Anthrax vaccine
Encyclopedia
Anthrax vaccines are vaccine
s against the infectious disease
anthrax
. Anthrax is caused by the spore
-forming bacterium Bacillus anthracis
, that most commonly occurs in wild and domestic mammals. Anthrax also occurs in humans when they are exposed to infected animals, hides, or tissue from infected animals, or when they are directly exposed to B. anthracis. Depending on the route of infection, anthrax disease can occur in three forms: cutaneous, inhalational, and rarely, gastrointestinal.
, Anthrax Vaccine Adsorbed (AVA, trade name BioThrax), is produced by Emergent BioDefense Corporation, formerly known as BioPort Corporation in Lansing, Michigan
. The parent company of Emergent BioDefense is Emergent BioSolutions
of Rockville, Maryland. Both Emergent BioSolutions
and Porton International Group, Ltd., Porton Down
, UK, are controlled by Fuad El-Hibri
.
The anthrax vaccine is produced from culture filtrates of an avirulent, nonencapsulated strain known as V770-NP1-R. No living organisms are present in the vaccine. In the U.S., the principal purchasers of the vaccine are the Department of Defense
and Department of Health and Human Services. Ten million doses of the vaccine have been purchased for the U.S. Strategic National Stockpile
.
The anthrax vaccine was originally licensed in 1970 by the U.S. National Institutes of Health
(NIH) and in 1972 the U.S. Food and Drug Administration (FDA) took over responsibility for vaccine licensure and oversight. In 1997, the Clinton administration initiated the Anthrax Vaccine Immunization Program
, under which active U.S. service personnel were to be immunized with the vaccine. Much controversy has surrounded the program since its inception. Since vaccination was mandatory, a perception developed that the anthrax vaccine was unsafe, causing sometimes serious side effects. Mandatory vaccinations were halted due to an injunction which was put into place on October 27, 2004. The injunction cast questions about numerous substantive challenges regarding the anthrax vaccine in footnote #10, yet the procedural findings centered on FDA procedural issues, stating that additional public comment should have been sought before the FDA issued its Final Rule declaring the vaccine safe and effective in December 2003. The FDA's incomplete rulemaking from 1985 effectively rendered the anthrax vaccine program illegal. The basis was the never finalized FDA Proposed Rule. In that rulemaking the FDA published, but never finalized, a licensing rule for the anthrax vaccine in the Federal Register, which included an expert review panel's findings. Those findings included the fact that the "Anthrax vaccine efficacy against inhalation anthrax is not well documented," and that "No meaningful assessment of its value against inhalation anthrax is possible due to its low incidence," and that "The vaccine manufactured by the Michigan Department of Public Health has not been employed in a controlled field trial." On December 15, 2005, the FDA re-issued a Final Rule & Order on the license status of the anthrax vaccine.
After reviewing extensive scientific evidence, but failing to address a variety of substantive issues of safety and efficacy raised in the public comments, the FDA again determined that the vaccine is licensed for the prevention of anthrax, regardless of the route of exposure. On October 16, 2006, the Defense Department announced the reinstatement of mandatory anthrax vaccinations for more than 200,000 troops and defense contractors. Then another lawsuit was filed by the same attorneys as before, challenging the basis of the vaccine's license on scientific grounds. The vaccinations will be required for most military units and civilian contractors assigned to homeland bioterrorism defense or deployed in Iraq, Afghanistan or South Korea.
with Emergent BioSolutions
BioThrax AVA and BioThrax IM intramuscular injections in the deltoid is given at 0 and 4 weeks, with three vaccinations at 6, 12, and 18 months, followed by annual boosters.
As of December 2008, the new BioThrax IM for intramuscular injections in the deltoid was approved by the US FDA which changes the immunity initialization sequence from 6 to 5 shots given at 0 and 4 weeks and then at 6, 12, and 18 months, followed by annual boosters. This prolonged initialization sequence is required with annual booster shots, because the anthrax vaccine's primary ingredient, the Anthrax Protective Antigen, can impair the life-cycle of the human immune system
's memory B-Cells and memory T-cells, through inducing the production of immunoglobulin G
(IgG) which sequesters furin
.
The loss of memory B-Cells leads to declining concentrations of IgG which can sequester APA, and therefore declining tolerance to the presence of anthrax bacteria. There is the potential that other memory B-Cell populations will be adversely affected as well.
