The skinny on real vaccine issues

The following collection of medical journal abstracts demonstrates a variety of vaccine problems: actual reports of vaccine contamination by microorganisms, difficulties in the assessment of vaccine safety given the statistical methods employed by FDA/CDC, limitations in testing procedures, cancers and autoimmunity which are clearly shown to be consequences of vaccination. Other issues of interest are also discussed. For copyright reasons, I cannot post the full text of these articles. The collection should be of particular interest to those involved in oversight of vaccines, as it offers a theoretical framework for understanding various problems encountered in clinical practice.


For me, a collector of anecdotes of hundreds of vaccine problems, it provides an explanation of why so many bleeding problems are reported, why so many are experiencing thyroid dysfunction, and how to assess vaccines in the laboratory (by using newer methods than currently employed, by animal testing for many types of autoimmunity, fertility and neoplasm, by search for contamination by microorganisms, for example).


The comments in red below are my own, providing a quick summary of what is most germane in each article.

Use of formaldehyde to kill residual microorganisms in vaccines has not always been successful, allowing for live contaminants:


Brown F (ed): Virological Safety Aspects of Plasma Derivatives. Dev. Biol Stand. Basel. Karger. 1993. vol SI, pp 103-107

U.S.D.A. Plum Island Animal Disease Center, P.O. Box 848. Greenport, NY 11944-0848, USA



F. Brown


Inactivation of viruses and bacterial toxins with formaldehyde for Ibc preparation of vaccines has been a favourite method for most of this century. The Cutter incident in 1955 with poliovaccine focussed attention on the problems accompanying the procedure for inactivating viruses although it had been known since the 1930s that the method was not without its dangers. It had also been known since about the same time that foot-and-mouth disease vaccines prepared in this wav could carry residual infectivity. The molecular methods of analysis introduced in the 1970s proved without any doubt that the outbreaks in France in 1981 and in other countries of Western Europe in the 1980s were caused by improperly inactivated vaccines. Recent molecular evidence has now shown that formaldehyde-inactivated Venezuelan equine encephalitis vaccines were the probable cause of the outbreaks of the disease during the 1969-1972 pandemic in Central America. In the author's opinion it is remarkable that formaldehyde is still used for the preparation of inactivated vaccines, particularly since it is known that the procedure also affects the immunogenic epitopes of the viruses.

Because there have not been well-established standards of how to establish vaccine stability over time and under varying environmental conditions, an international conference was held to begin to create such standards internationally. Note that Bioport did not perform stability evaluations of their stored vaccines until 1997, and I am not sure the procedures they finally established were validated, nor whether they were used on vaccine produced prior to 1997.

Brown F (ed): New Approaches to Stabilisation ol Vaccines Potency. Dev Biol Stand. Basel. Kargcr. 1996. vol 87 pp 3(}9-318

Stability Testing Requirements for Vaccines- Draft Guidelines of the International Conference on Harmonization

M. Haase

PauI-Ehrlich-lnstitut, Langen, Germany

Abstract: The International Conference on Harmonisation (ICH) process considers ways in which the technical requirements for assuring the quality, safety and efficacy of medicines can be made more compatible. At present, divergencies can make it necessary for companies to repeat tests or present the data in different formats to satisfy the requirements of different health authorities, tn this context, I report that agreement on Step 2 of an ICH guideline on stability testing of biotechnological/biological products has been reached. This guideline will be of significant benefit in reducing the need to repeat costly and lengthy storage trials for biologicals to meet differing requirements. This guideline will be an annex to the ICH Harmonized Tripartite Guideline on Stability Testing of New Drug Substances and Products published in 1993. According to its present scope it covers vaccines consisting of well-characterized proteins and polypeptides and conventional vaccines after consultation with the appropriate regulatory authorities. The purpose of stability studies is to establish how the quality of a drug substance (bulk material) and a drug product (final container product) varies with time under the influence of a variety of environmental factors such as temperature, humidity and light, and enables recommended storage conditions, re-test periods and shelf lives to be established. The guideline contains specific advice for the selection of batches, the stability-indicating profile, storage conditions, testinq frequency, test procedures and test criteria, specifications, long term -, stress - and accelerated testing, labelling, etc. and a glossary which defines certain of the traditional terms used in the biologics field. Therefore, it will help in informing the industry and the regulatory authorities of the important factors in stability testing of biological/biotechnological products.

Note that the principal toxicology methods employed to test the safety of vaccines are over 40 years old, and ignore advances in immunotoxicology and molecular biology. The anthrax vaccine "safety test" involves simply injecting a small number of mice and guinea pigs with the vaccine and observing them for 7 days. If the animals do not lose weight or die, or show any major problems, the vaccine is pronounced safe.

