Presentation Highlights – Anthrax Vaccine

1. Presentation Highlights – Anthrax Vaccine Note from Randi: **Quote from brief:  " The anthrax vaccine is causing massive damage." **Slide 21 shows that Anthrax Vaccine presents 600 times the adverse reaction rate for joint disease as compared to "Td" (Tetanus and diphtheria toxoid). **Slide 23 shows that Anthrax Vaccine present 24 times the adverse reaction rate for gastrointestinal problems compared to Tetanus toxoid. **Slide 25 shows that Anthrax Vaccine present 250 times the adverse reaction rate for abnormal liver function as compared to Tetanus toxoid. **Slide 32 - Conclusions - Safety: **"In evaluating anthrax vaccine it has a safety profile significant worse than almost any civilian vaccine." **And "Anthrax vaccine is associated with a series of serious adverse events that can significantly impact multiple organ systems within the body, and result in permanent disability." **And "Anthrax vaccine contains a significant toxins combined with an aluminum adjuvant that may work synergistically to produce temporally related adverse reactions in susceptible vaccine recipients" **Slide 33 - Conclusions - Efficacy: **"Efficacy of anthrax vaccine is based on several studies in animals, and has never been tested in a double-blind placebo controlled human vaccine trial." **"The only study conducted in humans using anthrax vaccine was published in 1962 of an adjuvant controlled, single-blinded, clinical trial among mill workers using an alum-precipitated vaccine – a vaccine with a formulation different from the present anthrax vaccine.“ **Slide 34 "It must be noted that based upon this data the anthrax vaccine employed was not demonstrated to be statistically efficacious against inhalation anthrax."

2. Anthrax Vaccination:An Assessment of Potential Vaccine Safety Concerns by David A. Geier, B.A. Vice-President, The Institute of Chronic Illnesses & Mark R. Geier, M.D., Ph.D. President, The Genetic Centers of America Email: mgeier@comcast.net Copyright 2006

3. Anthrax Infection:

4. Causative agent: Bacillus anthracis (spore forming) • Zoonotic disease • Primarily infects wild and domestic animals (e.g. sheep, cattle, goats, camels, antelope and other herbivores). • Humans infected by exposure to infected animals, tissue of infected or, direct exposure to B. anthracis. • Routes of exposure • Cutaneous • Human skin contact with contaminated animal products. • Gastrointestinal • Ingestion of infected meat. • Inhalation • Aerosolized spores generated from industrial processing of infected animal products (e.g. hides, wool, hair). ** Person-to-Person transmission of anthrax has not been confirmed.

5. The Causative Agent: Anthrax Bacterium

6. Cutaneous Anthrax in Humans

7. Anthrax Toxins • Protective Antigen (PA) • An 82-kD portein that binds to receptors on mammalian cells and is critical to the ability of B. anthracis to cause disease. • Lethal Factor (LF) • A protease that inhibits mitogen activated protein kinase-kinase interaction. • Edema Factor (EF) • An adenylate cyclase that generates cyclic adenosine mono-phosphate in the cytoplasm of eukaryotic cells *** PA & LF form Lethal toxin. *** PA and EF form Edema toxin.

8. Symptoms & Incubation Period • Symptoms begin within 7 days of exposure. • The bacteria evades the immune system by producing an antiphagocytic capsules. • Spores infect macrophages, geminate, and proliferate. • Lethal toxin & Edema toxin are produced & cause necrosis and edema. • Toxemia progresses with bacteremia • Increased toxin production can cause widespread tissue destruction and organ failure.

9. Anthrax Vaccine:

10. Vaccine Manufacturer: BioPort Corporation (Lansing, Michigan) • Vaccine Components (per 0.5 mL dose) • Prepared from a cell-free filtrate of B. anthracis culture that contains no dead or live bacteria. • Strain used to prepare the vaccine is a toxigenic, nonencapsulated strain (V770-Np1-R). • Mixture of cellular products including PA (PA, LF, EF – all present at unknown levels). • 0.83 mg aluminum as an adjuvant • 0.0025% benzethonium chloride as a preservative • 0.0037% formaldehyde as a stabilizer

11. Vaccine Schedule • Primary vaccination consists of three subcutaneous injections at 0, 2, and 4 weeks. • Three booster vaccinations at 6, 12, and 18 months. • To maintain immunity the manufacturer recommends an annual booster injection.

12. Anthrax Vaccine

13. The Vaccine Adverse Event Reporting System (VAERS) database:

14. Established by an Act of the US Congress, jointly maintained by the CDC/FDA since 1990. • Presently, contains about 200,000 adverse event reports following administration of > 1 billion doses of vaccines to the US population. • The CDC has reported < 5% of all adverse event reports come from non-healthcare professionals. • Specific adverse events are required to be reported by law, and the FDA/CDC follow-up on specific serious adverse events. • Contains detailed information regarding those reporting adverse events, including: sex, age, onset time, geographic location, vaccine type (including manufacturer & lot information), adverse event information (coded into Costart Terms by VAERS staff), disability, death, hospitalization, emergency room visit, prior medical history, and laboratory test results.

