Underground Knowledge — A discussion group discussion

Excerpt from Chapter 42 in Vaccine Science Revisited: Are Childhood Immunizations As Safe As Claimed?:

Rotavirus – The runs

“When health is absent, wisdom cannot reveal itself, art cannot manifest, strength cannot fight, wealth becomes useless, and intelligence cannot be applied.” ― Herophilus (Greek physician)


Rotavirus causes severe diarrhea. Unless you don’t have access to hospital care, even the most severe case is normally not a huge concern. This is because the main side effect of severe diarrhea is dehydration, and in hospital it will be treated with IV fluids. In countries which lack medical care, diarrhea is a very serious illness.

A paper from the Cochrane Library in 2012 states that:

“Rotavirus results in more diarrhoea‐related deaths in children less than five years of age than any other single agent in countries with high childhood mortality. It is also a common cause of diarrhoea‐related hospital admissions in countries with low childhood mortality.”

Although there may be disagreement over the need of this vaccine in areas with good healthcare, it may save lives in other areas of the world.

Dr, Leonard Friedland who works for GlaxoSmithKline (GSK) said during a hearing arranged by the FDA in 2010 that:

“[…] rotavirus infection is the leading cause of severe diarrhea in both developed and developing countries. Prior to the development of vaccines against rotavirus, worldwide one child died from rotavirus every minute. To date, vaccination is the only effective preventative strategy. Its widespread use has the potential to prevent about two million deaths over the next decade.”

We can see how scary this disease is for people in developing countries who experience the severity of the rotavirus on a regular basis. So why the controversy towards a vaccine that is designed to save literally millions of lives?


Trials

As we have mentioned before, it seems difficult to figure out how any conclusions can be drawn from vaccine trials. We are aware of the guidelines the researchers have to follow. One of those guidelines being that it’s unethical to give a salt solution as the placebo when there’s an effective vaccine against the germ. Therefore, it’s not surprising that the placebo is never specified as being a saline solution. It most likely isn’t saline. It should never be expected that it is, unless specified.

We looked at both Rotateq and Rotarix study designs. Neither specifies what they used as a placebo. We are surprised this is not a requirement. The RotaTeq vaccine study design states their placebo matched that of the RotaTeq vaccine. We’re not sure what that means, although it sounds like a different brand or version of rotavirus vaccine may have been used. In addition, as with so many if not most vaccine trials, the vaccines were not given alone. They were given in combination with HepB, flu, DTaP, pneumococcal and polio vaccines.

As before, we have difficulty understanding how it’s possible to know which events are related to each vaccine. Because these trials usually include other vaccines as well, we are not certain how the scientists know which vaccine or component to attribute a side effect to.

Is it possible a vaccine is deemed safe because its side-effects are attributed to or labeled under the wrong vaccine?

With these biases and the inherent significant errors in mind, the clinical studies reported 52 deaths:

“There were 25 deaths in the RotaTeq recipients compared to 27 deaths in the placebo recipients. The most common cause of death was sudden infant death syndrome.”

In regards to the Rotarix vaccine, combining observations made in eight clinical trials, the scientists reported a total of 68 deaths after vaccination with the Rotarix vaccine and 50 “deaths following placebo administration.” They also observed that “[t]he most common cause of death following vaccination was pneumonia, [...]”.

Another serious adverse event common enough to receive special mention in package inserts for both RotaTeq and Rotarix is the ailment known as intussusception. This is an obstruction in the infants’ bowels. As we mentioned, this is when the bowels more or less fold in on themselves, much like a telescope. Blood is no longer able to flow properly through the intestines and the rectum starts bleeding.

Severe combined immunodeficiency (SCID) has been associated with the rotavirus vaccine. This is when infants start out with prolonged gastroenteritis and are later diagnosed with SCID. So, in December 2009, Rotateq added SCID as a contraindication to its label.

