A serious safety issue that should not be swept under the regulatory carpet. Professor Joe Cummins
When the Human Papilloma Virus (HPV) vaccine Gardasil was recently found to be contaminated with DNA, the US Food and Drug Administration (FDA) lost no time in declaring that the DNA was not a contaminant but a harmless by-product of vaccine production. I disagree; that extraneous DNA is potentially harmful. It should also be noted that the safety and efficacy of HPV vaccines have been controversial from the start (see [1] The HPV Vaccine Controversy and other articles in the series, SiS 41).
HPV establishes productive infections only in keratinocytes of the skin or mucous membranes. While the majority of the known HPV types cause no symptoms in most people, some types can cause warts (verrucae), while others can lead to cancers of the cervix, vulva, vagina, penis, oropharynx and anus.
Recently, HPV has been linked to an increased risk of cardiovascular disease. In addition, HPV 16 and 18 infections are strongly associated with an increased risk of developing throat cancer. Worldwide in 2002, an estimated 561 200 new cancer cases (5.2 %) were attributable to HPV, making HPV one of the most important infectious causes of cancer, and cervical cancer is the second most common cancer in women worldwide. In 2008, there were an estimated 529 000 new cases of cervical cancer and 274 000 deaths; more than 85 % of the deaths in developing countries, where it accounts for 13 % of all female cancers [2].
The HPV genome consists of 8 genes coding for proteins and a non-protein-coding region with regulatory genes. The genes are distinguished as early and late functioning in virus development. The early genes include those involved in virus replication and transcription along with the oncogenes for cancer development. The late genes encode the two structural proteins L1 and L2 of the virus capsid. HPV infects the basal cells of the cervical epithelium when it is damaged in some way. The viral genome becomes established in the basal cells as an episome (an independently replicating nuclear micro-chromosome). The episome replicates in tandem with the chromosomes of the cell and forms virus particles. The complete virus particles are in the outermost cells of the epithelium and the viruses are spread as the cells slough off from the epithelium. Some virus proteins function as oncoproteins, transforming the epithelial cells to a precancerous state. HPV infection is necessary but not sufficient for cancer formation, however. In high grade lesions and cancer, an episome is integrated into the cell chromosome. Integration disrupts a viral transcription regulatory protein that controls the production of the cancer proteins, leading to their continual and enhanced production [3] (Recombinant Cervical Cancer Vaccines, SiS 29). HPV integration into human chromosomes is non-random; with integration hot spots in chromosome regions homologous to the oncogene E5 of HPV or the structural protein L2 [4]. Women with cervical cancer have been found with viral chromosomes integrated completely or partially as chromosome fragments, or as independent episomes. Partially integrated HPV was most prevalent in women with cancer while complete virus integration was about half as frequent and the episomal form rare. The cancer- causing integration breaks the HPV chromosome at the E1/E2 region, causing a loss of that region. This in turn results in loss of control of the cancer genes E6 and E7. The E7 cancer gene produces a protein that inactivates the retinoblastoma gene – a cancer suppressor gene - of the host cell, thereby promoting cancer [5]. (Retinoblastoma is an inherited cancer of the eye caused by loss of the retinoblastoma gene.) The main lesson is that fragmentation or breakage of the HPV DNA is an important factor in cancer progression of the host cell.
The viral genes have a complex transcription pattern. There is a single promoter for all of the early genes. The early promoter initiates production of a large pre-messenger RNA from which messages containing exons and introns are then spliced to generate each of the early proteins. The other viral promoter initiates production of pre-messenger for structural proteins L1 and L2, which also contain exons and introns, and are similarly spliced prior to translation of the messenger RNA into protein. There are early and late polyadenylation (poly A) signals for the large pre-messenger RNA transcripts. Gene expression of HPV is tightly coupled to the developmental status of the host cells [6].
Micro RNAs are very small (around 22 nucleotides in chains) non-coding regulatory gene products of cells. Micro RNAs are altered in a number of human cancers and one is significantly elevated in HPV anal cancer [7]. A cluster of micro RNAs was found associated with HPV head and neck cancers [8]. The natural history of HPV cancers shows a complex pattern of gene transcription and micro RNAs are implicated in the development of HPV cancers.
