Bovine Serum and Serum Contaminants

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Bovine extracts are cow-derived products used in vaccine manufacture. Cow products used include Amino acids Glycerol, Detergents, Gelatin, Enzymes, Blood. 'Cow ta'llow derivatives used in vaccine manufacture include glycerol. Gelatin and some amino acids come from cow bones. Cow skeletal muscle is used to prepare certain complex vaccine media. Many difficult to grow microorganisms required the addition of serum from blood to the growth media.

Vaccine Excipient & Media Summary, Part 2  Included in U.S. Vaccines, by Vaccine

Spongiform Encephalopathy and Immunizations What is Bovine Spongiform Encephalopathy (BSE)? Which bovine derived materials are used in vaccine manufacture? [BSE (bovine spongiform encephalopathy) is a progressive neurological disorder of cattle that results from infection by an unusual transmissible agent called a prion. The nature of the transmissible agent is not well understood. It is commonly known as Mad Cow Disease.] 

Transmissible spongiform encephalopathies (TSE) “There is increasing concern about the troubling possibility that blood or blood products, vaccines and other pharmaceutical products could spread the agent of variant CJD (vCJD) worldwide, especially in countries where BSE has not yet been reported. Bovine derived materials involved in the production of vaccines and other pharmaceutical products could represent a way of potential transmission of the disease.” ['''''The FDA is fully aware that bovine cell substrates can become contaminated with adventitious viruses that are potentially deadly. In a 2004 FDA memo, the FDA states that, “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 astudy published in 2004, researchers found that any cell line could potentially support the propagation of TSE agents.]

WHO Guidelines on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies (pdf) “Production systems also affect the final TSE risk assessment for vaccines.  Many vaccines are prepared from organisms that cannot be treated with harsh methods of extraction or purification without reducing or destroying their antigenicity.  Additional difficulties are inherent in the cell bank and seed lot systems employed in vaccines production.  Concerns with respect to TSE may arise from the animals used for in vivo production or as a source of cells for production in vitro, from components of medium used in production, or from the cell banks or bacterial or viral seeds used to initiate production.” [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 (BSE), commonly known as “mad cow disease.”

June 2017 – Sporadic Creutzfeldt-Jakob Disease in 2 Plasma Product Recipients, United Kingdom (full text) “This report describes 2 cases of sCJD in patients with a history of treatment with UK-sourced plasma products, 1 with a history of hemophilia B and 1 with von Willebrand’s disease. To our knowledge, no previous case of sCJD in a person with a history of extended exposure to plasma products has been reported. It is clearly of concern that there have been 2 such cases in a relatively short period in the UK, where many plasma product recipients have been informed that they are at increased risk for vCJD. However, a causal link between the treatment with plasma products and the onset of sCJD has not been established, and the occurrence of these cases may simply reflect a chance event in the context of systematic surveillance of CJD in large populations.” Comment: There is Fractionated Plasma Products in vaccines – Many FDA regulated products contain bovine products, including food, animal feed, drugs, vaccines, tissues, dietary supplements, cosmetics, medical devices, and there also are theoretical concerns about transmitting CJD and vCJD through the human blood supply from a donor infected with CJD or vCJD. At this time there is no documented transmission of CJD or vCJD through blood/blood products. FDA has a long-standing commitment to consumer protection involving BSE and vCJD.

March 13, 2017 – Sensitization to bovine serum albumin as a possible cause of allergic reactions to vaccines “11/20, 5/20, 2/20, 2/20, 1/20 and 1/20 patients reported allergic reactions to measles containing, JE, rabies primary chick embryo, pentavalent, diphtheria and tetanus, and adult diphtheria and tetanus vaccines, respectively. Only one patient with allergy to vaccines had gelatin specific IgE, whereas IgE to BSA was seen in 73.3%, 90%, 66.6% and 0 of vaccine, beef or CM allergic and non-atopic controls, respectively.”

