Flu vaccines are increasingly manufactured in cell lines that are actually or potentially oncogenic, and FDA guidelines allow high levels of contamination and no spot checks are carried out Dr. Sherri J Tenpenny
An electronic version of the full report can be downloaded from the ISIS online store. Download Now
Please circulate widely and repost, but you must give the URL of the original and preserve all the links back to articles on our website
Much concern has been generated over the new swine flu H1N1 vaccines that are being rushed to market. Clinical trials have been short – less than three weeks – and there is also the possibility of adding toxic oil-in-water adjuvants at the last minute to stretch the vaccine supply (see  Fast-tracked Swine Flu Vaccine under Fire, SiS 43). Those are not the only concerns. The new manufacturing process for flu shots, called cell-line technologies, are little understood and have the potential for serious, long term consequences.
Manufacturing the “regular,” annual flu shot
Each year, between January and March, an FDA advisory panel selects the three influenza strains expected to be in circulation during the upcoming flu season. Admitting that the process is an “educated guess,” the CDC sends the selected seed virus to the FDA for approval, and is then distributed to manufacturers for vaccine production.
The annual flu shot contains three viral strains: two type influenza A viruses and one type influenza B. Most commonly, two of the viruses are the same viruses included in the preceding year’s shot. The third virus is typically a new strain in circulation. This is the purported reason for giving the shot each year. The new strain is modified through a laboratory process called reassortment to ensure that it can readily grow in eggs. Once the modification is complete, all three viruses proceed through tricky manufacturing steps for what goes in that vial.
The cumbersome flu shot production process uses up to 500 000 fertilized chicken eggs per day for up to eight months. Hundreds of millions of fertilized eggs become “mini-incubators” for cultured viruses. When the chick embryos are 11-days old, the amniotic membrane (the egg white) is manually injected with a drop of viral-containing solution. Several days later, the gooey viral suspension is centrifuged to remove as much chicken blood and tissue from the solution as possible. Residual egg protein remains within the final vaccine solution and is the reason why persons with an egg allergy are advised against receiving the flu shot.
The entire process, from viral selection to viral harvest, can take up to nine months . With the potential for a pandemic and the Director General of the WHO, Margaret Chan, requesting up to 4.9 billion of flu shots to vaccinate the world , the slow lead time and labor-intensive production process cannot meet the demand for massive quantities of pandemic flu vaccine.
Enter cell line technology
Cell line technologies that use cells and animal tissues for growing viruses found in vaccines have been deployed since the 1950s. Examples include calf lymph for smallpox vaccines; African green monkey cells (AGMK cells) for polio vaccines and mouse brain cells for the Japanese encephalitis vaccine. In the 1960s, cells from aborted human fetal tissue, called MRC-5 and WI-38 cells, were developed and are still used for the manufacture of rubella chickenpox, hepatitis A and shingles vaccines.
Since the early 2000s, dozens of human and animal tissues have been investigated for use in viral vaccines, especially for the production of influenza shots. Batches of vaccine can be produced in less than six weeks instead of just one crop per year with eggs, thus ramping up production enormously. While many of the new cell lines are still considered experimental, cell line techniques have attracted all the major players in the vaccine and biotech industry.
Prior to 2007, cell lines were little used for flu shots, primarily for logistical reasons: Flu shots made from cells instead of eggs required a complete retooling of existing production facilities. None of the manufacturers were willing to invest the hundreds of millions of dollars and the five to seven years to construct new vaccine plants. But when the threat of the bird flu pandemic was hyped in 2006, the government opened its coffers and spilled billions of dollars into the pockets of the drug companies, giving them the capital to build new flu shot production facilities. By 2012, the first cell line factory will be completed in North Carolina. Vaccine giant Novartis will then have the capacity to produce 150 million flu shots per year, making it the world’s biggest commercial production plant for influenza vaccines and the adjuvant MF-59.
Cell cultures: the next frontier in vaccine production
Several cell lines are currently under investigation. Novartis’ EU-approved flu shot, Optaflu, was produced using a cell line called Madin-Darby (MDCK), cells extracted from the kidneys of a female cocker spaniel. Dutch giant, Solvay Pharmaceuticals, has been working with MDCK cells since the early 1990s.
Another independent company, Protein Sciences Corporation, has been working on a patented influenza vaccine produced from caterpillar eggs.This vaccine strategy, known commercially as FluBlok, isolates a purified concentration of (H) antigen on the surface of an influenza virus and inserts the antigen into a second virus called a baculovirus. The (H)-containing baculovirus is then inserted into insect cells growing in culture. Several clinical trials involving the bug-created vaccine have shown that the antigens elicit a strong antibody response in humans . The vaccine, no doubt, contains snips of insect DNA. This technology is being tested in Europe and is not yet approved for use in the US.
