Cervarix: An M-cell-specific targeted mucosal vaccine

Cell Specific Vaccine

By Suk Ho Lim, 25 January 2015

I first became involved with this disease when I received a letter from the parents of a young woman who requested chiropractic therapy for their daughter. Since that time I have treated about 30 patients suffering from this mysterious disease. The symptoms resemble those of many of the autoimmune disorders. The people afflicted with this disease have difficulty leading normal lives. Their trouble began after they took the advice of their doctors and received a 3-dose vaccination series that had been developed by a pharmaceutical company to prevent cervical cancer. Many of these young people took the vaccination series at about age 12—just at the time they entered junior high school.

I would like to begin this series of articles with a description of the drug Cervarix, a product of GlaxoSmithKline KK (GSK), and I would like to explain some of the important things I have learned about it. Many people have offered opinions and points of view about this vaccine on the internet and in a variety of publications. Because of the wealth of information about Cervarix that is easily accessible on the web, I will not give a full description here. I strongly recommend that you conduct your own search of available literature. The information presented here is the result of my personal investigation.

According to the published recommendations of GSK, Cervarix should be administered to females between the ages of 11 and 20 years. Although intramuscular injections were banned in Japan for some 30 years, this ban has been lifted and no longer blocks the intramuscular injection of the Cervarix vaccination series.

The characteristics of Cervarix are:

1) The active components of the vaccine are:

• Human Papillomavirus type 16 L1 protein 20 micrograms
• Human Papillomavirus type 18 L1 protein 20 micrograms
• AS04 adjuvant, containing: 3-O-desacyl-4′-monophosphoryl lipid A (MPL) 50 micrograms adsorbed on aluminium hydroxide, hydrated (Al (OH)₃) 0.5 milligrams Al 3+ in total.

2) it is cultivated within the body of the moth Trichoplusia ni;

3) it is a genetically modified (gene recombination) baculovirus of insect origin;

4) it is a gene recombination of salmonella endotoxin;

5) it functions as a monoclonal antibody;

6) it contains substances that are not included in the specifications; the

7) the presence of antigens.

In response to initial fears about the potential danger of the aluminium content of Cervarix, a number of articles were published in the media that claimed that the amount of aluminium was too small to cause any harm and that in any case the aluminium is discharged within a month of vaccination. The aluminium-bearing adjuvant is beneficial because it increases immune-reactivity and because it increases the stability of the active agent. These articles stated that, although people with organic or genetic disease of the circulatory system or kidney should not take Cervarix, healthy individuals need not worry about taking it. It does, however, cause swelling, redness, and pain at the injection site. Therefore it was recommended that the injection site be either the deltoid muscle or the muscles overlying the femur. In addition, Cervarix reacts with macrophages and cytokines. When the chemosynthetic adjuvant is taken into the body it becomes trapped at sites between cells, making it difficult to excrete.

Trichoplusia ni is a moth with a grotesque and hair-raising name, but the biochemistry of this moth makes it possible and cost-effective to mass produce the stable, non-infectious virus-like particles (VLPs) that are incorporated into Cervarix. I will talk about this subject in the next article.

Although researchers have been unable to harvest Baculoviridae (baculovirus) from the silkworm, they have found this virus is prevalent in arthropod insects and that it effectively degrades many proteins. It does not infect vertebrates, including humans. However, researchers have discovered how to stabilize VLPs in one of the components of baculovirus. The technique for this was discovered in the 1970s, although it wasn’t until the 1990s that significant progress toward its practical use was achieved by lowering the cost and increasing the reliability of the technique.

General antibodies (polyclonal antibodies) are manufactured against the antigens associated with the animal serum contained in the inoculated material, and they become a mixture of a variety of antibody molecular species. However, the immunoglobulin molecular species itself is in unity with the monoclonal antibody.

The active ingredient of Cervarix is a protein sub-unit and, unlike the so-called chemical agents, it cannot be administered orally. It must be delivered via an intramuscular injection (3 injections are given over a six month period). Two additional drawbacks are that it is expensive, due to the high cost of manufacturing and it cannot cross the cell membrane to each the interior of cells. On the other hand, when this protein sub-unit binds to one of the target molecules, the immune system is stimulated to attack and destroy a high percentage of those targeted molecules. In addition, because the human body contains immunoglobulins, it is easier to predict the side effects of Cervarix. [The preceding was paraphrased from Wikipedia.]

To quickly summarize the minuses and pluses, Cervarix is expensive and is not able to cross the cellular membrane, but it has strong self-proliferating power. Like other vaccines for influenza, it is eliminated from the body in between 2 weeks and one month. It creates intravascular antibodies.

GSK, the maker of Cervarix, published research results in January of 2015 showing that antibody titers remain high for 10 years after vaccination. Serum titers were 10 to 100 times higher than those of natural infections of Human Papilloma Virus Types 16 and 18. Clinical tests showed that in some cases the antibody titer levels produced by Cervarix vaccination was 5000 times higher than that of a natural HPV infection.

The genetically modified salmonella endotoxin Type 4 works as a “GPS” system that locates the M cells in the Peyer’s patch in the intestinal mucosa. There is much yet to learn about the salmonella bacterium, but one thing we do know is that it specifically invades intestinal M cells. In particular, the areas that take in bacteria and virus become targets, and thus the Cervarix VLPs that are contoured similarly to HPV and penetrate to the parietal cell fundal mucous basement membrane of the intestinal tract which also become targets. The dissolved VLPs are absorbed into the parietal cells. The immune system finds them there, reacts to them, and produces antibodies. Without that stimulation of the immune system, there will not be the long continuous production of the needed monoclonal antibodies.