HPV vaccines have been deployed worldwide since 2006. Two vaccines have been commercialized: Gardasil, manufactured by Merck and Cervarix, manufactured by GlaxoSmithKline. They are prophylactic, that is, they prevent cervical cancer but do not cure existing infections, and are based on the L1 virus-like particles to achieve immunity against HPV. The L1 protein is capable of self-assembly to form empty virus like particles that activate the human immune system to form antibodies. The HPVs targeted by the vaccines are “high risk” types 16 and 18 and “low risk” types 6 and 11. The two commercial HPV vaccines are both made using genetically modified (GM) microbes in a laboratory. Gardasil protects against all four HPV types because it contains virus like particles with mixtures of the four subunit proteins, and is called a tetravalent vaccine. The four L1 proteins are manufactured using GM baker’s yeast. Cervarix protects against the HPV types 16 and 18, and is a bivalent vaccine, and is manufactured using GM baculovirus (a soil-born insect virus) in cultured insect cells [9].
The vaccine consists of the four Monovalent Bulk Adsorbed Products (MBAPs), one for each of the four human papillomavirus (HPV) types. The active components in each MBAP are virus-like particles (VLPs) made up of the recombinant major capsid (L1) protein for that HPV type, produced in recombinant S. cerevisiae. The pGAL110 yeast expression vector was used for all four HPVL1 proteins. The L1 genes were derived by a direct cloning protocol. However, the coding sequence for HPV11L1 was synthetically rebuilt based on HPV6L1 nucleotide sequences that supported good VLP expression in yeast. Polymerase chain reaction (PCR) was used to subclone the L1 genes into the yeast expression vector pGAL110, which contains the yeast GAL1-GAL10 promoter and the yeast ADH1 terminator (ADH1t) for transcription termination and polyadenylation. The pGAL110-related yeast expression vectors for each of the four HPV types were used to transform the recombinant S. cerevisiae [10].
In 2011, Gardasil was found to be contaminated with recombinant HPV DNA in all of the lots of vaccine marketed in the United States, Australia, New Zealand, Spain, France and Poland. One of the DNA fragments identified was a gene fragment from the HPV capsid protein L1 [11]. Sane Vax, a girl age 13, was found to have blood containing HPV DNA two years after Gardasil inoculation [12]. Other DNA contaminants were not specifically identified in the many contaminated vaccine samples but are presumably DNA fragments from the genetically modified yeast used to produce the vaccine protein. Even though the FDA and the vaccine manufacturer had earlier claimed that Gardasil contained no DNA they later changed their tune, and are now claiming that DNA HPV L1 gene in the vaccine is not a contaminant but it is a normal consequence of vaccine production. The remaining DNA fragments are presumed to be safe [13]. The World Health Organization (WHO) had earlier claimed that DNA fragments shorter than 200 base pairs should be presumed safe [14]. It appears that the Merck Corporation, FDA and WHO are closing ranks to claim that the DNA contaminant in vaccines should be presumed safe without any evidence.
The DNA contaminants in Gardasil such as L1 gene fragments and the probable yeast DNA fragments such as the GAL1-GAL10 promoter and the ADH1 terminator flanking the synthetic L1 gene used to produce the vaccine, may pose no threat to the victims of Gardasil vaccination. But it is totally unacceptable to presume that they are safe for human vaccination without experimental evidence or evaluation. Indeed, short DNA fragments can be incorporated into the human genome. Although the yeast used to produce the vaccine does not have the small regulatory RNA employed by most organisms from bacteria to humans, it does contain 247 small open reading frames including 22 short DNA sequences specifying peptides involved in cell growth or damage and growth in the presence of DNA damage and replication arrest. At least one yeast gene product inactivates the cancer suppressor gene p53 and in that way promotes cancer in multicellular organisms [15]. The integration of the L1 and/or yeast genes may enhance the chances of acquiring cancer in numerous tissues of the body. It has been known for many years that ingested DNA may be covalently linked to mammalian DNA in blood cells, liver cells, spleen macrophages and T cells [16], and horizontal gene transfer and recombination via circulating nucleic acids is now well known [17] (Intercommunication via Circulating Nucleic Acids, SiS 42) .
Cervarix contains recombinant C-terminally truncated (shortened) major capsid L1 proteins of HPV types 16 and 18 as active ingredients. The L1 proteins of HPV-16 and HPV-18 are separately produced using a recombinant baculovirus expression system and the insect cell line Hi-5 Rix4446 derived from Trichoplusia. After extracting the L1 proteins and further purification, they are assembled separately as VLPs. The VLPs of each HPV type are formulated with the AS04 adjuvant system composed of aluminium hydroxide and 3-O-desacyl-4.-monophosphoryl lipid A (MPL). The MPL immunostimulant is a detoxified derivative of the lipopolysaccharide of the gram negative bacterium Salmonella minnesota R595 strain. Host cell proteins (HCP), DNA, and infectious recombinant baculovirus DNA are potential impurities removed in the preparation process. Other impurities such as lipids or carbohydrates are present only in negligible trace amounts [18].