Furin is the protein activator for pro-parathyroid hormone
, transforming growth factor beta 1, von Willebrand factor
, pro-albumin
, pro-beta-secretase
, membrane type-1 matrix metalloproteinase
, gonadotropin
, and nerve growth factor
. Furin is also essential to maintain peripheral immune tolerance by creating memory T-cells and suppressor T-cells.
Because IgG will cross the maternal fetoplacental blood-barrier, Furin-sequestering IgG can cause severe congenital birth defects during pregnancy.
The approved US FDA package insert for Anthrax Vaccine Adsorbed contains the following notice:
as an adjuvant
. Each dose of the vaccine contains no more than 0.83 mg aluminum per 0.5 mL dose. This is near the allowed upper limit of 0.85 mg/dose. The BioPort anthrax vaccine also contains 0.0025% benzethonium chloride
as a preservative, and 0.0037% formaldehyde
as a stabilizer.
In 2007, tests with mice of the anthrax vaccine using aluminum hydroxide adjuvant were reported as resulting in adverse neuropathy symptoms.
(CDC) reported that from 1990 to 2000, more than 1,859,000 doses of anthrax vaccine were distributed in the United States. During that decade, 1,544 adverse events
(.08% of total doses) were reported to the Vaccine Adverse Event Reporting System
(VAERS), 76 of these events (5%, 0.004% of total doses) were serious ("results in death, hospitalization, or permanent disability or is life-threatening"). Reports to VAERS are not necessarily events that have a cause and effect relationship, and the number of unreported adverse events caused by vaccines is unknown. These figures are intrinsically misleading in as much as the VAERS system is a passive system, meaning that an adverse event can only enter the system if the vaccinee or vaccinator take notice and report it. In other words, CDC cannot actively follow recipients of every dose of every vaccine to check for adverse events; its surveillance to a large extent has to rely on the vigilance and thoroughness of vaccine providers and recipients.
Although individuals have expressed health concerns after receiving anthrax vaccine, a congressionally directed study by the Institute of Medicine
(part of the National Academy of Sciences
) concluded that anthrax vaccine is as safe as other vaccines. The Academy considered more than a dozen studies using various scientific designs, and heard personally from many concerned US military service members.
Concern has been raised that the Pentagon
did not inform the United States Congress
about more than 20,000 hospitalizations involving troops who had received the anthrax vaccine, because "hospitalizations merely followed vaccinations in time, without documented proof of a cause-and-effect relationship." Independent researchers, David and Mark Geier, published "Anthrax vaccination and joint related adverse reactions in light of biological warfare scenarios" in Clinical and Experimental Rheumatology in 2002 vol. 20 page 119. They also published "Gastrointestinal adverse reactions following anthrax vaccination" in Hepatogastroenterology in 2004 vol. 51 page 762. The Geiers found a very large and statistically significant increase in joint symptoms and gastrointestinal problems following vaccination with anthrax vaccine. These authors concluded that due to the extreme reactogenicity of anthrax vaccine, its general use in the civilian population is undesirable. The safety of the U.S. anthrax vaccine continues to be an active area of study for both government and non-government personnel, but to date no data have been found that have caused the FDA to declare the vaccine anything other than safe and effective.
. Adverse multi-symptom illnesses were reported by a group of the volunteers. All were denied disability by the Defense Ministry. In February 2009, a petition from the disabled volunteers to disclose a report about Omer Two was filed with the Israel's High Court against the Defense Ministry, the Israel Institute for Biological Research
at Nes Tziona, the director, Avigdor Shafferman, and the IDF Medical Corps. Release of the information could support further action to provide disability compensation for the injured volunteers.
have undertaken a clinical trial to investigate more abbreviated vaccinations schedules for AVA. In addition, in 2004 the U.S. Department of Health and Human Services contracted with Vaxgen
Inc. to supply up to 75 million doses of a recombinant
anthrax vaccine, for $877 million. To be acceptable to HHS, this vaccine was to be protective against anthrax in three doses or less. On December 19, 2006, HHS voided the contract, because of stability problems with the vaccine, and a failure to start a Phase 2 clinical trial on time. In May 2008, Emergent Biosolutions, the Maryland-based successor to BioPort, both controlled by former Lebanese banker Faud el Hibri, acquired rights to Vaxgen's patents and processes.
