Anthrax vaccine adsorbed
Vaccine description | |
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Target | Bacillus anthracis |
Vaccine type | Subunit |
Clinical data | |
Trade names | Biothrax, Cyfendus |
Other names | rPA102 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a607013 |
License data | |
intramuscular | |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
DrugBank | |
ChemSpider |
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UNII | |
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Anthrax vaccine adsorbed, sold under the brand name Biothrax among others, is a
Anthrax vaccine adsorbed originated in studies done in the 1950s and was first licensed for use in humans in 1970. In the US, the principal purchasers of the vaccine are the
Medical uses
Anthrax vaccine adsorbed (Biothrax) is
Anthrax vaccine adsorbed, adjuvanted (Cyfendus) is indicated for post-exposure prophylaxis of disease following suspected or confirmed exposure to Bacillus anthracis in people aged 18 through 65 years of age when administered in conjunction with recommended antibacterial drugs.[5]
Description
Anthrax vaccine adsorbed was developed by Emergent Biodefense Operations.
Antigen
Anthrax vaccine adsorbed is classified as a subunit vaccine that is cell-free and containing no whole or live anthrax bacteria.
Adjuvant
Anthrax vaccine adsorbed contains aluminium hydroxide (alhydrogel) to adsorb PA as well as to serve as an adjuvant (immune enhancer).[7] As such it is believed to stimulate humoral, but not cell-mediated, immunity.[12] 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.[13]) It also contains 0.0025% benzethonium chloride as a preservative and 0.0037% formaldehyde as a stabilizer.[7] The mechanism of action of the adjuvant is not entirely understood.
Potency/immunogenicity
Vaccination of humans with anthrax vaccine adsorbed induces an immune response to PA. More than 1/3 of subjects develop detectable anti-PA IgG after a single inoculation; 95% do so after a 2nd injection; and 100% after 3 doses. The peak IgG response occurs after the 4th (6 month) dose. The potency of anthrax vaccine adsorbed vaccine lots is routinely determined both by the survival rates of parenterally challenged
History
Initial research and development (1954–1970)
The
Licensure and limited occupational use (1970–1991)
In 1970, anthrax vaccine adsorbed was first licensed by the USPHS for protection against
Only several thousand people had ever received the vaccine up to 1991 when — coincident with
Initial use in US military (1991–1997)
Use of anthrax vaccine adsorbed expanded dramatically in 1991, when the US military, concerned that Iraq possessed anthrax bioweapons, administered it to some 150,000 service members deployed for the Gulf War. Hussein never deployed his bio-weapons, but subsequent confirmation of an
Meanwhile, MBPI fell afoul of FDA inspectors and reviewers when it failed inspections (1993, 1997) and received warning letters (1995) and Notices of Intention to Revoke (1997) from the agency. At issue were a failure to validate the anthrax vaccine adsorbed manufacturing process to the FDA's satisfaction and various quality control failures, including reuse of expired vaccine, inadequate testing procedures, and use of lots that had failed testing. All of these developments vexed the Army, not only in its efforts to obtain sufficient vaccine for the troops, but in its desire to have anthrax vaccine adsorbed validated and fully licensed for prevention of inhalational anthrax, which is the expected weaponized form of the disease (as opposed to the cutaneous form for which the vaccine had been licensed in 1970). In 1995, the Army contracted with the Science Applications International Corporation (SAIC) to develop a plan to obtain FDA approval for a license amendment for anthrax vaccine adsorbed in order to add inhalational anthrax exposure to the product license thus enabling the manufacturer to list on the product license that the vaccine was effective against that form of the disease. The following year, MBPI submitted an "IND application" to modify the product's license to add an indication for inhalation anthrax, thus formally establishing anthrax vaccine adsorbed as an "experimental" vaccine when used to prevent anthrax in the inhalational form.
In 1996, the US Department of Defense (DoD) sought and received permission from the FDA to begin vaccinations of all military personnel without obtaining a new licensed indication for anthrax vaccine adsorbed. It announced a plan the following year for the mandatory vaccination of all US service members. Under the plan all military personnel, including new recruits, would begin receiving what was then a six-shot series of inoculations in the following fashion: Phase 1: Forces assigned now, or soon rotating, to high threat areas in Southwest Asia and Korea; Phase 2: Early deploying forces into high threat areas; Phase 3: Remainder of the force and new recruits; and Phase 4: Continuation of the program with annual booster shots.
The AVIP and initial mandatory military use (1997–2000)
There were no published studies of anthrax vaccine adsorbed's safety in humans
Adverse events following anthrax vaccine adsorbed administration were assessed in several studies conducted by the DoD in the context of the routine anthrax vaccination program. Between 1998 and 2000, at
By 2000, some 425,976 US service members had received 1,620,793 doses of anthrax vaccine adsorbed.
