Two interesting and very different technologies for vaccine delivery were presented by Mucosis and Hybrid Systems.
“We have developed a new way of formulating Lactococcus lactis into nonviable cells that can be loaded with antigens. We call these GEM (gram-positive enhancer matrix) particles, and when these are sprayed into the nose they raise protective immunity by activating the innate and adaptive immune system,” said Govert Schouten, Ph.D., CEO at Mucosis.
Using this platform, Mucosis has produced FluGEM™, an intranasal vaccine containing a range of flu antigens. Dr. Schouten presented preclinical data to show that of the 24 mice challenged with H3N2 flu virus, all 12 mice immunized with a FluGEM vaccine intranasally survived, while only two survived in the control group of 12 dosed with phosphate buffered saline.
“Needle-free intranasal application with this technology is possible and could be used to develop a universal flu vaccine,” Dr. Schouten stated. With FluGEM we are now moving into ferret models. We hope to begin Phase I trials soon.”
Hybrid Systems, on the other hand, offers a vaccine delivery system aimed at use with viral vectors. “We use polymers to coat viruses. This makes a stealth virus that can hide from the immune system so that it can deliver its DNA vaccine safely without being recognized and destroyed by antibodies,” explained John Beadle, M.D., executive chairman and CEO at Hybrid.
As proof of this, Dr. Beadle showed several examples where viruses coated with the polySTAR polymer used in small rodent studies appeared to evade the immune system and increase proliferation of T cells. In one, an Ad5 OVA with and without a coat polymer containing a lipid dipalmitoyl-S-glyceryl cysteine (Pam2Cys) were injected into mice. The mice produced double the number of CD8 T cells with the coated virus.
In another study, a vaccine consisting of recombinant vaccinia virus encoding the tumor-associated antigen carcinoembryonic antigen (CEA) was coated with the polymer and injected into mice. The number of CD4 cells was almost doubled in those mice injected with the coated virus and even in mice that had been preimmunized with vaccinia-CEA vaccine the CD4 response increased more than sixfold that of the uncoated virus.
“This process sounds complicated, but is very simple as you just have to co-incubate the polymer with the virus and the polymer will coat the virus according to size and charge density,” Dr. Beadle stated. “Therefore, this process could be carried out in a GMP environment. It can be used with any virus that does not have a friable envelope, so is applicable to MVA, AAV, Herpes, and Adeno viruses. We think its primary use will be to deliver prime and boost DNA vaccinations, but it could also be used to deliver gene therapy vectors.”
Where's the Profit?
With biotechs in the vanguard of developing some interesting platform technologies and even novel vaccines, some companies are taking their products all the way to market but they need to exercise caution when doing this. “When biotechs are developing vaccines, manufacturing is often the last thing on their mind, yet improving output is often the differentiator between making a good profit or very little return on a product,” warned Catarina Flyborg, leader of enterprise solutions at GE Healthcare.
To prove this point, Flyborg presented examples where using a range of ready-to use products such as bioreactors, pre-packed chromatography columns, and filters could significantly increase the number of doses, while reducing cost of goods.
According to Flyborg, 500 L Wave disposable bioreactors could be used to produce 18 batches of a trivalent flu vaccine. This would total six batches per strain producing four million doses and could be made in 90 days by applying ready-to-use systems, in a staggered production mode. She added that to produce the same number of doses using a traditional set up of stainless steel fermentors, repacking and cleaning chromatography columns, would take 96 days.
“Companies can apply ready-to-use technology and rapidly put together a facility that suits their needs. However, once you get past the 10,000 L scale using ready-to-use and disposable technology, the cost of goods becomes so high that this is not a workable option, so it really benefits small biotechs that don’t have existing capacity, or companies looking to quickly set up and produce batches in countries where they don’t have facilities.”
According to Dr. Klingan, in 1992 the vaccine market was worth €2 billion ($2.96 billion), €15 billion ($22.24 billion) in 2008, and could be worth €33 billion ($48.94 billion) by 2018. The clear way for big pharma to get a slice of this is to develop joint ventures and alliances and in some cases acquire biotech partners to gain technologies or market access. New vaccines require a complex mix of novel technologies and manufacturing capacity, as well as a balanced presence in different geographies if they are going to be sustainably profitable.