December 12, 2016 – Adventitious agents and live viral vectored vaccines: Considerations for archiving samples of biological materials for retrospective analysis (abstract)   from full text: “Adventitious agents are defined by the World Health Organization (WHO) as microorganisms that may have been unintentionally introduced into the manufacturing process of a biological medicinal product: these include bacteria, fungi, mycoplasma/spiroplasma, mycobacteria, rickettsia, 'protozoa, parasites, transmissible 'spongiform encephalopathy' (TSE) agents and viruses.”…”The detection of bacteriophage was detected in measles and polio vaccines, reverse transcriptase in measles and mumps vaccines, and the emergence of bovine spongiform encephalopathy (BSE) commonly known as “mad cow disease” in the 1980s, and ultimately the human version variant Creutzfeldt–Jakob disease (vCJD) in the 1990s, led to considerable regulatory deliberations, and also guidance on the use of bovine (and other) materials that could transmit transmissible spongiform encephalopathies (TSE’s).”

January 2016 – Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Products (pdf) “In addition to its indications for direct infusion into patients, albumin may be used in the manufacture of other biological products. For example, it is used in the culture media of certain licensed vaccines or as a stabilizer in certain recombinant clotting factor products. Licensed albumin and albumin contained in other licensed products have never been known to transmit viruses, CJD or vCJD, and laboratory experimental evidence suggests albumin is less likely to contain CJD-like agents when compared with other fractionated products.”…"TSEAC agreed unanimously that labeling for the potential risk of vCJD is warranted for plasma derivatives, including albumin and products containing albumin. The revised recommendations for labeling plasma-derived products, including albumin and products containing plasma-derived albumin in this guidance are based upon current knowledge and the advice from TSEAC. We are not recommending changes to the elements of the warning label for CJD. The transmission of CJD is currently described as a theoretical risk, given that there is no evidence that CJD is transmitted by blood.

Comment: Albumin is used in some licensed vaccines, if vCJD (variant mad cow disease) was contracted from a vaccine would we be told about it? Would we see it in print anywhere? The Transmissible Spongiform Encephalopathies Advisory Committee agreed there is a risk for vCJD using albumin. The recommendations are revised yet they are saying they are not recommending changes. Sounds like the double talk we always hear. 

August 2013 – Bovine Serum Albumin: a double allergy risk (pdf) “BSA-hypersensitivity with urticaria angioedema caused by meat ingestion has been suggested as a possible consequence of a subclinical sensitivity to dog and cat epithelium. Immunoblotting studies on various species of animals have demonstrated that albumins play a role as a pan-allergen in mammals and, being major allergens, they are responsible for sensitization to epithelia that developed ”

November 14, 2012 – Source bovine materials from BSE-free Australia or NZ: CEO’s plea to regulators – Regulators must enforce guidance on sourcing animal-based materials to brand risk assessments legitimate, according to Rocky Mountain Biologicals. “While current '''''guidelines'''''  encourage antibody and vaccine makers to source biomaterials from countries where cases of Bovine spongiform encephalopathy (BSE)  are rare, there is no legal requirement that they comply with this advice.”

June 26, 2012 – Prion propagation, toxicity and degradation “In the past few years, however, a bewildering variety of diseases have been found to share features with prion infections, including cell-to-cell transmission. Here we review these developments and summarize those open questions that we currently deem most interesting in prion biology: how do prions damage their hosts, and how do hosts attempt to neutralize invading prions?

June 11, 2012 – Draft Guidance for Industry: Amendment to “Guidance for Industry: Revised Preventive Measures To Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Products,” Availability (pdf) “Similarly, we are recommending revisions to the labeling for plasma-derived albumin and products containing plasma-derived albumin. In addition to its indications for direct infusion into patients, albumin may be used in the manufacture of other biological products. For example, it is used in the culture media of certain licensed vaccines or as a stabilizer in certain recombinant clotting factor products. Licensed albumin and albumin contained in other licensed products have never been known to transmit viruses, CJD or vCJD, and laboratory experimental evidence suggests albumin is less likely to contain CJD-like agents when compared with other fractionated products (Refs. 8-10).”

