commitments in this respect "having been successfully achieved".

While the research undertaken with the UK's Ministry of Defence on potential oral vaccines against anthrax and plague has generated an "exciting and interesting" model for the proof-of-principle data needed to take the ORT-VAC concept forward, these applications are "commercially not that attractive", Thatcher commented.

The only real customer for anthrax and plague vaccines is the US government, and its commitment is qualified by an uncertain political climate, he noted. There are already a number of vaccines in development for anthrax, while plague can easily be treated with antibiotics, Thatcher added. Cobra is still involved in the project but the Ministry of Defence is "not hammering on our door", Thatcher said.

A further vaccine programme for (initially) malaria and tuberculosis, which uses as a delivery vehicle genetically engineered spores of the harmless gut bacterium Bacillus subtilis, is still in early development.

Cobra does not expect to see meaningful clinical data from this project, which is being pursued by a consortium of vaccine and immunology experts from around the world, for another six months or so, Thatcher told in-PharmaTechnologist.com.