When the US company, which is developing needle-free vaccine patches for the delivery of both antigens and immune-boosting adjuvants in influenza, pandemic flu and travellers' diarrhoea, launched its Phase I programme for the novel flu vaccine last November, it said the product could be on the market within three to four years.

Announcing interim results from the 353-patient study last week, however, Iomai conceded that it would now have to try a different antigen approach. The company said it was already working "actively" on alternatives to the split-virus antigens used in the Phase I trial, including a whole-virus approach that looked "extremely promising" in preclinical studies.

As Iomai's chief scientific officer Dr Gregory Glenn noted in a conference call to discuss the Phase I results, whole-virus antigens are highly immunogenic and are also difficult to inject, strengthening the rationale for a needle-free approach.

The company is also looking at other antigen technologies, such as viricide particles. Some of these alternatives could be sourced in-house, while others - notably, whole-virus antigens - would call for partnership with a supplier.

Iomai's transcutaneous immunisation (TCI) technology uses a patch placed on the surface of the skin to deliver vaccines and adjuvants to a group of antigen-presenting cells called Langerhans, located on the outer layer of the skin. These in turn deliver the vaccine and/or adjuvant to the nearby lymph nodes, producing a sustained immune response.

The company could not supply any quantitative data from the Phase I trial, which evaluated the safety and immunogenicity of Iomai's vaccine patch versus an injected intramuscular vaccine, both of them containing the same three flu antigens. The study is still ongoing and it will take another few months to collate safety data, pointed out president and chief executive officer Stanley Erck.

Four different dose levels were used (high, medium, low and no antigen) and the patch was worn for 18-24 hours. While seroconversion and seroprotection markers showed a superior immune response to the injectable vaccine, in other respects the interim results gave cause for optimism. The vaccine patch stimulated an immune response to each of the three antigens, and in a dose-dependent manner. It was well-tolerated at all dose levels, consistent with safety data from other studies.

Moreover, the Phase I trial also demonstrated that adding Iomai's immune-boosting adjuvant, LT, to the influenza antigens improved the immune response to the patch vaccine. This included "extremely robust" data on anti-LT titres, Glenn noted.

These findings provided "critical proof" that TCI could deliver large, complex antigens to immune systems, Erck commented. Iomai has left its financial guidance for the year untouched and continues to believe that "vaccination with a patch will be highly desirable to both patients and healthcare providers."

Nonetheless, the aim had been to show equivalence to the injectable vaccine, which is why Iomai will no longer be pursuing development of its patch with the triple-antigen formulation. While this split-virus approach is traditionally used for injectable flu vaccines - whole-virus vaccines are generally acknowledged to provoke a stronger immune response but are also more prone to side-effects - it may not be best suited for patch applications, the company suggested.

The split virus was an "old technology" that produced a "very heterogeneous mixture of materials," Glenn told the telephone conference. This heterogeneity was probably to blame for the sub-optimal delivery of the patch vaccine compared with the conventional injectable version, he said.

Iomai is already talking to "multiple" potential partners for its influenza vaccine programme, including Solvay, the company that supplied the split-virus antigens for the Phase I trials. The US company will now move these discussions forward based on the interim results just reported and its decision to take a different antigen track.

If it decides to proceed with a whole-virus antigen, Iomai should have no problem finding a supplier. All of the large manufacturers of flu vaccines use whole virus as a starting point for split-antigen products, the company pointed out.