June 11, 2012 – How to Minimize the Attack Rate during Multiple Influenza Outbreaks in a Heterogeneous Population (full text) “While vaccines have strongly reduced the morbidity and mortality burden for many infectious diseases that transmit from person to person, outbreaks of varying size and severity are still common, both in developed and developing countries. For these diseases, control measures such as drug therapy and prophylaxis, and social distancing (e.g. quarantine, school or airport closures) are useful strategies.”…”In summary, our study showed that even for relatively low inter-group transmission, at levels that were likely to occur for pathogens such as influenza, the population became synchronized enough to essentially consider them one homogenous population for control purposes. We found that it was best to choose an easily observable sub-population (e.g. schoolchildren) and measure their infection status in real time. Once the right number of infections had accrued (which was determined by the efficacy of the intervention and the length it could be applied), control measures should be started. The proper timing ensured that the control was optimal in the sense that it minimized the attack rate and the level of susceptible people dropped to the level at which herd immunity was reached, but not below.

May 16, 2012 – Iatrogenic Creutzfeldt-Jakob Disease, Final Assessment CME “To reduce infectivity, blood, blood products, and other fluids can be subjected to nanofiltration and prion-affinity ligands which should also be applicable to other biological products, for example, vaccine and stem cell cultures, should they be susceptible to infection. Fragile instruments such as endoscopes and electrodes remain a challenge, but new and gentler methods— alkaline cleaning solutions, phenolics, and gaseous hydrogen peroxide—have proven harmless to instruments and give a high, if not always complete, degree of prion inactivation.”

March 21, 2012 – Cow’s milk and ovalbumin-specific IgG and IgA in children with eczema: low β-lactoglobulin-specific IgG4 levels are associated with cow’s milk allergy “Positive egg SPT was associated with elevated levels of specific IgG to ovalbumin, β-lactoglobulin, and α-casein as well as IgA to α-casein (p < 0.04). Our study thus shows that low β-lactoglobulin-specific serum IgG4 levels may differentiate eczematous infants with CMA from infants who have eczema with only suspected association with CM.”

November 30, 2011 – Candidate Cell Substrates, Vaccine Production, and Transmissible Spongiform Encephalopathies(full text) “To that end we initiated titration experiments of the BSE agent and found at the time of this writing, squirrel monkeys develop TSE when inoculated with BSE brain suspensions at high concentration 10–1 and 10–2 dilutions (work in progress). Given the long incubation time (years) needed to elicit disease in this primate model, we will continue the observation of monkeys inoculated with cell cultures exposed to the BSE agent in an attempt to determine whether low infectivity could potentially be detected in this model….Recent studies showed that passage of TSE agents through different animal species altered key characteristics of the agent, sometimes producing variants with increased virulence or broader host range, as happened when BSE agent was passaged through sheep. Thus, further experiments are needed to evaluate the potential susceptibility of various cultured cell lines to infection with new emerging TSE strains. [Comment: If there is even a slight risk of passing Mad Cow Disease (TBE/BSE) to humans through vaccines, why would **anyone** take the risk?]

August 2011 – Four Independent Molecular Prion Protein Parameters for Discriminating New Cases of C, L, and H Bovine Spongiform Encephalopathy in Cattle “In anticipation of the emergence of more variants of bovine spongiform encephalopathy (BSE), a semi-quantitative display of the following four independent molecular diagnostic prion parameters was designed: N terminus, proteinase K (PK) resistance, glycoprofile, and mixed population. One H BSE case, three L BSE cases, six C BSE cases, and one unusual classical BSE (C BSE) case are reported.”