Research is being done to develop and test new anthrax vaccines. One possible new type of vaccine would be administered by a skin patch rather than by injection.
Human Genome Sciences announced in 2007 the development of a new anthrax vaccine with the trademark name of ABthrax. The vaccine sensitizes the human immune system to the presence of the Anthrax Toxin Factor. In 2008, HGS reported on testing on 400 human volunteers given ABthrax. In 2009, HGS announced that they had made first delivery of 20,000 doses of ABthrax to the United States Department of Defense.
, is similar to that made in the U.S. The active ingredient in the vaccine is a sterile filtrate of an alum precipitated anthrax antigen from the Sterne strain in a solution for injection. The other ingredients are aluminium potassium sulphate, sodium chloride and purified water. The preservative is thiomersal (0.005%). The vaccine is given by intramuscular injection and the primary course of four single injections (three injections 3 weeks apart, followed by a 6 month dose) is followed by a single booster dose given once a year.
During Gulf War I, 1990–1991, the UK military were given the UK anthrax vaccine co-commitantly with the pertussis vaccine
as an adjuvant to improve the immune response efficacy of the UK anthrax vaccine.
announced that the Drugs Controller General of India (DGCI) had approved licensing of BioThrax AVA for distribution by Biological E. of Hyderabad.
preparedness, included emergency first responders such as police and firefighters, federal responders, medical practitioners, and private citizens. To that end, under the George W. Bush administration, the US established a policy in 2005 to ensure that the Strategic National Stockpile
retains a current unexpired inventory of 60 million doses of BioThrax. The US GAO reports that 4 million doses of the inventory will expire every year, requiring vaccine destruction services.
The shelf-life of BioThrax is reported to be three years, requiring non-freezing storage temperatures between 2°C to 8°C (36°F to 46°F). However, given the low risk of exposure to anthrax
, vaccination of these groups is not currently recommended by the FDA. In particular, "... Safety and effectiveness of BioThrax have not been established in pregnant women or nursing mothers, or in pediatric or geriatric populations."
Moreover, "... the safety and efficacy of BioThrax for post-exposure setting have not been established.".
The recommended therapy for post-exposure setting is a course of doxycycline
, instead of ciprofloxacin
, as announced in October 2008 by US Health and Human Services.
Ciprofloxacin is a fluoroquinolone antibiotic, which interferes with cell division (mitosis
). Adverse side-effects have been reported including chronic tendonitis, ruptured tendons, and birth defects.
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
s against the infectious disease
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
anthrax
Anthrax
Anthrax is an acute disease caused by the bacterium Bacillus anthracis. Most forms of the disease are lethal, and it affects both humans and other animals...
. Anthrax is caused by the spore
Spore
In biology, a spore is a reproductive structure that is adapted for dispersal and surviving for extended periods of time in unfavorable conditions. Spores form part of the life cycles of many bacteria, plants, algae, fungi and some protozoa. According to scientist Dr...
-forming bacterium Bacillus anthracis
Bacillus anthracis
Bacillus anthracis is the pathogen of the Anthrax acute disease. It is a Gram-positive, spore-forming, rod-shaped bacterium, with a width of 1-1.2µm and a length of 3-5µm. It can be grown in an ordinary nutrient medium under aerobic or anaerobic conditions.It is one of few bacteria known to...
, that most commonly occurs in wild and domestic mammals. Anthrax also occurs in humans when they are exposed to infected animals, hides, or tissue from infected animals, or when they are directly exposed to B. anthracis. Depending on the route of infection, anthrax disease can occur in three forms: cutaneous, inhalational, and rarely, gastrointestinal.
Licensing and product in the USA
The only FDA-licensed human anthrax vaccine' in the United StatesUnited States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, Anthrax Vaccine Adsorbed (AVA, trade name BioThrax), is produced by Emergent BioDefense Corporation, formerly known as BioPort Corporation in Lansing, Michigan
Lansing, Michigan
Lansing is the capital of the U.S. state of Michigan. It is located mostly in Ingham County, although small portions of the city extend into Eaton County. The 2010 Census places the city's population at 114,297, making it the fifth largest city in Michigan...