Toxicology 119 (1997) 95-101

Issues with introducing new immunotoxicology methods into

the safety assessment of pharmaceuticals

Jack H. Dean

Sanqfi Research Dirision, Sanoff PharmaceuticaLs, Inc'., P.O. Bo-~ 3026, 9 Great Va//e)' Parkway, Maitern, PA 19355, USA


Unfortunately, the principal routine toxicology methods employed for the safety assessment of new products are over 40 years old and rely primarily on histopathological evaluation. It is difficult to introduce newer immunotoxicol-ogy or molecular toxicology methods into toxicity assessment without extensive and time consuming validation requiring several years due to concern for standardization of methods, inter-laboratory replication of these methods and resistance to acceptance of new methods by both regulatory agencies and industry. During the past 15 years, significant progress has occurred in the fields of molecular biology and basic/clinical immunology which promoted the establishment of newer more sensitive methods to assess cell injury or immune system effects in humans and laboratory animals. This brings us to the challenges associated with trying to introduce new immunotoxicology or molecular toxicology methods into the safety assessment of new products. Our experience at Sanoff Research with immunotoxicity methods development or validation and approaches for molecular toxicology and their application to the preclinical development of new chemical drug entities (NCE) will be discussed. Laboratories to investigate immunotoxicity and molecular toxicology were established during the past 10 years among several industrial research groups for the evaluation of new chemicals and drug candidates. Immunotoxicology methods have been selected and optimized for rodent testing leading to four inter-laboratory collaborative studies to demonstrate the reproducibility and value of these methods for predicting toxicity. Our experience at Sanoff has led us to believe that these newer methods can represent an important part of drug development, should be applied on an as needed basis, and should be driven by data suggestive of an immune or molecular toxicology effect or by the class of the chemical being evaluated. Ex vivo and in vitro assays are selected from a menu of validated methods for application on a case-by-case basis. Results in this area with inter-laboratory validation of these methods will be discussed. Newer molecular toxicology and immunotoxicity methods are beginning to play a more important role in the safety evaluation and risk assessment process. © 1997 Elsevier Science Ireland Ltd.

Keywords: Safety assessment; Immunotoxicology; New chemical entities; Pharmaceuticals; Inter-laboratory replication; Validation

This study demonstrated that immunized calves had INCREASED susceptibility to infection after vaccination than non-immunized calves. Occasionally, vaccination may actually impair specific immunity to a pathogen.

Am J Vet Res 41, #11 Nov 1980 1773-8

Response of Calves to Lung Challenge Exposure with Pasteurella haemolytica After Parenteral or Pulmonary Immunization

B.N. Wilkie, DVM, PhD; R. J. ?. Markham, BSc, PhD; P. E. Shewen, BSc, DVM, MSc


In 3 experiments, calves were vaccinated by intrabronchial or subcutaneous injection of formalinized Pasteurella haemo!ytica. Immunization was evaluated by assessing the clinical and pathologic responses to pulmonary challenge exposure with live homologous bacteria. Serum and bron-choalveolar washings were titrated for antibody by indirect antiglobulin) bacterial agglutination.

Response to challenge exposure was determined by increased rectal temperature and faster respiratory rate. In all experiments, the most obvious clinical change occurred in challenge-exposed calves which had been vaccinated by the subcutaneous injection of killed P haemolytica with added adjuvant. Also, macroscopic pulmonic lesions were ~corded most frequently in calves vaccinated by this route. In alt instances, immunization resulted in elevated anti-P haernolytica titers both in lung and serum.

From p. 716-717 "…adverse vaccine reactions typically include fever, stiffness, sore joints and abdominal tenderness, susceptibility to infections, neurologic disorders and encephalitis, collapse with agglutinated red blood cells and icterus (autoimmune hemolytic anemia) (immune-mediated thrombocytopenia). Liver enzymes may be markedly elevated, and liver or kidney failure may ioccur by itself or accompany bone marrow suppression. Furthermore, MLV vaccination has been associated with the development of transient seizures in…dogs….susceptible to immune-mediated diseases, especially those of hematologic or endocrine tissues (e.g. AIHA, ITP, autoimmune thyroiditis). Postvaccinal polyneuropathy is a recognized entity associated occasionally with the use of distemper, parvovirus, rabies and presumably other vaccines."


Most of the problems mentioned in the preceding paragraph have been reported to occur, anecdotally, in humans receiving the anthrax vaccine.