June 29, 2011 – Methods to select suitable fetal bovine serum for use in quality control assays for the detection of adventitious viruses from biological products. “Production of biological products, especially vaccines, usually requires materials derived from animals, and there are always risks that animal pathogens…could contaminate the final products. Detection of adventitious agents is performed by quality control tests. In these biological assays, another problem arises as fetal bovine serum (FBS) is used as an ingredient in tissue culture media. FBS contaminated with bovine viral diarrhea virus (BVDV) or other bovine pathogens, as well as antibodies against these pathogens may lead to false results in quality control assays.  In this study, in order to determine the actual status of commercial FBS, we performed quality tests on various FBS samples. As a result, in 28 of 49 FBS samples (57.1%), pestivirus genes were detected by pan-pestivirus reverse transcription-polymerase chain reaction assay. Furthermore, two samples contained infectious BVDV. Neutralizing antibodies against BVDVs were detected in 48 of 49 samples (97.6%) by the virus neutralization test based on the serum-dilution or virus-dilution methods. Antibodies against other bovine pathogens were detected rarely in these samples[The samples are contaminated with BVDV, the controls are contaminated with BVDV and other bovine pathogens are present too.]

June 2, 2011 – Early-Childhood Membranous Nephropathy Due to Cationic Bovine Serum Albumin “Eleven patients, including four children, had high levels of circulating anti–bovine serum albumin antibodies, of both the IgG1 and IgG4 subclasses. These patients also had elevated levels of circulating bovine serum albumin, without an increase in circulating immune complex levels. Some patients with childhood membranous nephropathy have both circulating bovine serum albumin and anti–bovine serum albumin antibodies. Bovine serum albumin is present in immune deposits,suggesting that cationic bovine serum albumin is pathogenic through binding to the anionic glomerular capillary wall.”    [According to MedLine Plus, from the NIH: “Membranous nephropathy is a kidney disorder that leads to inflammation and thickening of the kidney structures that filter wastes and fluids, leading to problems with kidney function. Thicker glomerular membranes do not work normally. Large amounts of protein are lost in the urine as a result. This condition is one of the most common causes of nephrotic syndrome. It may be a primary kidney disease, or it may be associated with other conditions.” Interesting that MedLine Plus also says: “The exact reason for this thickening is not known.”

August 2010 – The establishment of a highly sensitive ELISA for detecting bovine serum albumin (BSA) based on a specific pair of monoclonal antibodies (mAb) and its application in vaccine quality control. “A highly sensitive sandwich enzyme-linked immunosorbent assay (ELISA) for quantifying BSA was established, based on two mAbs that recognize different epitopes on a BSA molecule. Our ELISA system was used to detect BSA concentrations in several vaccines, such as the MMR (measles, mumps and rubella) vaccine, hepatitis A vaccine, and hepatitis B vaccine. Moreover, we compared the mAb ELISA and the present pAb ELISA by detecting BSA standards and bovine serum samples.” Comment: It appears that all vaccines made with bovine serum retain residual adventitious bovine viruses and most likely, albumen'''.

May 2010 – Human and animal vaccine contaminations “The introduction of new techniques of vaccine virus production on cell cultures has lead to safer vaccines, but has not completely removed the risk of virus contamination.” There are several examples of vaccine contamination, for example, contamination of human vaccines against poliomyelitis by SV40 virus from the use of monkey primary renal cells. These incidents have lead industry to change certain practices and regulatory authorities to develop more stringent and detailed requirements. But the increasing number of target species for vaccines, the diversity of the origin of biological materials and the extremely high number of known and unknown viruses and their constant evolution represent a challenge to vaccine producers and regulatory authorities.

Comment: A 1999 a workshop co-sponsored by the FDA and the CBER named'''Evolving Scientific and Regulatory Perspectives on Cell Substrates for Vaccine Development,” '''convened government and industry experts to discuss the problems surrounding vaccine contaminants. Researchers agreed that avian retroviruses and reverse transcriptase have long been detected in influenza vaccines and other vaccines made from eggs. What they did not agree upon, however, was the effects these extra viruses may be having on humans, including the possibility that they may be causing cancer. 'Some researchers considered the extra viruses to be completely benign. Called “free riders,” the animal viruses had not been found to interact with the immune system. However, other researchers cautioned that considering all contaminants to be benign had a glaring flaw: Even though many inactive viruses have been tested and are indeed harmless, not all viruses have been tested. If some viruses are found to have the ability to replicate, they could very well cause harm. Dr. Walid Heneine, a CDC virologist, publicly cautioned the importance of “not generalizing” that all accidental viruses are harmless. She sited research conducted by Weissmahr, et al. demonstrating that because certain viral contaminants were capable of replicating, they may be capable of causing harm. What’s coming through that needle could be deadly.