From Wikipedia we learn that a variety of cells, including T-cells, B-cells, fibroblasts, monocytes, endothelial cells, and mesangial cells, all secrete IL-6 under appropriate conditions. When lipopolysaccharide (LPS) binds to the Toll-like receptors on the surface of macrophages, those macrophages secrete a variety of cytokines, starting with IL-6. The Toll-like receptors present the antigens, evoking a strong response from the immune system. The proteins of the Toll-like receptors, therefore, act as a pattern-recognition system that takes its place in the overall functioning of the innate immune system. It seems that the antigen-presentation machinery malfunctions in some people who are vaccinated with Cervarix, causing adverse reactions or side effects that interfere with the natural immunity of those individuals.

Incidentally, the antibody titers in individuals inoculated with Cervarix vary widely. Thus, even though the vaccine has been approved for use and is being prescribed by physicians, the pharmaceutical company and the researchers who developed the vaccine are continuing with research to determine the most effective protocol of dosage, interval, and total number of injections needed in the vaccination series. While that research continues, physicians are advised to use their own discretion and carefully select the best protocol.

Please think about the role of antibodies and the concept of “self-proliferation,” meaning that the production of antibodies does not diminish over time as it should in a normally functioning immune system. This was a “blind spot,” an unanticipated condition that affected some people who were vaccinated with Cervarix. As a result, this vaccine may affect some people beyond the expectation of the developer.

Cervarix and Gardasil both contain Gentamicin, a second-generation aminoglycoside derivative. Again from Wikipedia we learn that Gentamicin is a bactericidal antibiotic that works by binding the 30S subunit of the bacterial ribosome, interrupting protein synthesis. Like all aminoglycosides, when gentamicin is given orally it is not systemically active. This is because after being absorbed in the small intestine it reaches the liver via the portal vein and is then inactivated. For this reason it is administered intravenously, intramuscularly or topically to treat infections.

As you know, antibiotics are pharmaceuticals that kill bacteria or suppress their activity. However, they act not only on the bacterial species they are targeted toward, but also against the indigenous intestinal bacteria in the body. By the way, even though the Japanese government has established pricing for antibiotic medicines, it has not established prices for this vaccine. Also by the way, this vaccine contains antibiotics to stabilize the materials it contains.

Do 10-year-old girls have the same physique, predisposition to disease, weight, developmental status, and internal biochemical functioning as 20-year-old young women? Also consider that this vaccination is administered intramuscularly, not orally. However, it reaches the intestine, specifically the small intestine, where it is absorbed. If second-generation bacteria are allowed to persist, resistant strains will manifest themselves, compromising the ability to clear the infections.

It seems to me that the side effects of those who have received a vaccination series to prevent cervical cancer can be understood as disorders of oral-immunization tolerance and as immunodeficiency followed by infectious disease as a consequence of the malfunctioning of the natural immune system.

I estimate it takes less than 1 hour for intramuscularly administered vaccine medicine to reach the intestinal tract. As soon as it reaches the small intestine, or is even on its way there, the antibiotic will attack the indigenous intestinal bacterial flora and will almost completely destroy it, as if it were acting as the advance troops of an invading army. Components such as aluminium and monophosphoryl lipid A, which is the chemical synthesis surface active agent, will naturally penetrate into the interior of the intestinal basement mucous membrane. This dissolved medicine stimulates the production of monoclonal antibodies, which “self-proliferate” and penetrate into the intestinal wall and travels intravascularly through the Peyer’s Patch of the inner wall of the intestinal tract. It activates Toll-like receptors and dendritic cells and produces lymphocytes th1 and th2. Th-1 triggers an extremely elevated immune response.

This is the process that transfers the natural immunity from a mother to the child she gives birth to, so to speak. It is a very important consideration and has great meaning for the treatment we are discussing here. This is not a story with a happy ending, as if you are able to present an antigen to stimulate a continuing antigen-antibody reaction to control an infection (HPV) that is known to cause cervical cancer.

Because one of the purposes of this vaccine is to provide continuous control, effective antibody reaction must continue 24 hours a day, 365 days a year. Research studies have shown that the intestinal tract controls 80% of the human immune system. It may not be an exaggeration to say that a group of researchers have artificially modified the human immune system. A study by a third-party organization showed, based on the attenuation of the vaccine titer, that robust antibody targeting the HPV vaccine will remain in the body for 20 years. Does this mean there is no help for the girls and young women who are suffering severe side effects? The answer is a resounding “NO.” I would like to talk about this later in my series of articles.

The Japanese Ministry of Health, Labour, and Welfare has reported that there are 2600 victims of this vaccine. However, if you include unreported cases, the number is more than 10,000. The pharmaceutical company has published statistics showing that the incidence of side effects is about 10% one month after vaccination. Because 3,700,000 people have been vaccinated with Cervarix in Japan, it follows that about 370,000 people have had side effects. These side effects may continue for 20 years. It is fair to say that this is a kind of human research.

I wrote the present article as a set of general remarks. However, because this cervical cancer vaccine is becoming well established as a world-wide next-generation vaccine, it is imperative that we carefully characterize and understand the side effects of this vaccine and the mechanisms that underlie them. In future articles, I would like to present more details about those side effects and mechanisms of action.

Cervical cancer vaccines tap into the novel concept of targeting the intestinal tract M cell mucosa. Based on the close match between the chronological order of research development and its entry into the pharmaceutical market, it seems that the original idea for Cervarix must have arisen, and the initial research done, at the University of Tokyo and Institute of Medical Science at the University of Tokyo.

Email Mr. Lim at schirokobe@yahoo.co.jp