. The parent company of Emergent BioDefense is Emergent BioSolutions
Emergent BioSolutions
Emergent BioSolutions is a multinational biopharmaceutical company headquartered in Rockville, Maryland. Emergent develops vaccines and therapeutics targeting infectious diseases, oncology and autoimmune disorders. Founded as BioPort Corporation in 1998, the company was named Emergent...
of Rockville, Maryland. Both Emergent BioSolutions
Emergent BioSolutions
Emergent BioSolutions is a multinational biopharmaceutical company headquartered in Rockville, Maryland. Emergent develops vaccines and therapeutics targeting infectious diseases, oncology and autoimmune disorders. Founded as BioPort Corporation in 1998, the company was named Emergent...
and Porton International Group, Ltd., Porton Down
Porton Down
Porton Down is a United Kingdom government and military science park. It is situated slightly northeast of Porton near Salisbury in Wiltshire, England. To the northwest lies the MoD Boscombe Down test range facility which is operated by QinetiQ...
, UK, are controlled by Fuad El-Hibri
Fuad El-Hibri
Fuad El-Hibri is an American businessman, and CEO of Emergent BioSolutions.-Early life:Fuad El-Hibri in Hildesheim, Germany spent his childhood equally in Europe and the Middle East before coming to the USA to get an economics degree from Stanford and an MBA from Yale-Education:El-Hibri earned a...
.
The anthrax vaccine is produced from culture filtrates of an avirulent, nonencapsulated strain known as V770-NP1-R. No living organisms are present in the vaccine. In the U.S., the principal purchasers of the vaccine are the Department of Defense
United States Department of Defense
The United States Department of Defense is the U.S...
and Department of Health and Human Services. Ten million doses of the vaccine have been purchased for the U.S. Strategic National Stockpile
Strategic National Stockpile
The Strategic National Stockpile is the United States' national repository of antibiotics, vaccines, chemical antidotes, antitoxins and other critical medical equipment and supplies...
.
The anthrax vaccine was originally licensed in 1970 by the U.S. National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
(NIH) and in 1972 the U.S. Food and Drug Administration (FDA) took over responsibility for vaccine licensure and oversight. In 1997, the Clinton administration initiated the Anthrax Vaccine Immunization Program
Anthrax Vaccine Immunization Program
The Anthrax Vaccine Immunization Program , is the name of the policy set forth by the Federal government of the United States to immunize its military and specific civilian personnel with the anthrax vaccine. It began in earnest in 1997 by the Clinton administration...
, under which active U.S. service personnel were to be immunized with the vaccine. Much controversy has surrounded the program since its inception. Since vaccination was mandatory, a perception developed that the anthrax vaccine was unsafe, causing sometimes serious side effects. Mandatory vaccinations were halted due to an injunction which was put into place on October 27, 2004. The injunction cast questions about numerous substantive challenges regarding the anthrax vaccine in footnote #10, yet the procedural findings centered on FDA procedural issues, stating that additional public comment should have been sought before the FDA issued its Final Rule declaring the vaccine safe and effective in December 2003. The FDA's incomplete rulemaking from 1985 effectively rendered the anthrax vaccine program illegal. The basis was the never finalized FDA Proposed Rule. In that rulemaking the FDA published, but never finalized, a licensing rule for the anthrax vaccine in the Federal Register, which included an expert review panel's findings. Those findings included the fact that the "Anthrax vaccine efficacy against inhalation anthrax is not well documented," and that "No meaningful assessment of its value against inhalation anthrax is possible due to its low incidence," and that "The vaccine manufactured by the Michigan Department of Public Health has not been employed in a controlled field trial." On December 15, 2005, the FDA re-issued a Final Rule & Order on the license status of the anthrax vaccine.
After reviewing extensive scientific evidence, but failing to address a variety of substantive issues of safety and efficacy raised in the public comments, the FDA again determined that the vaccine is licensed for the prevention of anthrax, regardless of the route of exposure. On October 16, 2006, the Defense Department announced the reinstatement of mandatory anthrax vaccinations for more than 200,000 troops and defense contractors. Then another lawsuit was filed by the same attorneys as before, challenging the basis of the vaccine's license on scientific grounds. The vaccinations will be required for most military units and civilian contractors assigned to homeland bioterrorism defense or deployed in Iraq, Afghanistan or South Korea.
Vaccination schedule
VaccinationVaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
with Emergent BioSolutions
Emergent BioSolutions
Emergent BioSolutions is a multinational biopharmaceutical company headquartered in Rockville, Maryland. Emergent develops vaccines and therapeutics targeting infectious diseases, oncology and autoimmune disorders. Founded as BioPort Corporation in 1998, the company was named Emergent...