More Bumps on the Vaccine Road


Hemopet, 938 Stanford Street, Santa Monica, CA 90403

I. Introduction and Background

II. Overview of Adverse Effects of Vaccines

III. Breed Study Examples

    1. Vaccine-Associated Disease in ()Id English Sheepdogs
    2. Vaccine-Associated Disease in a Family of Young Akitas
    3. Vaccine-Associated Disease in Young Weimaraners

IV. Periodicity of Booster Vaccination

V. Alternative Strategies to Conventional Vaccination

A. Monitoring Serum Antibody Titers

B. Reducing the Number of Vaccine Antigens Used or Given Simultaneously

C. Avoid Vaccinating or Overvaccinating Certain Populations

D. Alternative Methodologies

VI. Summary and Future Directions


Drs. Nicholson have long proposed that mycoplasma cause or contribute to illness in patients with Gulf War illness and chronic fatigue syndrome. Vaccine contamination by mycoplasma appears to have been a frequent occurrence in veterinary vaccines; it may be a problem in human vaccines as well. I am unaware of any published literature that reported a search for such contaminants in human vaccines. Although there is no evidence that anyone has looked for mycoplasma in childhood or other human vaccines, the absence of research does not mean such contamination does not exist.

VACCINE, Vol. 4, Dec. 1986, 237-40

A survey of mycoplasm detection in

Veterinary vaccines

Denise H. Thornton

Nine live virus veterinary vaccines from six sources were found to be contaminated with myeoplasma. The vaccines were for use in canine, feline and avian species, and 53 batches of the products were at fault. The isolates were identified as Mycoplasma hominis, M. arginini, M. orale, M. hyorhinis and M. gailinarum. Investigation of the contamination rate of other batches or otherproducts from the same source in some cases helped to determine the source of infection. Mycoplasma contaminants can be considered important not only because of their role as pathogens but also because they may indicate that insufficient care has been taken during vaccine manufacture or quality control.

Keywords: Contaminants: mycoplasma; veterinary vaccines

This very balanced article looks at all the angles in the decision to vaccinate, including cost, tumor induction, encephalitis, immune-mediated diseases, vaccine failures and the #1 issue: Risk versus Benefit.

Journal of the American Veterinary Medical Association, Vol. 207, # 4, Aug. 15, 1995, 421-5

Current Concepts

Are we vaccinating too much?

Concerns about vaccine reactions have left veterinarians and pet owners wondering about the best vaccination schedules for dogs and cats. There is little scientific documentation that backs up label claims for annual administration of most vaccines. Although it is possible that some vaccines work best when given annually, others need to be given more often, and many others may last for years. The only vaccine routinely tested for minimum duration of immunity is the rabies vaccine.

The evidence for tumors that develop at the sites of vaccination.

Journal of the American Veterinary Medical Association, Vol. 203, #3, Aug. 1, 1993, 396-405


Epidemiologic evidence for a causal relation between vaccination and fibrosarcoma tumorigenesis in cats

Philip H. Kass, DVM, PhD; William G. Barnes Jr., DVM; W. L. Spangler, DVM, PhD;

Bruno B. Chornel, DVM, PhD; M. R. Culbertson, DVM, PhD

Summary: Within the past 2 years, a putative causal relationship has been reported between vaccination against rabies and the development of fibrosarcomas at injection sites in cats. A retrospective study was undertaken, involving 345 cats with fibrosarcomas diagnosed between January 1991 and May 1992, to assess the causal hypothesis. Cats with fibrosarcomas developing at body locations where vaccines are typically administered (n = 185) were compared with controls (n = 160) havingfibrosarcomas at locations not typically used for vaccination. In cats receiving FeLV vaccination within 2 years of tumorigenesis, the time between vaccination and tumor development was significantly (P = 0.005) shorter for tumors developing at sites where vaccines are typically administered than for tumors at other sites. Univariate analysis, adjusted for age, revealed associations between FeLV vaccination (odds ratio [oR] = 2.82; 95% confidence interval icl] = 1.54 to 5.15), rabies vaccination at the cervical/interscapular region (oR --- 2.09; 95% cl = 1.01 to 4.31), and rabies vaccination at the femoral region (oR = 1.83; 95% cl--- 0.65 to 5.10) with fibrosar-coma development at the vaccination site within 1 year of vaccination. Multivariate analysis, adjusted for age and other vaccines, also revealed increased risks after FeLV (oR = 5.49; 95% ˘I = 1.98 to 15.24) and rabies (oR = i .99; 95% cz = O. 72 to 5.54) vaccination. The risk of cats developingfibrosarcoma from a single vaccination in the cervical/interscapular region was almost 50% higher than in cats not receiving vaccines at that site; the risk in cats with 2 vaccinations was approximately 127% higher and the risk with 3 or 4 vaccines was approximately 175% higher. However. the frequency of fibrosarcomas in the population is low (estimated at 20/100,000 cats). In approximately half of the cats in our study, fibrosarcomas were at sites where vaccines conventionally are given, and of those cats, approximately half (depending on vaccine) had previously received a vaccine at the tumor site. Although we believe that veterinarians should not alter their vaccination protocols, precautions in vaccine administration (administering different vaccines at varied sites) and further informed consent (presenting current information in a proper benefit/risk context) appear to be advisable.