Cervarix’s manufacturer maintains that the vaccine is not contaminated with DNA or other products from the baculovirus vector or the insect cells. The baculovirus, Autographa californica nucleopolyhedrovirus (AcMNPV) for which the complete genome sequence has been determined, has a circular, double-stranded, super-coiled DNA genome of approximately 130 kilobases packaged in a rod-shaped nucleocapsid. These nucleocapsids can be extended lengthways and thus the virus genome can effectively accommodate large insertions of foreign DNA. Such insertions of foreign genes into the AcMNPV genome has resulted in production of baculovirus expression vectors; recombinant viruses genetically modified to contain a foreign gene of interest, which can be expressed in insect cells under the control of a baculovirus gene promoter [19]. Baculovirus infects and is viable in human cells. Baculoviruses mediate gene expression in a wide array of vertebrate cells including those of humans [20] and numerous baculovirus genes are expressed in human cells [21, 22]. Baculoviruses contain two genes that prevent apoptosis and in that way facilitate progress of cancer cells [23]. Baculoviruses contain small DNA genes coding for micro RNAs with 8 viral and 64 cellular targets including interference with the host immune defence machinery [24]. There is clear evidence that the baculovirus vector DNA harbours genes detrimental to humans. It is imperative that DNA and RNA along with proteins from baculovirus and insect cells should not contaminate Cervarix vaccine.
DNA contamination of HPV vaccines is a serious problem, and not a normal or acceptable consequence of recombinant vaccine production as claimed by FDA. The false claims of FDA put into serious question not only Gardasil but also Cervarix. A truly independent agency is urgently required to undertake studies on the content of contaminating DNA and of RNA in the two vaccines.
Article first published 12/09/12
Got something to say about this page? Comment
There are 8 comments on this article so far. Add your comment above.
Sandy Lunoe Comment left 12th September 2012 23:11:58
Excellent article. However, I beg to differ on one point:
In the section for HPV Vaccines it is stated "They are prophylactic, that is, they prevent cervical cancer but do not cure existing infections".
It has not yet been shown that the HPV vaccines prevent cervical cervical cancer.
Meryl Dorey Comment left 13th September 2012 06:06:40
I agree - this is an excellent article and it deserves widespread media attention but we know that the mainstream media will ignore this just as it ignores anything else that questions the safety or effectiveness of vaccines.
What I am confused about - and I have always wondered this - is why the KNOWN contamination of all vaccines never mentioned. Why are fragments of DNA from the HPV virus all of a sudden dangerous when contamination with monkey, dog, horse and human viruses in all other vaccines not a matter for concern (the only potential exception is the HepB vaccine but considering the fact that its production is not that different to the production of HPV vaccines, there may also be contamination there)?
We are not allowed to use xenotransplantation for fear of mixing viruses and bacteria from animal species into the human genome - but we have been doing this for over 200 years through the practice of vaccination (originally the pus and blood of cows) without anyone asking the obvious question - could this practice not only be seeding the human race with new and potentially deadly diseases (eg HIV, Ebola, etc), but can it also be changing our genetic makeup - perhaps not for the better?
These are questions that need to be asked and looking at the HPV DNA contamination of Gardasil and Cervarix is a great place to start. I'm just saying it is not the finish line - if we are concerned about contamination, we need to be concerned about ALL contamination.
Meryl Dorey
Australian Vaccination Network, Inc.
Todd Millions Comment left 13th September 2012 19:07:36
This has being a persistent problem since -'variation',was brought back too england from turkey in the 1600's.The weakened small pox pus,produced by keeping it in a bound up walnut shell,between a womens breasts(as was bread dough and beer starter) for 'a moon',was pressed under the skin too cause a mild smallpox infection that children would survive,undisfigured.
Too strong a starter strain,or other contaminates were a risk.Sometimes producing epidemics that this was meant too prevent.Thus cow pox was seen as a great improvement.
Later,my grandparents were very concerned about the mercury based preservitive that the polio vaccines required,all others at the time were preserved with salt,and multigenreationa rat studies had already indicated pup imparment by the mercury based stabilizers.Add too this the contamination by shabby manufacuting standards health/pharmawhore canaduh is now NOT noticing...
