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Showing papers on "Anthrax vaccines published in 2000"


Journal ArticleDOI
TL;DR: Results suggest that some B. anthracisspore-associated antigen(s) may contribute in a significant manner to protective immunity and appear to be more efficacious than the vegetative cell vaccine.
Abstract: The etiological agent of anthrax disease in animals and humans is the spore-forming bacterium Bacillus anthracis. The major factors of virulence of B. anthracis are located on two plasmids, pXO1 and pXO2. pXO2 encodes a poly-d-glutamic acid capsule (19, 41), while pXO1 encodes two binary exotoxins, the lethal toxin (LT) and the edema toxin (ET) (43, 46, 61). These two toxins are composed of three different proteins: protective antigen (PA), edema factor (EF), and lethal factor (LF) (for a review, see reference 36). PA is the common receptor binding domain of the toxins and can interact with the two different effector domains, EF and LF, to mediate their entry into target cells (14). EF is a calmodulin-dependent adenylate cyclase (37) responsible for the edema seen at the site of infection in experimental animals (17). The LF is a metalloprotease (34) recently shown to cleave the amino termini of the mitogen-activated protein kinase kinases 1 and 2, which results in their inactivation (13). It remains to be determined whether these are the main physiological substrates for the LT activity in vivo (5, 22). Two types of anthrax vaccines are licensed for use in humans: the spores of the toxigenic, nonencapsulated B. anthracis STI-1 strain (55) and the cell-free PA-based vaccines consisting of aluminum hydroxide-adsorbed supernatant material from cultures of the toxigenic, nonencapsulated B. anthracis strain V770-NPI-R (49) or alum-precipitated culture filtrate from the Sterne strain (6). The use of the live attenuated STI-1 occasionally results in general and local adverse responses, observed both after primary application and revaccination, and the frequency of responses increases with the number of vaccinations (58). Furthermore, it was reported that the STI-1 vaccine has a relatively low immunogenicity (reviewed by Stepanov et al. in reference 58). To increase the immunogenicity, a combined vaccine of live STI-1 supplemented with cell-free PA formulation was evaluated and proposed for veterinary use (1). While the cell-free PA-based vaccines appear to be safer, they require numerous boosters (8) and were shown to have reduced ability to protect laboratory animals against certain virulent strains of B. anthracis (39, 60). In addition, these vaccines contain variable amounts of PA, as well as undefined quantities of LF and EF, adsorbed to aluminum hydroxide (4, 21, 49, 59). It appears, therefore, that there is a need for a safe and more efficient vaccine which could generate stable and prolonged immunity in humans (59). These conclusions led to the evaluation of various adjuvants with purified PA (2, 16, 29, 59) and to the creation of two types of live vaccines: vaccines based on nonvirulent B. anthracis (pXO1+) mutated strains (31, 47) and vaccines expressing PA from a cloned pagA gene using heterologous hosts such as the vaccinia virus, Bacillus subtilis, Salmonella typhimurium (10, 27, 28, 30, 31, 64), or a nontoxinogenic strain of B. anthracis (4). These pioneering studies suggest that recombinant B. anthracis live vaccines may have potential as a future anthrax vaccine. We report here the construction of several recombinant, nonencapsulated, and nontoxinogenic B. anthracis spore-forming strains expressing different levels of PA. We demonstrate that one of these strains, containing the pagA gene under a potent heterologous constitutive promoter, can be safely used to provide efficacious long-lasting immunity in experimental animals following a single immunization dose.