BioThrax AVA and BioThrax IM intramuscular injections in the deltoid is given at 0 and 4 weeks, with three vaccinations at 6, 12, and 18 months, followed by annual boosters.
As of December 2008, the new BioThrax IM for intramuscular injections in the deltoid was approved by the US FDA which changes the immunity initialization sequence from 6 to 5 shots given at 0 and 4 weeks and then at 6, 12, and 18 months, followed by annual boosters. This prolonged initialization sequence is required with annual booster shots, because the anthrax vaccine's primary ingredient, the Anthrax Protective Antigen, can impair the life-cycle of the human immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
's memory B-Cells and memory T-cells, through inducing the production of immunoglobulin G
Immunoglobulin G
Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...
(IgG) which sequesters furin
Furin
Furin is a protein that in humans is encoded by the FURIN gene. It was named furin because it was in the upstream region of an oncogene known as FES. The gene was known as FUR and therefore the protein was named furin...
.
The loss of memory B-Cells leads to declining concentrations of IgG which can sequester APA, and therefore declining tolerance to the presence of anthrax bacteria. There is the potential that other memory B-Cell populations will be adversely affected as well.
Furin is the protein activator for pro-parathyroid hormone
Parathyroid hormone
Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...
, transforming growth factor beta 1, von Willebrand factor
Von Willebrand factor
von Willebrand factor is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome...
, pro-albumin
Albumin
Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
, pro-beta-secretase
Beta-secretase
Beta-secretase 1 also known as beta-site APP cleaving enzyme 1 , memapsin-2 , and aspartyl protease 2 is an enzyme that in humans is encoded by the BACE1 gene.β-Secretase is an aspartic-acid protease important in the pathogenesis of Alzheimer's disease,...
, membrane type-1 matrix metalloproteinase
MMP1
Interstitial collagenase also known as matrix metalloproteinase-1 and fibroblast collagenase is an enzyme that in humans is encoded by the MMP1 gene.- Function :...
, gonadotropin
Gonadotropin
Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...
, and nerve growth factor
Nerve growth factor
Nerve growth factor is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons . It also functions as a signaling molecule. It is perhaps the prototypical growth factor, in that it is one of the first to be described...
. Furin is also essential to maintain peripheral immune tolerance by creating memory T-cells and suppressor T-cells.
Because IgG will cross the maternal fetoplacental blood-barrier, Furin-sequestering IgG can cause severe congenital birth defects during pregnancy.
The approved US FDA package insert for Anthrax Vaccine Adsorbed contains the following notice:
Pregnant women should not be vaccinated against anthrax unless the potential benefits of vaccination have been determined to outweigh the potential risk to the fetus. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this product, the patient should be apprised of the potential hazard to the fetus.
Contraindications
The approved US FDA] package insert for Anthrax Vaccine Adsorbed contains the following notice:* Severe allergic reaction (e.g., anaphylaxis) after a previous dose of BioThrax&trade.
* Administer with caution to patients with a possible history of latex sensitivity because the vial stopper contains dry natural rubber and may cause allergic reactions.
Adverse reactions
The approved US FDA package insert for Anthrax Vaccine Adsorbed contains the following notice:The most common (>10%) local (injection-site) adverse reactions observed in clinical studies were tenderness, pain, erythema and arm motion limitation. The most common (>5%) systemic adverse reactions were muscle aches, fatigue and headache.
Serious allergic reactions, including anaphylactic shock, have been observed during post-marketing surveillance in individuals receiving BioThrax™.
Drug interactions
The approved US FDA package insert for Anthrax Vaccine Adsorbed contains the following notice:Immunosuppressive therapies may diminish the immune response to BioThrax.
Adjuvant
The Anthrax Vaccine Adsorbed contains aluminium hydroxideAluminium hydroxide
Aluminium hydroxide, Al3, ATH, sometimes erroneously called Hydrate of alumina, is found in nature as the mineral gibbsite and its three, much more rare forms, polymorphs: bayerite, doyleite and nordstrandite. Closely related are aluminium oxide hydroxide, AlO, and aluminium oxide, Al2O3,...
as an adjuvant
Immunologic adjuvant
In immunology, an adjuvant is an agent that may stimulate the immune system and increase the response to a vaccine, without having any specific antigenic effect in itself. The word “adjuvant” comes from the Latin word adiuvare, meaning to help or aid...
