Cell culture

Another technique is use of cell cultures to grow vaccine strains; such as genetically engineering baculovirus to express a gene that encodes an influenza coat protein such as hemagglutinin or neuraminidase. "A recent NIAID-supported Phase II clinical trial of a vaccine produced by Protein Sciences Corporation using this strategy showed that it is well tolerated and immunogenic; the company is conducting further clinical evaluation of this product. Other new pathways for producing influenza vaccines include DNA-based approaches and the development of broadly protective vaccines based on influenza virus proteins that are shared by multiple strains." AVI Bio Pharma Inc. has evidence of inhibition of multiple subtypes of influenza A virus in cell culture with Morpholino oligomers from the results of their labs and four independent research laboratories. "The key finding here is that our NEUGENE(R) therapeutics continue to show efficacy against all strains of influenza A, including H5N1." Morpholinos conjugated with cell penetrating peptides have been shown effective in protecting mice from influenza A."Several companies are focusing on new vehicles for growing antigens, which are the bits of a virus or bacterium needed to spur a person's immune system to fight an infection. VaxInnate, a New Jersey-based biotechnology company, has reported success using E. coli bacteria, which can cause a sometimes-fatal infection but also can be used to grow vaccine ingredients when the harmful part of the bacterium is removed. Dowpharma, a unit of Dow Chemical, has been using different bacteria found in soil and water, P. fluorescens, which may make a higher volume of antigens more quickly than E. coli."A recent study has shown promise by a vaccine called FluBlOk, which is made in insect cells. This experimental vaccine, which focuses on hemagglutinin, would cut the production process by one to two months, as well as avoiding other pitfalls of chicken eggs."The Committee for Medicinal Products for Human Use (CHMP), which reviews applications for 27 EU countries, found that Novartis's Optaflu vaccine, given to more than 3,400 people during clinical studies, met the CHMP's immunogenicity criteria [...] Novartis has said that Optaflu is a subunit vaccine, meaning it contains individual viral proteins rather than whole virus particles. [...] Novartis said it anticipates applying for US licensing of its cell-based flu vaccine in 2008. The company has conducted phase 1 and 2 clinical trials of the vaccine in the United States and in July 2006 announced it would build a $600 million plant in Holly Springs, N.C., to make cell-culture flu vaccines. In May 2006 the US Department of Health and Human Services awarded Novartis a $220 million contract to develop cell-based flu vaccines, and Novartis has said the money would go toward the cost of the new facility. Depending on when its vaccine is approved by the Food and Drug Administration, the plant could begin production as early as 2011 and be ready for full production as early as 2012, with an annual output of 50 million doses of a trivalent vaccine, the company has said. In the event of a flu pandemic, the facility is designed to have the capacity to make up to 150 million monovalent (single strain) doses each year within 6 months of a pandemic declaration, Novartis said. Novartis' other cell-based vaccine production facility is in Marburg, Germany.