According to Dr. David Martin, who works for the FDA, in 2010 GSK were in the middle of conducting two controlled observational studies.
Regarding these trials and referring to the Vaccine Safety Data (VSD), Dr. Martin said at that time, that:

“[…] less than 5,000 doses have been administered. Outcomes include intussusception, seizures, meningitis/encephalitis, myocarditis, gram negative sepsis, gastrointestinal bleeding, Kawasaki disease, and hospitalized pneumonia.”

Vaccine manufacturers are permitted to use cell material from bodies of mammals, including humans, monkeys, cows, pigs, dogs and rodents as well as cells from birds and insects in either experimental or currently licensed vaccines. They are even experimenting with human fetal retinal cells, which have a history of causing cancerous cells in animals.
So, have other cells they use for making vaccine.

Scientists can’t actually explain why the Rotarix vaccine works. They don’t
understand how the body’s antibody production against this vaccine works or how it plays a part in protection against the actual disease. All they are sure of is that the vaccine makes its way into the small intestine and triggers an immune response.


Side effects

The Rotarix and RotaTeq vaccines are made slightly different, but the rotavirus for both vaccines was derived from human cells. In addition, the RotaTeq virus was also taken from a bovine source. The rotaviruses were then propagated in Vero cells. As you may recall, Vero cells are African green monkey kidney cells which are grown in fetal bovine serum (FBS).
In 2009, a study was performed on physicians’ vaccination practices. Some 25 out of 416 general practitioners said they would not vaccinate for rotavirus and 16 out of 138 subspecialists would not vaccinate for rotavirus.

Out of 70 physicians, 63 had their own children opt out of at least one of the vaccines. The reason they gave were safety and too many vaccines given at once.

The reasons given (for opting out) specifically for the rotavirus include:

“In developed countries Rotavirus is for the most part treatable and I’ve seen some side effects.

“Severity of illness itself is usually not severe enough to warrant vaccination (rotavirus).”

Apart from all the ingredients purposely added to vaccines in the manufacturing stage, the rotavirus vaccines are better known for other contaminants that made their way into the vaccine.

The most infamous rotavirus vaccine contaminants have been identified as porcine circoviruses 1 and 2 (PCV1 and PCV2). We look at these in the next chapter.


References in Chapter 42: Rotavirus – The runs
Soares-Weiser, K., Maclehose, H., Bergman, H., Ben-Aharon, I., Nagpal, S., Goldberg, E., … Cunliffe, N. (2012). Vaccines for preventing rotavirus diarrhoea: vaccines in use. Cochrane Database of Systematic Reviews, 11, CD008521
Food and Drug Administration. and Center for Biologics Evaluation and Research. (2010, May 7). FDA Vaccine and Related Biological Product Advisory Committee Meeting. [Transcript]. Retrieved from https://wayback.archive-it.org/7993/2...
NIH U.S. National Library of Medicine. (2015, October 5). Rotavirus Efficacy and Safety Trial (REST)(V260-006). Retrieve from https://clinicaltrials.gov/ct2/show/r...
https://clinicaltrials.gov/ct2/show/r...
NIH U.S. National Library of Medicine. (2018, June 8). Efficacy, Safety, Reactogenicity & Immunogenicity of the Rotarix Vaccine in Japanese Infants. Retrieved from https://clinicaltrials.gov/ct2/show/N...
Food and Drug Administration. (2017, February). RotaTeq. Retrieved from https://www.fda.gov/downloads/biologi...
Food and Drug Administration. (n.d.). Rotarix. Retrieved from https://www.fda.gov/downloads/biologi...
Food and Drug Administration. and Center for Biologics Evaluation and Research. (2010, May 7). FDA Vaccine and Related Biological Product Advisory Committee Meeting. [Transcript. p. 15]. Retrieved from https://wayback.archive-it.org/7993/2...
Food and Drug Administration. (n.d.). Rotarix. Retrieved from https://www.fda.gov/downloads/biologi...
Martin, M. and Badalyan, V. (2012). Vaccination practices among physicians and their children. Open Journal of Pediatrics, 2, 228-235.