. Each dose of the vaccine contains no more than 0.83 mg aluminum per 0.5 mL dose. This is near the allowed upper limit of 0.85 mg/dose. The BioPort anthrax vaccine also contains 0.0025% benzethonium chloride
Benzethonium chloride
Benzethonium chloride is a synthetic quaternary ammonium salt. This compound is an odorless white solid; soluble in water. It has surfactant, antiseptic, and anti-infective properties, and it is used as a topical antimicrobial agent in first aid antiseptics. It is also found in cosmetics and...
as a preservative, and 0.0037% formaldehyde
Formaldehyde
Formaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...
as a stabilizer.
In 2007, tests with mice of the anthrax vaccine using aluminum hydroxide adjuvant were reported as resulting in adverse neuropathy symptoms.
Controversy
The United States Centers for Disease ControlCenters for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
(CDC) reported that from 1990 to 2000, more than 1,859,000 doses of anthrax vaccine were distributed in the United States. During that decade, 1,544 adverse events
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
(.08% of total doses) were reported to the Vaccine Adverse Event Reporting System
Vaccine Adverse Event Reporting System
The Vaccine Adverse Event Reporting System is a United States program for vaccine safety, co-managed by the Centers for Disease Control and Prevention and the Food and Drug Administration . VAERS is a post-marketing safety surveillance program, collecting information about adverse events that...
(VAERS), 76 of these events (5%, 0.004% of total doses) were serious ("results in death, hospitalization, or permanent disability or is life-threatening"). Reports to VAERS are not necessarily events that have a cause and effect relationship, and the number of unreported adverse events caused by vaccines is unknown. These figures are intrinsically misleading in as much as the VAERS system is a passive system, meaning that an adverse event can only enter the system if the vaccinee or vaccinator take notice and report it. In other words, CDC cannot actively follow recipients of every dose of every vaccine to check for adverse events; its surveillance to a large extent has to rely on the vigilance and thoroughness of vaccine providers and recipients.
Although individuals have expressed health concerns after receiving anthrax vaccine, a congressionally directed study by the Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...
(part of the National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
) concluded that anthrax vaccine is as safe as other vaccines. The Academy considered more than a dozen studies using various scientific designs, and heard personally from many concerned US military service members.
Concern has been raised that the Pentagon
The Pentagon
The Pentagon is the headquarters of the United States Department of Defense, located in Arlington County, Virginia. As a symbol of the U.S. military, "the Pentagon" is often used metonymically to refer to the Department of Defense rather than the building itself.Designed by the American architect...
did not inform the United States Congress
United States Congress
The United States Congress is the bicameral legislature of the federal government of the United States, consisting of the Senate and the House of Representatives. The Congress meets in the United States Capitol in Washington, D.C....
about more than 20,000 hospitalizations involving troops who had received the anthrax vaccine, because "hospitalizations merely followed vaccinations in time, without documented proof of a cause-and-effect relationship." Independent researchers, David and Mark Geier, published "Anthrax vaccination and joint related adverse reactions in light of biological warfare scenarios" in Clinical and Experimental Rheumatology in 2002 vol. 20 page 119. They also published "Gastrointestinal adverse reactions following anthrax vaccination" in Hepatogastroenterology in 2004 vol. 51 page 762. The Geiers found a very large and statistically significant increase in joint symptoms and gastrointestinal problems following vaccination with anthrax vaccine. These authors concluded that due to the extreme reactogenicity of anthrax vaccine, its general use in the civilian population is undesirable. The safety of the U.S. anthrax vaccine continues to be an active area of study for both government and non-government personnel, but to date no data have been found that have caused the FDA to declare the vaccine anything other than safe and effective.
Controversy in Israel
Beginning in 1998 and running for 8 years, project Omer Two tested an anthrax vaccine on 716 volunteers of the Israel Defense ForcesIsrael Defense Forces
The Israel Defense Forces , commonly known in Israel by the Hebrew acronym Tzahal , are the military forces of the State of Israel. They consist of the ground forces, air force and navy. It is the sole military wing of the Israeli security forces, and has no civilian jurisdiction within Israel...