A third type of cell line, called PER.C6 cells, is derived from retinal cells of aborted fetal tissues. The fetal cells are transformed by infecting them with an adenovirus, turning them into “immortalized” cells and the capability to replicate endlessly. By their very nature, these cells are neoplastic (cancer-causing); researchers refer to them as “oncogenic” cells. If tumors are formed when the cells are injected into experimental animals, the cell lines are beyond oncogenic; they are tumorigenic.
A serious concern about whole, live PER.C6 cells is that they are capable of causing tumors when transplanted into the skin of mice. The FDA requires a filtration method to be used during vaccine production that is designed to removes all cells before the final product is packaged. Several studies have been conducted to assure vaccine developers that PER.C6 cells do not cause cancer and do not contain stray tumor causing viruses , but the risk remains for the cells to contaminate the final vaccine products.
There is a real risk of residual retinal DNA and stray viral fragments from the animal tissues getting into flu shots. DNA snips are classified as either “infectious” or “oncogenic” by researchers who worry that the stray DNA is being incorporated into the recipient’s DNA. FDA regulations insist on the “importance of minimizing the risk of oncogenesis in vaccine recipients”. But manufacturers have been instructed only to ensure the final vaccine contains less than 1 million residual animal cells and less than 10 ng stray DNA per vaccine .
Is every lot tested for purity in accordance to these parameters? No. Spot-checked lots are sent to the FDA, and the FDA takes the word of vaccine manufacturers that these standards have been met.
The risks of tumorigenic cells are known
Since 1998, the FDA and its subdivision, the Centers for Biological Evaluation and Research (CBER), have been drafting regulations to allow use of both oncogenic and tumorigenic cell lines to be used in vaccine production. The FDA is fully aware that the new cell lines, especially the PER.C6 cells, have substantial risks, including the risk of potentially deadly adventitious (stray) viruses making their way into shots.
For example, the FDA acknowledges that the SV 40 virus (simian virus 40 from monkey kidney cells) was in the early polio vaccines and its risks : “The experience in the early 1960s with SV40 contamination of poliovirus and adenovirus vaccines and the continuing questions regarding whether SV40 could be responsible for some human neoplasms [cancers] underscores the importance of keeping viral vaccines free of adventitious agents.
“This is particularly important when there is a theoretical potential for contamination of a vaccine with viruses that might be associated with neoplasia [cancer]…It is unclear whether cell substrates have a greater or lower risk [of contamination] than other types of cells However, if their growth in tissue culture is not well controlled, there may be additional opportunities for contamination…”
And it gets worse. The same FDA memo goes on to say : “In addition to the possibility of contamination of cell substrates with adventitious viruses…the use of immortalized, neoplastic human cells to develop [vaccines] raises theoretical concerns with regard to possible contamination with TSE/BSE agents.”
TSE is Transmissible Spongiform Encephalopathy, a condition that includes a group of rare degenerative brain disorders characterized by tiny holes in the brain tissues, giving a “spongy” appearance when viewed under a microscope. When this condition occurs in cows, it is called Bovine Spongiform Encephalopathy, commonly known as “mad cow disease.” In a study published in 2004, researchers found that any cell linecould potentially support the propagation of TSE agents .
Clearly, CBER is aware and disquieted over the carcinogenic potential of animal cells in vaccines because they require manufacturers to take “every available precautionary step” to eliminate the suspicious cells from the vaccine final product. The FDA also admits concerns about cancer-causing possibility from all types of cell lines. The question begging to be answered is, knowing the potential risks of using cell lines to create vaccines, why are cell line technologies allowed at all?
Dr Tenpenny Comment left 23rd May 2010 15:03:02 Novartis opened a new factory last fall in North Carolina that will produce flu shots in the future combining MDCK (dog kidney cells) and MF59 (squalene). The animal cell vaccines are not approved for use yet in the US but no doubt they will be soon. This is an article I wrote on Huffington Post about the celebration of Novartis. http://www.huffingtonpost.com/dr-sherri-tenpenny/novartis-is-celebrating-s_b_372551.html
tony villar Comment left 8th October 2009 10:10:07 swine flu is man made. Greed for the green bucks.
