The H1N1, swine flu vaccine, which will be offered to most people in the UK is pandemrix from GlaxoSmithKline. The viral antigen for this vaccine is grown in eggs and for those people who have an allergy to eggs or chicken protein, the alternative is the celvapan vaccine from Baxter International. Baxter has been involved in a few scandals over recent years. In 1996 haemophilia components were contaminated with HIV virus and injected into tens of thousands of people, including thousands of children. Even when the contamination became known, Baxter continued to release the contaminated clotting substance. As of March 2008, Baxter's heparin had been linked to hundreds of serious and sometimes life-threatening reactions, including at least 4 deaths.
In February 2009, Baxter released contaminated flu virus material from a plant in Orth-Donau, Austria.
The contaminated product, a mix of human H3N2 seasonal flu viruses and unlabelled avian H5N1 viruses, was supplied to an Austrian research company. The Austrian firm, Avir Green Hills Biotechnology, then sent portions of it to sub-contractors in the Czech Republic, Slovenia and Germany.
The contamination incident, which is being investigated by four European countries, came to light when the subcontractor in the Czech Republic inoculated ferrets with the material and they died. Ferrets shouldn’t die from exposure to human H3N2 flu viruses.The H5N1 component of the product was found to be live. The accidental release of a mix of live H5N1 and H3N2 viruses could have had dire consequences.
Celvapan H1N1 is the first cell-cultured and non-adjuvanted vaccine to be authorised by the European Commission, to be marketed within the European Union.
So, having a wee shuftie at the patients' information leaflet, produced by Baxter:
"What Celvapan contains
Whole virion influenza vaccine, inactivated, containing antigen of pandemic strain*:
A/California/07/2009 (H1N1) 7.5 micrograms** per 0.5 ml dose
* propagated in Vero cells (continuous cell line of mammalian origin)"
Vero cells are lineages of cells used in cell cultures. The lineage was developed in 1962 by two scientists at a university in Japan. The Vero lineage is continuous, which means it can be replicated through many cycles of division without becoming senescent (liable to the process of aging that normal cells go through). For this reason they are referred to as, "immortalised."
What is coming through that needle?
The problem of pathogenic vaccine contamination.Vero cells are susceptible to a broad range of viruses and are widely used to develop vaccines against associated diseases. The array of viruses that Vero cells are susceptible to is broad and includes polioviruses, simian virus 5 (SV5), simian virus 40 (SV40), rubeola, rubellavirus, reoviruses, simian adenoviruses, Getah, Ndumu, Pixuna, Ross River, Semliki Forest, Paramaribo, Kokobera, Modoc, Murutucu, Germiston, Guaroa, Pongola, and Tacaribe
Picking out SV40, simian virus 40, for special attention. This virus contaminated both the Inactivated Polio Vaccine, created by Dr Jonas Salk, and the Oral, or "Live," polio vaccine, created by Dr Albert Sabin. Although a Federal law was passed in the USA in 1961, requiring that no vaccine contained this virus, it did not require that seed material be discarded and it has been alleged that oral polio vaccine containing the virus was administered up to the 1990s.
SV40 is a persistent infection in Vero cells.
A letter from the FDA in 2001 to vaccine manufacturers said that use of immortalised cell lines was a cause for concern and that all product should be free of intact Vero cells. Yet, it seems that there are very basic safety questions not resolved by the manufacturers.
Cell replication/division: how SV40 can disrupt this process and cause cancer.
Cells of all multicellular organisms replicate during creation and maturation and for growth and repair of tissues. When cells are injured or damaged in this process, tumour-suppressor genes promote cell cycle arrest to stop these damaged cells proliferating out of control and forming tumours. P53 and retinoblastoma (Rb) are tumour-suppressor genes, which are inactivated by SV40, allowing damaged cells to proliferate.
SV40 is a type of polyoma virus: poly means many; oma means tumour. This designates its ability to form many types of tumour.
The celvapan patient infromation leaflet instructs that you should not receive celvapan if you have had a sudden, life-threatening allergic reaction to any of the ingredients or any substance of which there may be traces in the vaccine. One of those substances is formaldehyde, which is used to split and inactivate the influenza virus. Formaldehyde was also used in the injected form of polio vaccine used between 1955 and 1961, but this vaccine was contaminated with SV40.
SV40 - Polio vaccine contamination
Soon after its discovery, SV40 was identified in the injected form of the polio vaccine produced between 1955 and 1961. This is believed to be due to kidney cells from infected monkeys being used to amplify the vaccine virus during production. Both the Sabin vaccine (oral, live virus) and the Salk vaccine (injectable, killed virus) were affected; the technique used to inactivate the polio virus in the Salk vaccine, by means of formaldehyde, did not reliably kill SV40. (SV40 Foundation)
Finally, testing of the vaccine.
1) Safety: on a small number of healthy adult volunteers (10-12) to test safety of doses and to monitor for side-effects.
2) Safety and immune response: several hundred people in the age groups for whom the vaccine is intended. Often carried out in several different countries.
3) Safety, immune response and efficacy: first step towards its use in public health. Several thousand people tested in relevant age groups. If the vaccine passes all safety and efficacy requirements, the manufacturer can then apply for a licence to produce and distribute the vaccine.
4) Post-licencing evaluation. Ongoing surveillance to monitor for rare side-effects.
Testing of celvapan H1N1 vaccine:
Earlier this year, Baxter conducted tests with a "mock-up," vaccine, using a different strain. (Not H1N1) on several thousand people.
For celvapan H1N1, post-licencing, Baxter conducted randomized trials in 400 healthy adults, aged 18 and over and in 400 children and adolescents. Baxter said that once countries initiated vaccination programmes using celvapan, they would initiate a large-scale observational study of 9,000 people in different age groups.
So, instead of testing for safety and efficacy before the vaccine was distributed and administered, Baxter will carry out the most important phase of testing after countries have initiated vaccination programmes.
The guinea pigs for this vaccine will not be the usual volunteers who sign up for testing before use on the public. The guinea pigs will be those people queuing up to receive this vaccine, assuming that if the government has given its approval, it must be safe. And remember, because this is a vaccine introduced as a contingency in a pandemic situation, the vaccine manufacturers have immunity from liability.