. Adverse multi-symptom illnesses were reported by a group of the volunteers. All were denied disability by the Defense Ministry. In February 2009, a petition from the disabled volunteers to disclose a report about Omer Two was filed with the Israel's High Court against the Defense Ministry, the Israel Institute for Biological Research
Israel Institute for Biological Research
Israel Institute for Biological Research is a government defense research institute specializing in biology, medicinal chemistry and environmental science, and is suspected of also developing biological and chemical weapons, as well as defenses against them. It is located in Ness Ziona, 20...
at Nes Tziona, the director, Avigdor Shafferman, and the IDF Medical Corps. Release of the information could support further action to provide disability compensation for the injured volunteers.
Development of a new vaccine
While effective in protecting against anthrax, the licensed vaccine schedule is not very efficient, involving a cumbersome six dose injection series. Typically, six injections are given over a period of 18 months in order to induce a protective immune system response. The Centers for Disease Control and PreventionCenters for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
have undertaken a clinical trial to investigate more abbreviated vaccinations schedules for AVA. In addition, in 2004 the U.S. Department of Health and Human Services contracted with Vaxgen
VaxGen
VaxGen is a biopharmaceutical company based in the San Francisco Bay Area.As of July 28, 2010, VaxGen Inc. was acquired by diaDexus, Inc., in a reverse merger transaction. VaxGen, Inc. does not have significant operations. The company seeks to enter into a strategic transaction or series of...
Inc. to supply up to 75 million doses of a recombinant
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
anthrax vaccine, for $877 million. To be acceptable to HHS, this vaccine was to be protective against anthrax in three doses or less. On December 19, 2006, HHS voided the contract, because of stability problems with the vaccine, and a failure to start a Phase 2 clinical trial on time. In May 2008, Emergent Biosolutions, the Maryland-based successor to BioPort, both controlled by former Lebanese banker Faud el Hibri, acquired rights to Vaxgen's patents and processes.
Research is being done to develop and test new anthrax vaccines. One possible new type of vaccine would be administered by a skin patch rather than by injection.
Human Genome Sciences announced in 2007 the development of a new anthrax vaccine with the trademark name of ABthrax. The vaccine sensitizes the human immune system to the presence of the Anthrax Toxin Factor. In 2008, HGS reported on testing on 400 human volunteers given ABthrax. In 2009, HGS announced that they had made first delivery of 20,000 doses of ABthrax to the United States Department of Defense.
Licensing and product in the UK
The UK anthrax vaccine, manufactured by the Health Protection AgencyHealth Protection Agency
The Health Protection Agency, or, in Welsh, Yr Asiantaeth Diogelu Iechyd is a statutory corporation. It is an independent UK organisation that was set up by the government in 2003 to protect the public from threats to their health from infectious diseases and environmental hazards...
, is similar to that made in the U.S. The active ingredient in the vaccine is a sterile filtrate of an alum precipitated anthrax antigen from the Sterne strain in a solution for injection. The other ingredients are aluminium potassium sulphate, sodium chloride and purified water. The preservative is thiomersal (0.005%). The vaccine is given by intramuscular injection and the primary course of four single injections (three injections 3 weeks apart, followed by a 6 month dose) is followed by a single booster dose given once a year.
During Gulf War I, 1990–1991, the UK military were given the UK anthrax vaccine co-commitantly with the pertussis vaccine
Pertussis vaccine
Pertussis vaccine is a vaccine used against Bordetella pertussis.It is a component of the DPT vaccine.Older versions of the vaccine involved inactivated cells. Newer versions are acellular, and are less likely to provoke a febrile state....
as an adjuvant to improve the immune response efficacy of the UK anthrax vaccine.
Licensing and Product in India
On February 12, 2009, Emergent BioSolutionsEmergent BioSolutions
Emergent BioSolutions is a multinational biopharmaceutical company headquartered in Rockville, Maryland. Emergent develops vaccines and therapeutics targeting infectious diseases, oncology and autoimmune disorders. Founded as BioPort Corporation in 1998, the company was named Emergent...
announced that the Drugs Controller General of India (DGCI) had approved licensing of BioThrax AVA for distribution by Biological E. of Hyderabad.
