Science - December 8, 2009

Virus produces better vaccine against Mexican Flu

The baculovirus can be used by companies to speed up the production of a better flu vaccine, including a vaccine for the Mexican Flu. This new vaccine is being developed in the United States. This is the proposal of Manon Cox who will receive her doctorate degree on 9 December in Wageningen.

Cox works in the American company Protein Sciences and has developed a flu vaccine this summer using the baculovirus. This vaccine can be produced in only one and a half months. Clinical studies in the United States have shown that it is effective in protecting people against the flu virus. She expects that the US government will approve the vaccine next year.  Afterwards, her company will begin the application for approval procedures in Europe.
Baculoviruses are special because they are genetically quite simple in structure, says Cox, and can be easily modified genetically. They can convert a certain group of insects - special caterpillar types - into complex proteins. When a piece of the flu virus genome is built into the baculovirus, it can manufacture anti-bodies against the flu virus.
The ability of the baculovirus to produce unusual proteins was discovered about 25 years ago at the Texas A&M University. The Wageningen professor Just Vlak, who will be Cox's examiner, was then a postdoc student there. Vlak is now the acclaimed authority in the area of baculoviruses.
The use of the virus to develop pharmaceutical products did not take place until very much later. 'Companies wishing to apply the technology would have to pay through the nose for the patents of Texas A&M', says Cox. Moreover, it was cheap to use hen eggs to produce the vaccines. Thirdly, the vaccine industry is very conservative, says Cox. With pandemics and shortage of vaccines looming up, this sector now faces pressure to improve vaccine development. The first vaccine based on baculoviruses has in the meantime been approved by the U.S. This is a vaccine against cervical cancer.
The first concept to produce a flu virus vaccine with baculoviruses dates from 1995. Cox, then employed by Gist-Brocades in Delft, has been working twelve years in this area. She spent most of this period on studies to prove that the baculovirus produced the needed vaccine, the vaccine really provided protection against flu in people, and that it caused no side effects. Approval of medicines in the United States is extremely strict.
To produce the vaccine, Protein Sciences breeds insect cells in a bioreactor. The addition of the baculovirus causes the cells to produce active proteins for the vaccine. These active proteins then need to be extracted from the mixture in the reactor and purified. The company has a current production capacity of five hundred litres. It has in the meantime received an American government subsidy of 145 million dollars to develop and propagate the technology.
The new flu vaccine gives better protection than the prevalent flu vaccine, claims Cox. 'We put in three times as much active ingredients in it than are found in the vaccine now used in the Netherlands.' In addition, the Dutch vaccine has an adjuvant ingredient to stimulate the immune system, says Cox. 'This ingredient hasn't been extensively tested yet. There are indications that the current vaccine causes an autoimmune disease in one out of a hundred children. If the vaccine produced with hen eggs were offered today for product registration, it would probably be rejected under the current strict approval procedures.'
Cox does not expect any problems in the approval of the new vaccine in Europe, where the rules are less strict than those in the U.S. However, her vaccine can be classified as a GMO in Europe, which could delay its approval.

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