Caterpillar cells to churn out flu vaccine
potential money-saver for pharma firms, and has proved just as
effective as vaccines produced using conventional egg-based
techniques.
Research published today in the Journal of the American Medical Association (JAMA) reports findings from a study involving a flu vaccine that relies on a virus that usually infects insects (known as baculovirus) to pump out the main components of the flu virus in a cell line drawn from caterpillars. Traditional vaccine production has involved cultivating flu virus in fertilised eggs, with each egg tending to yield less than a teaspoonful of material that will end up as part of the vaccine. According to the researchers, by removing eggs from the vaccine production process and using the insect cell approach instead, manufacturers could make significant savings in time (and consequently cost) and increase productivity as a result. "It's typically a six-month process to produce enough flu vaccine to protect the public," said lead researcher John Treanor of the University of Rochester in the US. "Taking eggs out of the process would likely slice one or two months off the production process, [which] would allow manufacturers to ramp up vaccine production more quickly than if they had to wait for the production of millions of eggs." The vaccine the researchers used is produced by US biopharmaceutical firm Protein Sciences under the name FlubIØk. Using recombinant DNA techniques, the company focused on the haemagglutinin portion of the flu virus, with the vaccine itself consisting of three recombinant haemagglutinin proteins from flu strains selected by the World Health Organization and the Center for Disease Control as the biggest threats during winter 2004-5. The baculovirus expression technique is also championed by the company, possessing several advantages over other expression techniques in terms of speed (taking weeks rather than months to produce high levels of protein), cost, glycosylation, and folding. The technique itself involves injecting genetically engineered baculoviruses into bioreactors containing proprietary insect cells. The modified baculoviruses then infect the cells, causing them to produce the desired protein. After several days in a nutrient rich environment, the cells are harvested and the protein extracted and purified. Unlike other conventional vaccines, the FlubIØk vaccine does not contain neuraminidase, an enzyme that allows a flu virus to replicate and spread. It had previously been thought that the neuraminidase component of vaccines may be important for protection in situations where there is not a close antigenic match in the haemagglutinin. However, the study reported today suggests that this may not be the case, with a pure haemagglutinin vaccine generating a substantial amount of protection in the sample study. The researchers carried out a study involving two different doses of the vaccine (one at 75 micrograms and the other 135 micrograms) and a placebo shot. Subjects were then monitored over the following months and, according to the report published today, the two vaccines reduced flu infection rate by 86 per cent, supporting claims that it is just as effective as traditionally manufactured flu vaccines. The speed with which genes can be cloned and inserted into recombinant baculoviruses makes this expression technology particularly well suited for the production of flu vaccines, as it means that the vaccine can be updated at regular intervals to tackle the latest strains. The researchers also note that the "extraordinarily high" yields of protein that are possible using the system provide the opportunity to use much higher and potentially more effective doses of vaccine. This could prove especially useful in terms of pandemic preparedness and protecting against the threat of avian flu, which has been shown to require much higher doses of vaccine to achieve a sufficient level of protection. Any technology that helps increase vaccine production, particularly if it also confers time and cost benefits, is likely to seized upon by the pharmaceutical industry, particularly in this time of heightened awareness regarding the risk of pandemics and avian flu. Less than two months ago the World Health Organization (WHO) again voiced its concerns about the ability of the global community to produce enough vaccine to protect populations in the event of a pandemic. With current vaccine demand at around 300 million doses per year, and global production capacity at less than 400 million doses, the industry seems to only just be keeping its head above water as it is. According to the WHO, if a pandemic were to strike, demand for vaccines would rocket to 20 times its current level, causing a public health, manufacturing and logistical nightmare. With the use of cell culture systems for vaccine production becoming increasingly popular and the insect cell line used in today's study already being used to produce a vaccine against human papilloma virus, the research presents a promising option for vaccine manufacturers in the fight against the threat of a flu pandemic.