15. Epidemiological Methods of Analysis • Case-Reports (descriptive) • Positive Re-challenge/Significant Exacerbation of Symptoms. • Case-Series (descriptive) • Focusing on information reported for a type of adverse event (i.e. onset time, male/female ratio, disabilities, vaccine type, etc.) • Vaccine Comparison Analysis (quantitative – estimate of the risk of reported adverse events) • Compare the incidence rate of adverse events reported to the VAERS database per net number of doses distributed/administered following one vaccine in comparison to another vaccine administered to a similar population.

16. Example Study I: * “Frequencies of adverse events were determined in children less than 7 years of age after any pertussis vaccination. We determined the number of all reports, fever, seizures, and reports of hospitalization within 72 hours after vaccination” * “The annual number of pertussis-containing vaccine doses administered during the period from 1991 to 1993 were estimated from Centers for Disease Control Biologics Surveillance.” * “Rates of adverse events were estimated as the number of vaccine adverse event reports divided by estimated doses administered.” * “The number of all VAERS reports, fever, seizure reports, and reports of hospitalization after DTP and DTaP vaccination are shown in Table 1. Rates of reporting of vaccine adverse events in this age group for each of the outcomes after DTaP were one third to one fourth those that occurred after DTP (P<.001).” Rosenthal S, Chen R, Hadler S. The safety of acellular pertussis vaccine vs whole-cell pertussis vaccine. Arch Pediatr Adolesc Med 1996;150:457-460. From the National Immunization Program, CDC, Atlanta, GA

17. Example Study II: * “To determine if the findings from the trials found would hold up on a larger scale, we compared the rate of reporting to the Vaccine Adverse Event Reporting System (VAERS), a passive reporting system, after either vaccine [Td or Tetanus Toxoid (TT)] from 1991 to 1997.” * “There were 40 reports per million doses of Td, and 27 reports per million doses of TT, for a reporting ratio of 1.4.” * “Reporting rates to VAERS are lower than the rates of VAEs [Vaccine-Associated Adverse Events] identified in the clinical trials, but the magnitude of the difference in VAEs following TT versus Td is similar.” Lloyd JC, Haber P, Mootrey GT, Braun MM, Rhodes PH, Chen RT, VAERS Working Group. Averse event reporting rates following tetanus-diphtheria and tetanus toxoid vaccinations: data from the Vaccine Adverse Even Reporting System (VAERS), 1991-1997. Vaccine 2003;21:3746-3750. From the National Immunization Program, CDC, & FDA

18. Conclusion I: * “The final comparison in VAERS between the 2 vaccines, while not perfectly precise, should still provide accurate relative qualitative and quantitative relationships. The validity of this comparison is strengthened by consistency between our results and safety data from clinical trials…” * “Controlled clinical trials, despite their admitted methodologic purity and elegance, are limited in sample size, duration, and population heterogeneity. Rare but serious adverse reactions or reactions in subpopulations can be detected only after product licensure and general use.” * “The Centers for Disease Control and Prevention and the Food and Drug Administration have established VAERS as the first line in such post-marketing surveillance.” Chen RT, Rosenthal S. An errant critique that misses the mark. Arch Pediatr Adolesc Med 1996;150:464-466. From the National Immunization Program, CDC, Atlanta, GA

19. Conclusion II: * “Chen et al. have reported that potential shortcomings, such as under-reporting, difficulty in determining causal relationship, and lack of precise denominators, should equally apply to both vaccines understudy in the VAERS employed in the technique developed by Rosenthal et al.” * “Of course, the real way to evaluate any database or method of analysis is to determine how results obtained compared with those obtained by using different methods of analysis in different databases.” * “In general, we have found that examining the VAERS database using the technique developed by Rosenthal et al. has had a very good positive predictive value in detecting real safety concerns with vaccines.” Geier DA, Geier MR. A Review of the Vaccine Adverse Event Reporting System database. Expert Opinion on Pharmacotherapy 2004;5:691-8.

20. Clinical & Experimental Rheumatology

23. Hepato-Gastroenterology

27. Given Dr. Geier’s significant knowledge of and experience with vaccines, he is qualified to testify as an expert on the issue of whether AVA caused Plaintiff’s condition. • Therefore, the Court finds Dr. Geier’s theory on general causation in this case has been subjected to sufficient peer review and publication to render it reliable. • Furthermore, reliance on the VAERS database to ascertain the risks associated with a given vaccine is generally accepted in the scientific community. Dr. Geier has published an article explaining this database and its use to evaluate vaccine safety concerns. In addition, Dr. Geier’s articles using the VAERS database to ascertain the relative risks of vaccines have been accepted by peer-reviewed scientific and medical journals. Also, this method has been used by other researchers, including those at the Center for Disease Control.

28. Case-Report of Anthrax Vaccine Adverse Reaction:

29. Captain ___ held a meeting on the fantail of the ___ on February 20, 2003. Captain __ informed all hands that they would be required to submit to the smallpox and the anthrax inoculations as this was now a requirement to sail on Military Sealift Command (MSC) ship. • Captain __ also stated that if any crew members refused the inoculations they would be logged and discharged for cause and the cost of repatriation would be at the crewmember’s own expense. • On February 23, 2003 in Suda Bay, Crete, Captain __ logged and discharged for cause two Steward’s Assistants for failure to take smallpox and anthrax inoculations.