Yes, vaccines do cause autoimmune illness, and here is the evidence, in detail.
  Advances in Veterinary Medicine, Vol. 41, 1999, 733-47

Vaccine-Induced Autoimmunity in the Dog


Departments of Veterinary Pathobiologky and Veterinary Clinical Science.s,

Purdue University West Lafayette, Indiana 47.907

I. Introduction

II. Materials and Methods

A. Animals

B. Vaccination Schedule C. Viral Serology D. Hematology E. Endocrinology F. Immunology

G. Lymphocyte Blastogenesis Assay

H. Enzyme-Linked hnmunosorbent Assay (ELISA }

I. Necropsy

J. Statistical Analysis

III. Results

A. Viral Serology

B. Clinical Observations, Hematology, and Endocrinology C. Immunology D. Necropsy

IV. Discussion Acknowledgments References

The FDA and CDC admit how difficult it can be to assure the safety of vaccines.

Public Health Reports, Jan./Feb. 1997, Vol. 112, 10-20

The Complicated Task of Monitoring VACCINE SAFETY

By Dr. Susan S. Ellenberg, PhD and Robert T. Cohen, MD MA


VACCINATION IS AN ESSENTIAL component of modern public health programs and is among our most cost-effective medical interventions. Yet despite vaccines' clear effectiveness in reducing risks of diseases that previously attacked large proportions of the population, caused many deaths, and left many people with permanent disabilities, current vaccination policies are not without controversy. Vaccines, like all other pharmaceutical products, are not entirely risk-free; while most known side effects are minor and self-limitedl some vaccines have been associated with very rare but serious adverse effects. Because such rare effects are often not evident until vaccines come into widespread use, the Federal government maintains ongoing surveillance programs to monitor vaccine safety. The interpretation of data from such programs is complex and is associated with substantial uncertainty. A continual effort to monitor these data effectively and to develop more precise ways of assessing risks of vaccines is necessary to ensure public confidence in immunization programs.

Vaccines may interact to impair the expected immune response to a single vaccine. Has the DOD studied the interaction of many vaccines given simultaneously, as is done in boot camp and prior to certain deployments? The practice of multiple simultaneous vaccination should be halted unless evidence is obtained that the process is without additional risk of adverse reactions, and that immunity occurs at levels appropriate to individual vaccinations.
  Canadian Journal of Veterinary Research, Vol. 53, 154-60

Effects of Vaccines on the Canine Immune System

Tom R. Phillips, Jean L. Jensen, Michael J. Rubino, Wen C. Yang and Ronaid D. Schultz


The effects of several commercially available polyvalent canine vaccines on the immune system of the dog were examined. The results demonstrated that the polyvalent vaccines used in this study significantly suppressed the absolute lymphocyte count and that most of the polyvalent vaccines significantly suppressed lymphocyte response to mitogen, but had no effect on natural effector cell activity, neutrophil chemiluminescence, nor antibody response to canine distemper virus. The individual vaccine components from the polyval-ent vaccines when inoculated alone did not significantly suppress the lymphocyte response to mitogen. However, when canine distemper virus was combined with canine adenovirus type 1 or canine adenovirus type 2, significant suppression in lymphocyte responsiveness to mitogen occurred. The results indicate that interactions between canine distemper virus and canine adenovirus type I or canine adenovirus type 2 are responsible for the polyvalent vaccine induced suppression of lymphocyte responsiveness.

Again, a candid discussion of the limitations of those tests commonly used to evaluate vaccine contamination by microorganisms.

Rev. sci. tech. Office international Epizootics. 1995, 14 (4), 1073-1082


Biologicals: test procedures available to assess components and products, with limitations


A.M.T. LEE *


Summary: Contamination with a pathogen, residual live organisms in inactivated products, and a lack of safety of live products may be considered to constitute the greatest risks associated with the use and the international movement of biological products. Although tests are conducted to monitor the risks, the limitations of such tests must be recognised and steps should always be taken to minimise and, as far as possible, avoid the risk. Tests must be suitably sensitive and specific for their function, but they must also be practical and reproducible. Studies on the sensitivity of tests provide a measure of their limitation;

The author describes points to consider for the assessment of' the suitability of different test methods. Emphasis is placed on tests for parameters associated with risk, such as extraneous agent testing. Examples of such analyses are discussed. There is a need for an exchange of information and a scientific debate on such issues if international acceptance of test methods arid harmonisation of requirements are to be achieved.


KEYWORDS: Diagnostic products - Extraneous agents - Inactivation -Risk - Safety - Tests - Vaccines.