Excerpt from Chapter 43 in Vaccine Science Revisited: Are Childhood Immunizations As Safe As Claimed?:

Rotavirus – and the porcine invaders

“We can’t predict what a virus we’ve never seen will do.” Marc Lipsitch (Professor of Epidemiology)


Many uninvited guests, or as scientists would call them, adventitious agents, find their way into the vaccine manufacturing process. These agents fall into many categories, including bacteria, mycoplasma, parasites and viruses. The PCV1 and PCV2 viruses were uninvited agents that were discovered in the rotavirus vaccines.

In the manufacturing process for Rotarix and RotaTeq, DNA from PCV1 was detected. In the RotaTeq, PCV1 and PCV2 were detected. This was even acknowledged in their package inserts.

Multiple studies can be found online that indicate that PCV1 is harmless in pigs and PCV2 is pathogenic in pigs, but there is no evidence of either causing harm to humans. Therefore, the manufacturers have not seen a reason to remove these particles from vaccines.

That said, it’s interesting to note the FDA expresses safety concerns yet allows unintended viruses, which they can’t guarantee won’t mutate, remain in the vaccines. As a matter of fact, the National Vaccine Information Center (NVIC), together with Dr. Joseph Mercola fought to take RotaTeq (Merck) vaccine off the market. They said the vaccine was “contaminated with parts of a lethal virus that infects pigs – porcine circovirus 2 (PCV2)” and wanted Merck to “publicly pledge to clean-up the vaccine.”

On May 7th, 2010, GSK, producer of the Rotarix vaccine, admitted their vaccine was infected with the non-lethal virus PCV1. They also “publicly pledged to re-formulate the
rotavirus vaccine”. GSK ended up removing the PCV1 from their vaccines. Merck did not follow suit.

There seems to be more concern over the RotaTeq (Merck) vaccine as it’s the one that contains the PCV2 virus.

The NVIC website continues by explaining how in the end, the FDA decided to revoke their “suspension of Rotarix vaccine recommendation and” deem both Rotarix and RotaTeq vaccines safe. They did this knowing that both vaccines “remain contaminated and safety data on PCV2 contamination of RotaTeq was not evaluated by the FDA advisory committee.”

Circoviruses such as PCV are the smallest viruses we know of. The filters used for viruses in vaccine manufacturing are not known to protect against them as the PCV particles are too small. Regular inactivation methods do not work on PCVs.

There are multiple biological products being used in the manufacturing of vaccines. Many of these are a source of viral contaminants. We have, for instance, blood and trypsin that are taken from a common source and used in multiple vaccines. This has prompted investigations to see whether PCV1 is present in the stocks of these materials.

The polio vaccine (IPV) manufactured by GSK uses the same master Vero cell bank as the Rotarix vaccine does. They tested the beginning phases of the manufacturing process of IPV and the final product. PCV1 was found in the beginning phases, but by the time they had finished the process, the vaccine tested negative for the PCV1 virus.

After much investigation, both PCV1 and PCV2 were said to be safe for humans. Not everyone agrees with these findings. It was a big enough concern that in 2010 the advisory committee held a hearing to discuss the matter.

In this 2010 hearing, Dr. Barbara Howe, Vice President and Director of North American Vaccine Development for GSK at the time stated:

“It is known that PCV1 causes widespread infection in pigs. For example, about 60-95 percent of pigs tested in Germany and 26 to 55 percent of pigs tested in Canada are positive for PCV1 antibodies.”

Dr. Howe shares observations found in other studies and continues:

“Therefore, the available data indicates that the PCV1 is not pathogenic. In fact, the non-pathogenic virus, the PCV1 is used as a vaccine vector in the first USDA fully-licensed kill vaccine against PCV2.”

The vaccine manufacturers were questioned about the circovirus contaminations in their vaccines and a couple of specific research studies were used as examples. However, there is no reference to them in the transcript. We only know them by the names of their authors, the Hattermann study and the Li study.

When looking for the presence of PCV, the Li study only tested the antibodies in the blood. In the Hattermann study, they used samples of blood, urine and lymph nodes to look for DNA. Neither study used stool samples to look for viral DNA.