154 citations


Journal ArticleDOI
TL;DR: Despite two decades of elegant science aimed at formulating alternative vaccines to overcome all the problems of efficacy, safety and supply, such an alternative is at least five years away, and the current status is that the authors must live with the old vaccines or not vaccinate.
Abstract: Anthrax vaccination has become a ‘hot’ topic. On the one hand, fears that Iraq holds secret caches of anthrax-based weaponry, that other countries may be developing or may have developed similar devices, or that hard-line groups may make their own anthrax-based devices for bioterrorist attacks have focused official attention on the need for means of protection, principally, though, for the military. On the other hand, the unsolved issues of the Gulf War illnesses have left elements of doubt in the minds of some as to the possible role of anthrax (among other) vaccines in this syndrome, and have drawn attention to the shortage of pre-clinical, clinical, pharmacological and safety data on the existing UK and US anthrax vaccines. In the middle are those hotly debating the US and Canadian policies of mandatory anthrax immunization for military personnel or, in the case of the UK policy of voluntary immunization, simply voting with their feet. Compounding matters have been the publicized failures of the US vaccine production facility and the less publicized UK problems of supply. Meanwhile, those in genuine at-risk occupations are left unsure whether, if they can get the vaccine at all, they really want it. Despite two decades of elegant science aimed at formulating alternative vaccines to overcome all the problems of efficacy, safety and supply, such an alternative is at least five years away, and the current status is that we must live with the old vaccines or not vaccinate.

78 citations


Journal ArticleDOI
29 Apr 2000-BMJ
TL;DR: The Pentagon has embarked on a massive effort to produce this vaccine and to inoculate all US troops on active duty and this programme is now under sharp attack in Congress for possible adverse …
Abstract: EDITOR—Rosen makes several factual misstatements in his editorial on bioterrorism.1 For example, the vaccine for anthrax has been shown to be effective only for the cutaneous form of anthrax and not for the inhalation form used in weapons.2 He states that anthrax vaccine is not being produced, but the Pentagon has embarked on a massive effort to produce this vaccine and to inoculate all US troops on active duty. This programme is now under sharp attack in Congress for possible adverse …

7 citations



01 Jan 2000
TL;DR: The strategy of using multiple vaccines to protect against biological warfare agents must be re-evaluated in the context of integrated warfare and the potential simultaneous exposure of forces to chemical, biological and radiological agents along with conventional warfare environmental exposures.
Abstract: Although all U.S. Armed Forces personnel have been ordered to receive the anthrax vaccine, questions remain concerning its efficacy and safety and its intended use to counter a biological weapons threat. Since published data on the anthrax vaccine are scarce, it is difficult if not impossible to evaluate claims on its effectiveness and safety. In addition, questions concerning its safety have been raised, based on reports that associate the anthrax vaccine with high frequencies of adverse reactions and chronic illnesses. The chronic signs and symptoms associated with anthrax vaccination are similar to those found in Gulf War Illness patients, suggesting that at least some of the chronic illnesses suffered by veterans of the 1991 Gulf War may have been caused by vaccines. Commercial vaccines are often contaminated with microorganisms, such as Mycoplasma species, and this type of microbe has been found in the blood of a sizable subset of Gulf War Illness patients along with antibodies against an unapproved vaccine adjuvant. With concerns about safety and efficacy of the military's vaccines, the strategy of using multiple vaccines to protect against biological warfare agents must be re-evaluated in the context of integrated warfare and the potential simultaneous exposure of forces to chemical, biological and radiological agents along with conventional warfare environmental (smoke, chemicals, etc.) exposures. Introduction—Anthrax Biological Warfare To counter an increasing threat that anthrax spores could be used as a biological warfare (BW) agent all U.S. Armed Forces personnel, including reserve and National Guard members, were ordered to receive anthrax vaccine. This decision has resulted in disciplinary hearings among U.S. Armed Forces personnel who have refused, based on safety considerations, the anthrax vaccine. 1

6 citations


Journal ArticleDOI
21 Jul 2000-Science
TL;DR: For example, the anthrax bacterium, once the deadly scourge of goat-hair workers, has become the bane of the U.S. defense establishment and without infecting a single soldier, it has created a logistical headache for the Pentagon, as military contractors have fallen far short of supplying a vaccine that will protect all troops and be acceptable to health authorities as discussed by the authors.
Abstract: Anthrax bacterium, once the deadly scourge of goat-hair workers, has become the bane of the U.S. defense establishment. Without infecting a single soldier, it has created a logistical headache for the Pentagon, as military contractors have fallen far short of supplying a vaccine that will protect all troops and be acceptable to health authorities. Last week military officials were forced to beat a hasty retreat in their current efforts, raising the hackles of legislators who already had serious doubts about the program.

5 citations