September 7, 2009 – Recommendations for the Use of Vaccines Manufactured with Bovine-Derived Materials “In 2000, CBER learned that its recommendations regarding the sourcing of bovine materials for the manufacture of vaccines had not been followed in at least one instance. As a result of this finding, CBER requested all vaccine manufacturers to review the source for all bovine-derived materials used in the manufacture of their vaccines. This review identified additional vaccines manufactured with bovine-derived materials that had been obtained from European countries on the USDA list.” [CBER is the Center for Biologics Evaluation and Research, a division of the FDA.]

Comment: CBER, the Center for Biologics Evaluation and Research, is a division of the FDA. Bovine calf serum is used for the production of the following vaccines: rubella, chickenpox, polio, Prevnar, and the adult pneumonia shot. Nearly 100 percent of this commercially available serum obtained from cows is contaminated with bovine viruses. Are we incorporating chicken and cow genetic material into the human genome? Are we altering the genes of future generations in unknown ways through vaccines?

June 18, 2009 – Bovine Derived Materials Used in Vaccine Manufacturing Questions and Answers  Comment: This is the FDA answer and explanation for using bovine products in the production of vaccines.

June 18, 2009 – Vaccines and Variant CJD (vCJD) Questions and Answers “This is the report of the meeting of the FDA Transmissible Spongiform Encephalopathy Advisory Committee (TSEAC) and the Vaccines and Related Biological Products Advisory Committee (VRBPAC).

June 12, 2009 – 21st meeting of the Transmissible Encephalopathy Spongiform Encephalopathies Advisory Committee(pdf) “In the warning section for all plasma derivative products and other products such as vaccines that contain plasma derivatives like albumin''', it states because this product is made from human blood it carries a risk of transmitting infectious agents, e.g. viruses and, theoretically the CJD agent. The statement was intended to capture the uncertain but still possible risk.”

July 27, 2006 
– Outlook for the Implementation of a Human-Bovine (UK) Rotavirus Reassortant Vaccine (pdf) [Powerpoint presentation discussing a rotavirus vaccine developed from bovine serum.]

2006 – TSE risk assessment for starting materials used during, or in the manufacture of vaccines for human use–a consultant’s view of the commercial approach. “Following the occurrence of BSE in cattle in three continents since 1986, the need to ensure the TSE safety of vaccines is vital. Various actions have been taken to ensure safety targets are reached.”

2006 – Detection of adventitious viruses in biologicals–a rare occurrence “The most common detection scenarios include bovine viral diarrhea virus (BVDV) in fetal bovine serum samples, porcine parvovirus in porcine (pig) substrates, and murine minute virus, REO virus, and Cache Valley virus in Chinese hamster cell-derived bulk harvests. The two last-named viral entities are believed to be introduced via bovine serum used during the manufacturing process.”

2006 – WHO guidelines on tissue infectivity distribution in transmissible spongiform encephalopathies. (pdf)

January 2005 – Inactivated Poliomyelitis Vaccine(Diploid Cell Origin) “Since the polio vaccine (IPV) contains trace amounts of bovine serum albumin and may contain trace amounts of polymyxin B and neomycin, the possibility of allergic reactions in individuals sensitive to these substances should be borne in mind when considering the use of this vaccine.”

December 2004 – Vaccine Cell Substrates 2004  [Long list of presentations about cell line research]

April 24-26, 2004 – Enteric Vaccines for Pediatric Use” Workshop Report Airlie Center, Warrenton, VA

April 1, 2003 – Avoiding allergic reactions to childhood vaccines (and what to do when they occur)  “The sheer number of recommended childhood immunizations makes it imperative that pediatricians be able to recognize and treat allergic reactions and identify those children in whom revaccination is contraindicated. “Stabilizers are added to vaccines to stabilize the vaccine antigen. Porcine gelatin is the stabilizer contained within MMR and its component vaccines and in varicella, viral influenza, yellow fever, Japanese encephalitis, and DTaP vaccines (Table 4). Patients reporting clinical gelatin allergy have usually reacted to the bovine gelatin contained in foods. These patients may be at risk of allergic reactions following administration of gelatin-containing vaccines. It is possible that many reactions previously attributed to egg allergy in MMR recipients were due to gelatin allergy. IgE antibodies to gelatin were detected in 93% of patients reporting anaphylaxis to the monovalent measles, mumps, and rubella vaccines in Japan.”