The IOM review (2000–2004)
In October 2000, a committee of the
In the months after the
BioPort changed its name to Emergent BioSolutions in 2004.
Injunctions and FDA re-reviews (2004–2006)
Despite the positive IOM assessment, mandatory vaccinations of military personnel were halted due to an injunction which was put into place on 27 October 2004. The injunction cast questions about numerous substantive challenges regarding the anthrax vaccine in footnote #10,[21] 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 on 30 December 2003.[22] 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."[23]
On 15 December 2005, the FDA re-issued a Final Rule & Order on the license status of the anthrax vaccine.
Reinstatement of the AVIP (2006–2016)
On 16 October 2006, the DoD announced the reinstatement of mandatory anthrax vaccinations for more than 200,000 troops and defense contractors. (Another lawsuit was filed by the same attorneys as before, challenging the basis of the vaccine's license on scientific grounds.) The reinstated policy required vaccinations for most military units and civilian contractors assigned to homeland bioterrorism defense or deployed in Iraq, Afghanistan or South Korea.[25] A modification of previous policy allowed military personnel no longer deployed to higher threat areas to receive follow up doses and booster shots on a voluntary basis. As of June 2008, over 8 million doses of anthrax vaccine adsorbed had been administered to over 2 million US military personnel as part of the AVIP.
In December 2008, the FDA approved Biothrax for intramuscular injections thus reducing the immunization schedule from a total of 6 shots to 5 shots (see below).
In February 2009, Emergent BioSolutions announced that the
In 2011, Biothrax was approved for sale in Singapore by the Singapore Health Sciences Authority.[27]
Building 55 approval (2016)
The FDA approved the company's license (officially called a supplemental
The US federal government has a goal to stockpile 75 million doses of anthrax vaccines. The new facility and its capacity will help Emergent meet the government's security needs.[28]
Emergent worked with the
Administration
Vaccination schedule
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.[citation needed]
Furin is the protein activator for pro-
Based on a retrospective cohort study of female military members inoculated during pregnancy, there may be a small risk of birth defect for inoculation during first trimester. However, the difference between the vaccinated and unvaccinated control groups was not large enough to be conclusive.[31]
The approved US FDA package insert for Biothrax 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.[32]
Contraindications
The approved US FDA package insert for Biothrax contains the following notice:
- Severe allergic reaction (e.g., anaphylaxis) after a previous dose of Biothrax.
- 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.[32]
Adverse reactions
There have been no long-term sequelae of the known adverse events (local or systemic reactions) and no pattern of frequently reported serious adverse events for anthrax vaccine adsorbed.[18]
The approved 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,
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.[32]
Post-exposure vaccination
Some studies show that use of antibiotics effective against anthrax plus administration of anthrax vaccine adsorbed is the most beneficial approach for purposes of
Society and culture
Controversy
In the United States
Although many individuals have expressed health concerns after receiving anthrax vaccine, a congressionally directed study by the
Development of a replacement vaccine
While effective in protecting against anthrax, the licensed vaccine schedule is not very efficient, involving a cumbersome five (previously six) dose injection series. Typically, five injections are given over a period of 18 months in order to induce a protective immune system response. In addition, in 2004 the US Department of Health and Human Services contracted with
In October 2012, the US
Research is being continuously done to develop and test new improved candidate anthrax vaccines.[36][37][38] The primary immunogen of acellular existing vaccines, i.e., Protective Antigen (PA), is highly thermolabile due to inherent structural and chemical instability.[39][40][41][42] Various endeavors are underway to thermostabilize PA molecule by solvent engineering and genetic engineering approaches to generate a thermostable anthrax vaccine formulation without compromising on the immunogenicity and its protective potential.[38] The generation of a thermostable anthrax vaccine would minimize the current cold chain requirement for its storage and transport. Anthrax vaccines which would be amenable to other modes of administration such as oral, nasal, skin patch etc., are also being experimented.
Human Genome Sciences announced in 2007, the development of a new anthrax neutralizing monoclonal antibody 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.[43] Currently three anthrax antitoxin antibodies, namely, Anthrax immune globulin intravenous or 'AIGIV' (polyclonal), 'Obiltoxaximab' or 'ANTHIM' (monoclonal), and 'Raxibacumab' or 'ABthrax' (monoclonal) are approved for the treatment of inhalation anthrax.[44]
References
- ^ "Summary Basis of Decision (SBD) for Biothrax". Health Canada. 23 October 2014. Retrieved 29 May 2022.
- ^ "Drug and medical device highlights 2018: Helping you maintain and improve your health". Health Canada. 14 October 2020. Retrieved 17 April 2024.