Theresa Matthews Comment left 9th October 2009 16:04:14 The cadaveric human growth hormone story/tragedy in the US has never made front page news here. The Louping illness vaccine which led to mass scrapie inocculation seems to have fallen far from public/scientific consciousness as well. These cell line techniques are being developed and fast forwarded in an era when the TSE's have proliferated faster than our understanding of them. We still have no effective ante-mortem screening test for human TSE's. If domestic cats were affected and the hounds never studied, why would anyone want a vaccine developed, wrapped up and delivered from such a high risk area? Especially when CJD diagnosis and reporting remains such a common complaint from victims groups world-wide. And further, with the 10 year lag in closure of our feed ban...the use of any mammal in this country for any biotech purpose poses just as much a concern. In fact the food chain has likely been so widely affected by CWD that a caterpillar might just be a problem now. Since the University of Wisconsin researchers report voles are a potential problem for the grain, maybe they could assess the risk here.
Ingrid Blank Comment left 7th October 2009 16:04:11 Novartis' OPTAFLU vaccine may also constitute a major scoop for the multi-billion dollar ARV-industry, since it may give false-positive results in serology tests using the ELISA method to detect antibodies against HIV-1, Hepatatis C and HTLV-1, which may be due to the IgM response to the vaccine.
Claudia Comment left 10th October 2009 07:07:35 There are many serious concerns raised in this article, especially since cell-line technology seems to be poised to replace the older vaccine production method using eggs.
That said, I kept seeing news articles saying the new swine flu vaccines are "made the same way" as previous seasonal flu vaccines. I sat down to research this, suspecting a public relations ploy. But what I found was an assertion that the FDA has NOT approved cell-line vaccines for the swine flu:
"While other...companies are working with different unapproved-as-yet technologies that can manufacture flu vaccines faster than the current traditional approach of growing them in chicken eggs, the FDA opted for the latter, age-old mechanism with its approvals today. Each of the selected companies use egg-based methods to produce their vaccine products."
They may be approved for other countries (non US) and they may also be approved later by the FDA. But as of last month, this is not a problem in the US.
Right-to-life groups have followed this issue very closely due to the fetal-cell PER.C6 cell line. They may be losing interest since it has been reported that this cell-line is being replaced by a "moral" one. Who then will pressure the FDA to do a rigourous job of safety testing?
Penny Rai Comment left 15th October 2010 19:07:14 My question now would be then, Is the annual flu shots necessary at all? With all these concerns mentioned, I don't think I would continue giving my kids the annual flu shots.
Isaias Valencia Comment left 9th February 2011 15:03:15 They say that because it is common for people undergoing cancer treatment to have a compromised immune system, the flu shot is recommended for most. The flu can lead to more serious conditions like pneumonia, which can be life-threatening to those with a weakened immune system. This is all non-sense information that they implant in our brains. Source: Electronic Cigarette
Angry Birds Comment left 16th July 2011 15:03:29 They say that because it is common for people undergoing cancer treatment to have a compromised immune system, the flu shot is recommended for most. The flu can lead to more serious conditions like pneumonia, which can be life-threatening to those with a weakened immune system. This is all non-sense information that they implant in our brains. http://playangrybirdsonlinefree.com
V w Comment left 2nd October 2012 20:08:38 Medicine has gone completely mad.read for yourself.
FDA Vaccines and Related Biological Products Advisory Committee Meeting September 19, 2012
Here is a brief summary
"Three cell lines derived from human tumors will be discussed during the September 2012 VRBPAC meeting: the CEM leukemia T cell line, the A549 lung adenocarcinoma cell line, and the HeLa cervical carcinoma cell line. These cell lines serve as the basis for this discussion because sponsors have proposed their use in the production of vaccines for evaluation in clinical trials. CBER requests that these cells be viewed as representative of this type of cell substrate so that the recommendations of the advisory committee will be applicable to other tumor-derived cell lines (human and non-human) proposed for vaccine manufacture in the future."
"In previous discussions regarding the possible use of tumorigenic cell lines for vaccine manufacture, three major safety concerns were identified that needed to be addressed: 1) the presence of residual live cells in the vaccine that might have the potential of being tumorigenic in humans; 2) the presence of residual DNA from the cell substrate; and 3) the potential presence of adventitious agents, including adventitious viruses,( ie contaminating viruses) that might have contributed to the tumorigenic phenotype. The current data suggest that these are also the major issues associated with tumor-derived cells, including cell lines derived from human tumors.
peter Comment left 6th January 2013 04:04:29 Thanks for the facts. It's refreshing to read an article that is free from hype and supported by the research conducted by the organizations it opposes.
Ann Pagbourne Comment left 30th March 2015 17:05:04 I had the a flu vaccination in early 2011, the vaccination site never healed and was eventually excised and found to be pre-cancerous.
A few months ago I had the new vaccine to prevent pneumonia, and once again the site has not healed and is slightly sore and flaky, i have not yet consulted my GP.