Dr. Andrew Cheung who at the time, worked for the USDA Agriculture Research Service in Ames, Iowa, referred to a study performed in Canada. In this study they observed the two viruses, PCV1 and PCV2, recombine.

As far as we know, there have not been any studies done on how immunosuppressed pigs or immunosuppressed humans would react if infected with PCV1.

The porcine circovirus expert, Dr. X.J Meng , a professor of Molecular Virology at the

College of Veterinary Medicine, Virginia Tech., has been studying this virus since 1999. Dr. Meng states that an infectious clone of PCV1 exists in pigs.

It seems nobody is sufficiently concerned to look at human cells yet. Easier to stick to animal studies perhaps.

Dr. Emmanuel Hanon, Vice President of Early Research and Development for GSK, states that GSK speculates the PCV1 comes from the trypsin they used when producing their master cell bank (MCB). In order to eliminate PCV1 from the vaccines, they would have to create a new cell bank and begin a long process spanning several years. This would necessitate conducting new clinical trials for the vaccines.

A Master Cell Bank (MCB) takes the cell lines produced in a lab and tests them for authenticity, viability and contamination. Then they culture them in the ideal setting for optimal growth and then store them in most appropriate way. The MCB keeps very detailed records of all information pertaining to the cells they store, encouraging manufacturing companies to return to acquire cells for their cultures.

Dr. Hanon explains how they had found a PCV1 messenger RNA (mRNA), which is a sign that the viral particle can cause disease. The mRNA is a very important part of the coding process. It takes the DNA information out of the cell nucleus and carries it into the part of the cell that makes proteins. So finding a viral particle containing mRNA is finding a viral particle carrying genetic information.

The vaccine manufacturer GSK doesn’t seem concerned about these findings even though the infected PCV1 gene multiplies in human cells. The reason given is because that wouldn’t trigger a “productive infection”.

Dr. Gary Dubin, Vice President of Global Clinical Development at GSK, states:

“[…] there is evidence of a detection of rotavirus antigen in stools in a sizeable proportion of infants for a limited period of time. It tends to be detected later, and it tends to persist for a longer period of time, which reflects, we think, the nature of the fact that the virus in the vaccine does cause limited replication in the gut, and that is part of the mechanism of action.”

The concerns and study trials relating to the PCV1 in Rotarix have led to an amendment in the post-marketing part of the package insert.

The following has been added:

“[…] intussusception including death and temporal association, Kawasaki disease and rotavirus gastroenteritis in patients with severe combined immunodeficiency syndrome.”

One of the most intriguing statements to come from this hearing was made by a guest speaker, Dr. Gordon Allan from Queen’s University of Belfast. He was speaking as an expert in porcine circoviruses. Dr. Allan explained that in order to trigger a good PCV2 infection in pigs, you first infect them with the virus and then you stimulate their immune system. The immune system is stimulated by either infecting them again or by giving them a vaccine.

Dr. Allan continues:

“I don't know what the vaccination schedule for children is, but if you are giving them PCV1 and then giving them another vaccine, you are immuno stimulating them. I'm not saying it is dangerous. I'm just pointing out that for PCV2 in pigs, you will not get good disease unless you immunostimulate them, not immunosuppress them, immunostimulate them.”

Dr. Harry Greenberg with Stanford University made a good point when he suggested that it would be nice to see studies done on the effect the vaccine has on severely immunosuppressed children. He pointed out although they should not receive the vaccine, they still do, as they are not always diagnosed as immunosuppressed until after vaccination.

Another worthy suggestion was made by Dr. Pablo Sanchez with University of Texas, Southwestern Medical Center, in Dallas. He wanted to know if it was possible to look for PCV in various tissues in infants who died after receiving the vaccine. For instance, the infants who die from SIDS are already being autopsied, so a large-scale study could be conducted on testing the various tissues in these infants.

There’s obviously much awareness of adventitious agents, or uninvited guests, in the vaccines. Studies are being funded to look into their effects, but we can’t help wonder why every aspect is not being covered given the opportunity to do so is there? It appears researchers are still using small sample sizes, only looking at healthy infants and limiting the sources they derive their samples from.