These DNA/RNA contaminates,may be of some use in tracking how the moded fragments travel through the body.Which may be of use to track the same on GM crops.Something health and ag athourities are being extemely slow and very able NOT doing.
joe cummins Comment left 14th September 2012 05:05:28
In reply to Sandy Lunoe. Meryl Dorey and Todd Millions: Your comments are valuable and appreciated. Describing HPV vaccines as being prophylactic is used to differentiate them from therapeutic vaccines which are being developed to treat ongoing cervical cancers. It has not yet been proven that prophylactic vaccines prevent cancer. However, it has been found that HPV is found in 99.7% of cervical cancers. It has been shown that the prophylactic vaccines greatly reduce HPV infections of the types for which the vaccines are designed. For that reason it is probably safe to assume that the absence of virus infection will mean that cervical cancers will not be found. However, time alone will tell weather cervical cancers will be reduced by vaccination.
The special hazard of DNA and RNA contamination in vaccines is that fragments of DNA from HPV have been shown to be present in the chromosomes cervical cancer cells. Finding DNA fragments from the virus in the vaccine may pose the threat that the DNA fragments will be introduced into the chromosomes of human cells leading those cells to become cancerous. Some small RNA fragments may also act make human cells cancerous. The HPV L1 gene DNA identified in the contaminated vaccines are not likely able to cause human cells to become cancerous but fuller measurements on all of the DNA fragments in the vaccine is essential because manufacture of the vaccine involves plasmids ( small chromosomes) containing the L1 gene with flanking genes for transcription of the L1 gene from the virus coat used to make up the vaccine along with genes for propagating the plasmid in yeast or insect cells. Some of those genes are known to produce proteins or RNA that promote cancer in human cells (oncogenes).
One aspect of the DNA contamination of vaccines was very disturbing. Initially the manufacturer claimed that the vaccine was free of DNA. When contaminating DNA was independently discovered in vaccines the manufacturer acknowledged that DNA contamination was expected because of the manufacturing process. Both FDA and World Health Organization (WHO) accepted conclusions of the manufacturer without comment or fuller effort to examine the contaminating DNA. The 'regulatory' agencies further presumed that DNA fragments less than 300 bases long were safe for contamination even though they should have been aware that RNA oncogenes copied from DNA are much smaller than 300 bases long! To conclude, we must insist that the DNA contaminants in the HPV vaccines be full sequenced and identified before many more girls and young men are vaccinated. The regulators must not be allowed further cover up.
Sandy Lunoe Comment left 20th September 2012 07:07:26
As someone who is obviously serious about scientific truth, I am sure you will agree it is simply not acceptable to expose a healthy population of young women to the inherent risks of vaccination on the chance that a few cases of cervical cancer may be averted. This is particularly true when you consider the fact that normal cervical screening practices, already proven as a safe and effective means to control this disease, are still required.
Elizabeth Hart Comment left 17th June 2015 15:03:23
The fast-tracked roll-out of HPV vaccination to all the world’s children is a massive international experiment. The current generation of children are the guinea pigs for HPV vaccination, but they don’t know that.
In Australia, the Gardasil HPV vaccine product was originally rejected by the Pharmaceutical Benefits Advisory Committee (PBAC) in 2006. After then Prime Minister John Howard’s interference, this decision was over-turned[1] and Gardasil was fast-tracked onto the National Immunisation Program Schedule.
According to an Archived Fact Sheet – Australian Government Funding of Gardasil, the PBAC agreed to accelerate its processes to support a 2007 roll-out of Gardasil, despite the fact Australia had "the second-lowest incidence of cervical cancer and the lowest mortality rate from cervical cancer in the world."[2]
Subsequently, HPV vaccination has been promoted around the world.
Personally, I am flabbergasted by the way experimental HPV vaccination has been fast-tracked and pushed onto mass populations of children.
Children and their parents are not being properly informed about experimental HPV vaccination.
We have no idea of the long term consequences of HPV vaccination. As far as I am aware, there is no evidence that HPV vaccination has prevented cervical cancer or death from cervical cancer.