January 2003 – NIAID Biodefense Research Agenda for Category B and C Priority Pathogens (pdf) “A spontaneous mutant has been used effectively in the field as a vaccine, but it can undergo reversion to virulence." Comment: This documents that viruses that have been attenuated (weakened) to be used in vaccines can revert to their full virulence, and with that, the ability to cause active disease. (see page 12 of the document under VACCINES."

June 2002 – Neurological adverse events associated with vaccination. “The present review summarizes data on neurologic complications following vaccination, and provides evidence that indicates whether they were directly associated with the vaccines. These complications include autism (measles vaccine), multiple sclerosis (hepatitis B vaccine), meningoencephalitis (Japanese encephalitis vaccine), Guillain-Barré syndrome and giant cell arteritis (influenza vaccine), and reactions after exposure to animal rabies vaccineSeizures and hypotonic/hyporesponsive episodes following pertussis vaccination and potential risks associated with varicella vaccination, as well as vaccine-associated paralytic poliomyelitis following oral poliovirus vaccination, are also described. In addition, claims that complications are caused by adjuvants, preservatives and contaminants [i.e. macrophagic myofasciitis (aluminium), neurotoxicity (thimerosal), and new variant Creutzfeldt-Jakob disease (bovine-derived materials)] are discussed.

March 20, 2001 – What Is the Risk of CJD From the Administration of a Vaccine? (free registration)

December 22, 2000 – Notice to Readers: Public Health Service Recommendations for the Use of Vaccines Manufactured with Bovine-Derived Materials

March 2000 – Evaluation of vaccines, interferons and cell substrates for pestivirus contamination.

June 17, 1999 – Note for Guidance for Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Veterinary Medicinal Products (pdf) “Iatrogenic transmission of spongiform encephalopathies has been reported. In sheep, scrapie has been accidentally transmitted by the use of Louping III vaccines prepared from pooled, formaldehyde treated bovine brain and spleen in which material from scrapie infected sheep had been inadvertently incorporated. In man, cases of transmission of CJD have been reported which have been attributed to the repeated parenteral administration of growth hormone and gonadotropin derived from human cadaveric pituitary glands. Cases of CJD have also been attributed to the use of contaminated instruments in brain surgery and with the transplantation of human meninges and cornea.

1999 – Bovine sera used in the manufacture of biologicals: current concerns and policies of the U.S. Food and Drug Administration regarding the transmissible spongiform encephalopathies.

November 1998 – Collective experiences of adventitious viruses of animal-derived raw materials and what can be done about them “Contamination of animal-derived raw materials with viruses, mycoplasmas, bacteria and fungi is common. These contaminants can interfere with the diagnosis of viral infection, and vaccines produced using infected cell cultures could lead to seroconversion or disease in the vaccinated animal. The purity, safety and efficacy of viral vaccines requires testing of the ingredients, cell substrates and final product. Methods for detection of viruses, especially bovine viral diarrhea virus, in nutrient serum, cell cultures, seed viruses and viral vaccines, and the frequency of their detection at the Center for Veterinary Biologics are discussed.”

July 1987 – A sandwich ELISA for bovine serum in viral vaccines.

August 19, 1985 – Pertussis toxin is required for pertussis vaccine encephalopathy (pdf) “Susceptibility to encephalopathy maps to genes of the major histocompatibility complex and correlates as well with the genetic regulation of the level of antibody response to bovine serum albumin.”