- ^ a b c "Biothrax". U.S. Food and Drug Administration. 6 July 2023. Retrieved 25 August 2023. This article incorporates text from this source, which is in the public domain.
- ^ a b c d "Biothrax- bacillus anthracis injection, suspension". DailyMed. 15 November 2015. Retrieved 27 August 2023.
- ^ a b c "Cyfendus". U.S. Food and Drug Administration. 19 July 2023. Retrieved 25 August 2023. This article incorporates text from this source, which is in the public domain.
- ^ https://www.fda.gov/media/170445/download
- ^ a b c Biothrax Package Insert
- PMID 13972634.
- ^ Leppla SH, Klimpel KR, Singh Y, et al (June 1996), "Interaction of anthrax toxin with mammalian cells", Salisbury Medical Bulletin, Special Supplement #87, pg 91.
- PMID 10198799. Archived from the originalon 9 January 2013. Retrieved 31 October 2012.
- PMID 1771966.
- PMID 3148815.
- PMID 12184360.
- PMID 18017912.
- ^ Brachman PS and Friedlander AM (1994), "Anthrax", In: Plotkin SA and Mortimer EA (eds): Vaccines, 2nd ed.; Philadelphia, WB Saunders, pg 729.
- ^ 21 CFR Section 620.20.
- ^ Brachman (1994), Op. cit., pg 729.
- ^ PMID 10817479.
- ^ S2CID 78028756.
- W.W. Norton & Co., pp 13-14.
- ^ "John Doe #1 v. Donald H. Rumsfeld, et al" (PDF). Military Vaccine (MILVAX) Agency. 27 October 2004. Archived from the original (PDF) on 25 August 2009. Retrieved 6 May 2009.
- ^ Federal Register, 5 January 2006, vol 69: pp 255-67.
- ^ "50 FR 51002 published on Dec. 13, 1985" (PDF). Archived from the original (PDF) on 3 March 2012. Retrieved 29 October 2012.
- ^ FDA Final Order. Archived 2 November 2012 at the Wayback Machine Issued 15 December 2005.
- ^ Mandatory Vaccine Article - 'Mandatory Anthrax Shots to Return', Christopher Lee, Washington Post (17 October 2006)
- ^ "Emergent BioSolutions Announces That Biothrax (Anthrax Vaccine Adsorbed) Receives Market Authorization in India" (Press release). 12 February 2009.
- ^ Clabaugh J (24 June 2011). "Emergent gets entry to Singapore". Washington Business Journal. Retrieved 22 July 2011.
- ^ a b "FDA approves sBLA for Biothrax manufacture at Emergent BioSolutions' Building 55". Homeland Preparedness News. 16 August 2016. Retrieved 23 August 2016.
- ^ "Emergent BioSolutions Receives FDA Approval for Large-Scale Manufacturing of Biothrax in Building 55". Yahoo Finance. 15 August 2016. Retrieved 23 August 2016.
- PMID 18701887.
- PMID 18599489.
- ^ a b c d e US FDA, Center for Biologics Evaluation and Research CBER, Product Approval Information for Anthrax Vaccine Adsorbed (December 2008)
- ^ Vaxgen anthrax vaccine contract information. Archived 31 December 2006 at the Wayback Machine
- ^ Heavey S (20 December 2006). "U.S. cancels VaxGen anthrax vaccine contract". The Washington Post. Retrieved 25 January 2020.
- ^ "VaxGen sells anthrax vaccine candidate to Emergent BioSolutions". Forbes Magazine. 2008. Archived from the original on 9 February 2009.
- PMID 15467819.
- ISBN 978-1-4557-0090-5.
- ^ S2CID 220877509.
- PMID 15336568.
- S2CID 21178350.
- PMID 12207879.
- PMID 23242822.
- ^ BioWatch: HGS shipping anthrax treatment in $150M deal Archived 22 May 2011 at the Wayback Machine Gazette.Net - Maryland Community Newspapers Online
- PMID 31834290.
Further reading
- Donegan S, Bellamy R, Gamble CL (April 2009). "Vaccines for preventing anthrax". The Cochrane Database of Systematic Reviews. 2009 (2): CD006403. PMID 19370633.
- Borio LL (July 2005). "The Second Generation Anthrax Vaccine Candidate: rPA102". Clinicians' Biosecurity News. Archived from the original on 26 January 2020. Retrieved 26 January 2020.
External links
- "Anthrax Vaccine Information Statement". U.S. Centers for Disease Control and Prevention (CDC). 8 January 2020.
- Anthrax Vaccines at the U.S. National Library of Medicine Medical Subject Headings (MeSH)