If HPV vaccination is as effective as claimed, we do not know the potential for waning efficacy or possibility of type replacement. (For example in an article in New Scientist in September 2011, Charlotte Haug raised some questions about HPV vaccination, including “…what effect will the vaccine have on the other cancer-causing strains of HPV? Nature never leaves a void, so if HPV-16 and HPV-18 are suppressed by an effective vaccine, other strains of the virus will take their place. The question is, will these strains cause cervical cancer?”[3])
Up to now the ‘consent’ process has been a rote exercise, in my opinion. But now with Tony Abbott’s recent edict that vaccination will be compulsory for children of all ages to access family tax benefits[4], children in Australia will be forced to have the Gardasil vaccine product if their parents want/need to access financial benefits.
I suggest this financial inducement for vaccination contravenes the obligation for legally valid consent before vaccination, as detailed in The Australian Immunisation Handbook, 2.1.3[5], i.e.
QUOTE
For consent to be legally valid, the following elements must be present:
1. It must be given by a person with legal capacity, and of sufficient intellectual capacity to understand the implications of being vaccinated.
2. It must be given voluntarily in the absence of undue pressure, coercion or manipulation.
3. It must cover the specific procedure that is to be performed.
4. It can only be given after the potential risks and benefits of the relevant vaccine, risks of not having it and any alternative options have been explained to the individual.
END OF QUOTE
For consent to be legally valid, “it must be given voluntarily in the absence of undue pressure, coercion or manipulation”. Obviously parents and their children are now being pressured/coerced/manipulated into having HPV vaccination with financial inducement, so how can their ‘consent’ be legally valid?
In regards to point 4, I suggest the risks of the HPV virus are being exaggerated by parties promoting HPV vaccination, and parents and their children are not being informed that HPV vaccination is experimental in regards to unknown long-term consequences, potential waning efficacy, or possibility of type replacement. Again, in this instance, as parents and their children are not being properly informed, I do not see how they can give ‘legally valid’ consent to this medical intervention.
I suggest this matter requires urgent legal scrutiny.
References:
[1] Haas, Marion. “Government response to PBAC recommendations”. Health Policy Monitor, March 2007: http://hpm.org/en/Surveys/CHERE-Australia/09/Government_response_to_PBAC_recommendations.html
[2] Archived Fact Sheet - Australian Government Funding of Gardasil: http://archive.is/pm19
[3] We need to talk about HPV vaccination – seriously. New Scientist, 16 September 2011: http://www.newscientist.com/article/dn20928-we-need-to-talk-about-hpv-vaccination--seriously.html?full=true#.VWATevmqqko
[4] No Jab – No Play and No Pay for Child Care. Media Release – Prime Minister of Australia, The Hon Tony Abbott MP. 12 April 2015: https://www.pm.gov.au/media/2015-04-12/no-jab-no-play-and-no-pay-child-care-0
[5] 2.1.3 Valid consent. The Australian Immunisation Handbook 10th Edition 2013 (updated January 2014): http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part2~handbook10-2-1
Elizabeth Hart Comment left 17th June 2015 15:03:04
Further to my previous comment, the UK Daily Mail also asks (2 June 2015): "Just how safe is the cervical cancer jab? More and more families say their daughters suffered devastating side-effects from the HPV vaccine and experts are worried too." (2 June 2015.) http://www.dailymail.co.uk/health/article-3106372/Just-safe-cervical-cancer-jab-families-say-daughters-suffered-devastating-effects-HPV-vaccine-experts-worried-too.html
The Daily Mail article quotes: “British epidemiologist Dr Tom Jefferson, a global authority on vaccine trial evidence, who works for the scientific body, the Cochrane Collaboration. ‘The HPV vaccine’s benefits have been hyped and the harms hardly investigated,’ he says. He is highly critical of the drug company funded clinical trial data that is used to justify the use of mass vaccination. He adds that pharmaceutical companies may hide negative results deep in their trial data and hugely inflate the benefits. ‘The reason for introducing vaccination against HPV was to prevent cancer,’ he says. ‘But there is no clinical evidence to prove it will do that. We have to tread a very careful line, weighing the potential benefits and harms that a vaccine may cause. With HPV, the harms have not been properly studied. ‘It is extremely difficult to publish anything against HPV vaccination. Vaccines have become like a religion. They are not something you question. If you do, you are seen as being an anti-vaccine extremist. The authorities do not want to hear “side-effect”.”
Sarah Comment left 22nd September 2016 23:11:51
What can be done if we have already had the Gardasil vaccine? I feel like a science experiment. I can only assume that I will end up with cervical cancer, the very thing I was trying to avoid. Thanks for nothing, Merck.