November 11, 1967 – Further experience of reactions, especially of a cerebral nature, in conjunction with triple vaccination: a study based on vaccinations in Sweden 1959-65. (full text)  “Case 2.-This child was healthy and of normal development. There was no reaction after the first injection. The patient had a convulsive attack, and a temperature of 39.5′ C. on the ninth day after the second injection at the age of 7 months. Next day there was a new attack-clonic on the right side-followed by paralysis. Lumbar puncture revealed albumin 34 mg./100 ml. and 2 cells. On the following day there were similar convulsions and paralysis, and complete loss of contact. E.E.G. showed incessant paroxysmal activity over the entire left hemisphere.

Pestivirus

Pestivirus is a virus that infects cattle. About 70% of herds are actively infected and can cause a variety of diseases, some not apparent until well after the initial spread of the virus in a herd. Pestviruses can infect humans through vaccines cultured using contaminated bovine serum. The most commonly detected pestiviruses in vaccines are bovine diarrhea virus 1 (BVDV-1) and bovine diarrhea virus 2 (BVDV-2).

Vaccines that use bovine serum:

  • All DTaP vaccines: Infanrix, Kinrix, Pediarix, Pentacel
  • Teen Tdap vaccines: Adacel, Boostrix
  • Tetanus boosters: DT, dT, TT (no longer readily available)
  • Hepatitis A
  • Polio
  • ProQuad – (MMR + V)
  • Japanese Encephalitis
  • MMR
  • Rotateq
  • Rabies
  • Varivax and
  • Zostavax (shingles vaccine).

July 2011 – Methods to select suitable fetal bovine serum for use in quality control assays for the detection of adventitious viruses from biological products. “In this study, in order to determine the actual status of commercial fetal bovine serum (FBS), we performed quality tests on various samples. As a result, in 28 of 49 FBS samples (57.1%), pestivirus genes were detected. Furthermore, two samples contained infectious BVDV. Neutralizing antibodies against BVDVs were detected in 48 of 49 samples (97.6%) by the virus neutralization test based on the serum-dilution or virus-dilution methods.” Comment: Virtually 100% of all bovine serum used in the manufacture of vaccines and other human products re contaminated with bovine (cow) viruses.

June 2008 – Simple procedures to obtain exogenous internal controls for use in RT-PCR detection of bovine pestiviruses. The pestiviruses that are able to infect bovines are mainly Bovine Viral Diarrhea Virus 1 (BVDV 1) and Bovine Viral Diarrhea 2 (BVDV 2). Bovine pestiviruses are ubiquitous pathogens in herds and frequent contaminants of biologicals. Despite continuous surveillance, these agents have been detected in cell lines, fetal bovine serum, live and inactivated animal and human vaccines and interferon for human use. Risk for animals is evident and inoculation can occur when contaminated veterinary products are used, for instance, but attention should also be directed towards human health. The virus has been detected in preparations of human leucocytes. Furthermore, it has been suggested that pestiviruses might be related to [human] infantile gastroenteritis and microencephaly. Since the virus is a frequent contaminant in fetal bovine serum, risk of contamination is high in most laboratories.

April 26, 2004 – Homologous recombination in bovine pestiviruses Phylogenetic and statistic evidence

2004 – Genotypes of Pestivirus RNA detected in anti-influenza virus vaccines for human use. “Nine polyvalent human influenza virus vaccines were tested by reverse transcriptase-polymerase chain reaction (RT-PCR) for the presence of pestivirus RNA. Samples were selected from manufacturers in Europe and the USA. Three samples of the nine vaccines tested (33.3%) gave positive results for pestivirus RNA.”

December 2002 – Detection and characterization of pestivirus contaminations in human live viral vaccines. “Thirty-six lots of human live viral vaccines produced by three manufacturers were tested for the presence of pestiviruses. Bovine viral diarrhea virus (BVDV) RNA was detected in 33% of the vaccine lots. All positive results were caused by the mumps component of a single manufacturer…All attempts to detect virus antigen in MRC-5 human diploid cells or to infect these cells with BVDV failed. This suggests that BVDV RNA detected in human live viral vaccines represents passive carry over of BVDV from contaminated fetal calf serum (FCS) rather than active virus replication in human diploid cells.”