30. February 21, 2003 at anchor at Suda Bay, Crete, crewmember __ received anthrax and smallpox vaccines. • Crewmember __ was given a small pamphlet about the smallpox vaccine and no information on the anthrax vaccine. • This and an AIDS test were all __ was given prior to the smallpox and anthrax vaccines. • In March 2003, one to two days before arrival in Charleston, South Carolina, __ was again required to receive a booster shot of anthrax vaccine. At this time __ got no information prior to the shot.

31. Since March of 2003 after __ was given the anthrax and the smallpox vaccinations, __ developed pain and numbness in legs and feet that have never gone away. • Doctors say ___ has permanent nerve damage. This damage makes him unsteady and causes him to fall from time to time. He needs assistance in bathing and generally cannot walk without assistance. • ___ uses a motorized scooter and walker to get around. ___ uses oxygen every day due to lung problems, secondary to pneumonia and pulmonary emboli, which ___ had in May of 2003. • Now __ has an oxygen bottle with him and a filter surgically implanted to prevent damage from emboli in the future. • ___ states that he is in pain most of the time and takes Neurontin (for the nerve damage), Percocet (for pain), and Cumadin (a blood thinner to prevent emboli). • Doctors say ___’s condition is probably permanent and ___ can never work at sea again. • Prior to the shots, ___ was healthy and able to work on a ship without any physical limitations.

32. Conclusion:

33. Anthrax Vaccine Safety Concerns: • In evaluating anthrax vaccine it has a safety profile significant worse than almost any civilian vaccine. • Anthrax vaccine is associated with a series of serious adverse events that can significantly impact multiple organ systems within the body, and result in permanent disability. • Anthrax vaccine contains a significant toxins combined with an aluminum adjuvant that may work synergistically to produce temporally related adverse reactions in susceptible vaccine recipients.

34. Anthrax Vaccine Efficacy Concerns: • Efficacy of anthrax vaccine is based on several studies in animals, and has never been tested in a double-blind placebo controlled human vaccine trial. • The only study conducted in humans using anthrax vaccine was published in 1962 of an adjuvant controlled, single-blinded, clinical trial among mill workers using an alum-precipitated vaccine – a vaccine with a formulation different from the present anthrax vaccine. • In this study, 379 employees received the vaccine, 414 received the placebo, and 340 received neither the vaccine nor the placebo.

35. It was reported that this documented a vaccine efficacy of 92.5% for protection against anthrax (cutaneous and inhalation combined), based on person time of occupational exposure. • Overall, five cases of inhalation anthrax occurred among persons who were either placebo recipients or did not participate in the controlled part of the study, whereas no cases occurred in anthrax vaccine recipients. • It must be noted that based upon this data the anthrax vaccine employed was not demonstrated to be statistically efficacious against inhalation anthrax.

36. From 1962 to 1974, based on information reported to the CDC, 27 cases of anthrax occurred in mill workers of those living near mills in the United States. • Of those, 24 cases occurred in unvaccinated individuals, one case of anthrax occurred after the person had been given one dose of anthrax vaccine. • Two cases of anthrax occurred after individuals had been given two doses of anthrax vaccine. • No documented cases of anthrax were reported for individuals who had received the recommended six doses of anthrax vaccine. • These individuals received an earlier version of a protective antigen-based anthrax vaccine.

37. Anthrax Vaccine Package Insert: • “BioThrax [anthrax vaccine] is indicated for the active immunization against Bacillus anthracis of individuals between 18 and 65 years of age who come in contact with animal products such as hides, hair or bones that come from anthrax endemic areas, and that may be contaminated with Bacillus anthracis spores. • BioThrax is also indicated for individuals at high risk of exposure to Bacillus anthracis spores such as veterinarians, laboratory workers and others whose occupations may involve handling potentially infected animals or other contaminated materials. • Since the risk of anthrax infection is the general population is low, routine immunization is not recommended”

38. Anthrax as a Biological Warfare Agent: • Transmission of B. anthracis spores to be transmitted by the respiratory route. • High mortality of inhalation anthrax. • WHO has estimated 50 Kg of B. anthracis released upwind of a population center of 500,000 people could result in 95,000 deaths and 125,000 hospitalizations. • Stability of B. anthracis spores vs other potential biological warfare agents.

39. General Recommendations: • We believe that an anthrax vaccine with an improved safety profile is needed if it is to be used in populations, either military or civilian, that are not under imminent threat of attack by biological warfare agents. • Grave concerns exist regarding the potential efficacy of the current anthrax vaccine to protect against inhalation anthrax exposure. • Given the widespread use of anthrax vaccination, potential producers of biological weapons may seek to produce anthrax strains not neutralized by the current vaccine. • Clearly, anyone receiving anthrax vaccine needs to understand the potential risks and benefits of anthrax vaccine, and make an informed consent decision to be vaccinated (i.e. not having to face significant penalties if choosing not be vaccinated).