Bioterrorism preparedness
Demographic groups, ages 18 to 65, are being considered for preexposure vaccination, for bioterrorismBioterrorism
Bioterrorism is terrorism involving the intentional release or dissemination of biological agents. These agents are bacteria, viruses, or toxins, and may be in a naturally occurring or a human-modified form. For the use of this method in warfare, see biological warfare.-Definition:According to the...
preparedness, included emergency first responders such as police and firefighters, federal responders, medical practitioners, and private citizens. To that end, under the George W. Bush administration, the US established a policy in 2005 to ensure that the Strategic National Stockpile
Strategic National Stockpile
The Strategic National Stockpile is the United States' national repository of antibiotics, vaccines, chemical antidotes, antitoxins and other critical medical equipment and supplies...
retains a current unexpired inventory of 60 million doses of BioThrax. The US GAO reports that 4 million doses of the inventory will expire every year, requiring vaccine destruction services.
The shelf-life of BioThrax is reported to be three years, requiring non-freezing storage temperatures between 2°C to 8°C (36°F to 46°F). However, given the low risk of exposure to anthrax
Anthrax
Anthrax is an acute disease caused by the bacterium Bacillus anthracis. Most forms of the disease are lethal, and it affects both humans and other animals...
, vaccination of these groups is not currently recommended by the FDA. In particular, "... Safety and effectiveness of BioThrax have not been established in pregnant women or nursing mothers, or in pediatric or geriatric populations."
Moreover, "... the safety and efficacy of BioThrax for post-exposure setting have not been established.".
The recommended therapy for post-exposure setting is a course of doxycycline
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
, instead of ciprofloxacin
Ciprofloxacin
Ciprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class.It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of...
, as announced in October 2008 by US Health and Human Services.
Ciprofloxacin is a fluoroquinolone antibiotic, which interferes with cell division (mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
). Adverse side-effects have been reported including chronic tendonitis, ruptured tendons, and birth defects.
External links
- U.S. anthrax vaccine package insert
- Gulf War Syndrome Fact or Fiction.
- Anthrax.osd.mil - 'AVIP: Anthrax Vaccine Immunization ProgramAnthrax Vaccine Immunization ProgramThe Anthrax Vaccine Immunization Program , is the name of the policy set forth by the Federal government of the United States to immunize its military and specific civilian personnel with the anthrax vaccine. It began in earnest in 1997 by the Clinton administration...
a matter of health, a matter of trust, a matter of national security' - AnthraxVaccine.org- An anti-vaccine web site containing 'Information on anthrax, anthrax vaccine, biological warfareBiological warfareBiological warfare is the use of biological toxins or infectious agents such as bacteria, viruses, and fungi with intent to kill or incapacitate humans, animals or plants as an act of war...
and related studies of anthrax vaccinations' - EmergentBioSolutions.com - Emergent BioSolutions Corporation home page, parent company of BioPort.
- NAP.edu - 'The Anthrax Vaccine: Is It Safe? Does It Work?', Lois M. Joellenbeck, Lee L. Zwanziger, Jane S. Durch, Brian L. Strom (editors), Committee to Assess the Safety and Efficacy of the Anthrax Vaccine, Medical Follow-Up Agency
- NCTimes.com - 'Troop anthrax shots in question', Darrin Mortenson, North County TimesNorth County TimesThe North County Times is a local newspaper in north San Diego County, California owned by Lee Enterprises. It is headquartered in Escondido. The current publisher is Peter York....
, (December 29, 2003) - Salon.com - 'A shot in the dark: The U.S. military requires troops to take controversial anthrax shots and court-martialCourt-martialA court-martial is a military court. A court-martial is empowered to determine the guilt of members of the armed forces subject to military law, and, if the defendant is found guilty, to decide upon punishment.Most militaries maintain a court-martial system to try cases in which a breach of...
s them if they refuse. But critics say the vaccine is too dangerous—and with Saddam'sSaddam HusseinSaddam Hussein Abd al-Majid al-Tikriti was the fifth President of Iraq, serving in this capacity from 16 July 1979 until 9 April 2003...
bioweapons nowhere to be found, needless', Eric Boehlert, Salon.comSalon.comSalon.com, part of Salon Media Group , often just called Salon, is an online liberal magazine, with content updated each weekday. Salon was founded by David Talbot and launched on November 20, 1995. It was the internet's first online-only commercial publication. The magazine focuses on U.S...
, (December 10, 2003) - TheOlympian.com - '20,000 who got anthrax shot were hospitalized', Bob Evans, Daily Press (December 10, 2005)
- NY Dept. of Health information sheet. In pdf format.