October 11, 2002 – Vaccines and Genetic Mutation (full text by Dr. Harold Buttrum)

2001 – Genotypes of pestivirus RNA detected in live virus vaccines for human use “Live virus vaccines for human use, 29 monovalent vaccines against measles, mumps, rubella or polio, 8 polyvalent vaccines against measles-mumps-rubella and 1 bacterial polyvalent vaccine against Streptococcus pneumoniae, were tested by reverse transcriptase-nested PCR for the presence of petivirus or pestivirus RNA. Twenty-four samples were selected from European manufacturers, ten were from U.S.A. and four from Japan. Five (13.1%) out of 38 tested samples were positive for pestivirus RNA…These findings indicate that contamination by animal pestivirus can occur in biological products for human use.”

March 2000 – Evaluation of vaccines, interferons and cell substrates for pestivirus contamination.  “Cell lines commonly used to produce biological products and vaccines were experimentally infected with the NADL strain of BVDV to determine if they were permissive for virus replication. MRC-5 and WI-38 cells were not infected. In contrast, VERO, CHO and CEF cells showed evidence of pestivirus infection. Taken together these data suggested that currently licensed viral vaccines were unlikely to be contaminated with pestiviruses. However, cell banks derived from non-human primate, hamster or rabbit kidney cell lines, or cultures of primary chick embryo fibroblasts, may be infected with BVDV if exposed to pestivirus contaminated raw materials during manufacture.”

2000 – What Is Coming Through That Needle? The Problem of Pathogenic Vaccine Contamination  by Benjamin McReardon. “In recent times mankind is experiencing a situation never previously encountered, that being the threat of release of pathogens intended to kill or disable large numbers of people. That danger has prompted certain health agencies to prepare for possible mass vaccination of the populace… for humans, pets, and agricultural animals.  You do owe it to yourself to be informed.”

April 1997 – Molecular characterization of ovine (sheep) pestiviruses.  “The results demonstrated that sheep may naturally be infected not only with border disease virus (BDV), but also with bovine viral diarrhoea virus (BVDV) types I and II.”

December 1996 – Application of PCR for detection of mycoplasma DNA and pestivirus RNA in human live viral vaccines.  “PCR techniques were applied for the detection of mycoplasma DNA and pestivirus RNA to 43 lots of live viral vaccines (measles, mumps, rubella, and oral poliomyelitis') produced by six manufacturers in Japan. Although mycoplasma DNA was not detected in any of the vaccines tested, pestivirus RNA was detected in 12 lots (28%).'''The incidence of contamination among the four viral vaccines was in the range of 20 to 37%''', and the incidence among the six manufacturers varied from 0 to 56%.”

1995: Demonstration and genotyping of pestivirus RNA from mammalian cell lines. “We examined 20 cell lines of various animal origins for the presence of pestivirus contamination by the reverse transcription-polymerase chain reaction (RT-PCR), and found 15 (75%) cell lines were positive… Bovine cell lines tested were all contaminated with genotypes I, II, or III of bovine diarrhea virus (BVDV). Cell lines of canine, feline, and primate origin were contaminated with genotype II of BVDV. Cell line Ch1Es of caprine origin was contaminated with border disease virus (BDV).”

January 1995 – Adventitious pestivirus RNA in live virus vaccines against bovine and swine diseases.

February 7, 1994 – Evidence of Pestivirus RNA in Human Virus Vaccines (pdf) – We examined live virus vaccines against measles, mumps, and rubella for the presence of pestivirus RNA or of pestiviruses by reverse transcription PCR. Pestivirus RNA was detected in two measles-mumps-rubella combined vaccines and in two monovalent vaccines against mumps and rubella'''. Nucleotide sequence analysis of the PCR products indicated that a modified live vaccine strain used for immunization of cattle against bovine viral diarrhea is not responsible for the contamination of the vaccines.”

1994 – Comparative analysis of the 5′ non-coding region of pestivirus RNA detected from live virus vaccines.