We also wonder if they considered the fact that it could take a while for a virus to replicate. Not all viruses replicate and infect at the same rate. So, when researchers say a virus replicates and doesn’t cause infection in human cells, did they also look at the rate it was replicating at? What if it takes X amount of viruses before disease results, but the study did not last long enough to determine whether this were to occur? Or, while replicating in human cells, at what rate did the virus mutate? Did the mutations replicate faster or were they more invasive?

We feel some of these questions could be answered by following through with the excellent suggestions made by doctors Sanchez and Greenberg regarding how to gain a better understanding of the true effects the PCV1 & 2 has on infants.

References for Chapter 43: Rotavirus – and the porcine invaders:

Mercola. (2019, January 19). Mercola. Take Control of Your Health. Retrieved from https://www.mercola.com/
National Vaccine Information Center. (2010, May 20). Vaccine Safety Critics Call For RotaTeq Vaccine Recall & Clean-Up. Retrieved from https://www.nvic.org/NVIC-Vaccine-New...
Ibid.
Ibid.
Ibid.
FDA Vaccine and Related Biological Product Advisory Committee Meeting. (2010 May 7). (Testimony of Dr. Barbara Howe). [Transcript. p. 33]. Retrieved from https://wayback.archive-it.org/7993/2...
FDA Vaccine and Related Biological Product Advisory Committee Meeting. [Transcript. pp. 33-34]. Retrieved from https://wayback.archive-it.org/7993/2...
Federal Pay. (n.d.). Federal Employee Profile – Andrew K. Cheung. Retrieved from https://www.federalpay.org/employees/...
FDA Vaccine and Related Biological Product Advisory Committee Meeting. (2010 May 7). (Testimony of Andrew K. Cheung). [Transcript. p. 39]. Retrieved from https://wayback.archive-it.org/7993/2...
Virginia-Maryland College of Veterinary Medicine. (n.d.). Biomedical Sciences & Pathology Faculty. Retrieved from http://www.vetmed.vt.edu/people/bios/...
FDA Vaccine and Related Biological Product Advisory Committee Meeting. [Transcript. p. 39]. Retrieved from https://wayback.archive-it.org/7993/2...
My Bio. (n.d.). Bio International Convention, Personal Event Planner. Retrieved from https://mybio.org/profile/member/1122068
FDA Vaccine and Related Biological Product Advisory Committee Meeting. (2010 May 7). (Testimony of Dr. Emmanuel Hanon). [Transcript. p. 42]. Retrieved from https://wayback.archive-it.org/7993/2...
FDA Vaccine and Related Biological Product Advisory Committee Meeting. [Transcript. p. 44]. Retrieved from https://wayback.archive-it.org/7993/2...
NIH National Human Genome Research Institute. (n.d.). Messenger RNA (mRNA). Retrieved from https://www.genome.gov/glossary/index...
FDA Vaccine and Related Biological Product Advisory Committee Meeting. (2010 May 7). (Testimony of Dr. Gary Dubin). [Transcript. p. 68]. Retrieved from https://wayback.archive-it.org/7993/2...
FDA Vaccine and Related Biological Product Advisory Committee Meeting. [Transcript. pp. 78-79]. Retrieved from https://wayback.archive-it.org/7993/2...
Queen’s University Belfast. (n.d.). Professor Gordon Allan. Retrieved from https://pure.qub.ac.uk/portal/en/pers...
FDA Vaccine and Related Biological Product Advisory Committee Meeting. (2010 May 7). (Testimony of Dr. Gordon Allan). [Transcript. p. 112]. Retrieved from https://wayback.archive-it.org/7993/2...
Stanford University. (n.d.). Harry B Greenberg. Retrieved from https://profiles.stanford.edu/harry-g...
Nationwide Children’s. (n.d.). Pablo J. Sanchez. MD. Retrieved from https://www.nationwidechildrens.org/f...