Showing papers on "Anthrax vaccines published in 2002"

Anthrax as a biological weapon, 2002: updated recommendations for management.

Abstract: ObjectiveTo review and update consensus-based recommendations for medical and public health professionals following a Bacillus anthracis attack against a civilian population.ParticipantsThe working group included 23 experts from academic medical centers, research organizations, and governmental, military, public health, and emergency management institutions and agencies.EvidenceMEDLINE databases were searched from January 1966 to January 2002, using the Medical Subject Headings anthrax, Bacillus anthracis, biological weapon, biological terrorism, biological warfare, and biowarfare. Reference review identified work published before 1966. Participants identified unpublished sources.Consensus ProcessThe first draft synthesized the gathered information. Written comments were incorporated into subsequent drafts. The final statement incorporated all relevant evidence from the search along with consensus recommendations.ConclusionsSpecific recommendations include diagnosis of anthrax infection, indications for vaccination, therapy, postexposure prophylaxis, decontamination of the environment, and suggested research. This revised consensus statement presents new information based on the analysis of the anthrax attacks of 2001, including developments in the investigation of the anthrax attacks of 2001; important symptoms, signs, and laboratory studies; new diagnostic clues that may help future recognition of this disease; current anthrax vaccine information; updated antibiotic therapeutic considerations; and judgments about environmental surveillance and decontamination.

Anthrax Spores Make an Essential Contribution to Vaccine Efficacy

Abstract: Anthrax is caused by Bacillus anthracis, a gram-positive spore-forming bacterium. Septicemia and toxemia rapidly lead to death in infected mammal hosts. Currently used acellular vaccines against anthrax consist of protective antigen (PA), one of the anthrax toxin components. However, in experimental animals such vaccines are less protective than live attenuated strains. Here we demonstrate that the addition of formaldehyde-inactivated spores (FIS) of B. anthracis to PA elicits total protection against challenge with virulent B. anthracis strains in mice and guinea pigs. The toxin-neutralizing activities of sera from mice immunized with PA alone or PA plus FIS were similar, suggesting that the protection conferred by PA plus FIS was not only a consequence of the humoral response to PA. A PA-deficient challenge strain was constructed, and its virulence was due solely to its multiplication. Immunization with FIS alone was sufficient to protect mice partially, and guinea pigs totally, against infection with this strain. This suggests that spore antigens contribute to protection. Guinea pigs and mice had very different susceptibilities to infection with the nontoxigenic strain, highlighting the importance of verifying the pertinence of animal models for evaluating anthrax vaccines.

The Anthrax Vaccine. Is It Safe? Does It Work?

Abstract: The vaccine used to protect humans against the anthrax disease, called Anthrax Vaccine Adsorbed (AVA), was licensed in 1970. It was initially used to protect people who might be exposed to anthrax where they worked, such as veterinarians and textile plant workers who process animal hair. When the U. S. military began to administer the vaccine, then extended a plan for the mandatory vaccination of all U. S. service members, some raised concerns about the safety and efficacy of AVA and the manufacture of the vaccine. In response to these and other concerns, Congress directed the Department of Defense to support an independent examination of AVA. The Anthrax Vaccine: Is It Safe? Does It Work? reports the studya (TM)s conclusion that the vaccine is acceptably safe and effective in protecting humans against anthrax. The book also includes a description of advances needed in main areas: improving the way the vaccine is now used, expanding surveillance efforts to detect side effects from its use, and developing a better vaccine.

Development of an improved vaccine for anthrax

Abstract: Bacillus anthracis are aerobic or facultatively anaerobic Gram-positive, nonmotile rods measuring 1.0 μm wide by 3.0–5.0 μm long. Under adverse conditions, B. anthracis form highly resistant endospores (Figure ​(Figure1).1). These are found in soil at sites where infected animals previously died. Interest in the pathogenesis, immunity, and vaccine development for anthrax was heightened by the deliberate contamination of mail with B. anthracis spores soon after the September 11 attacks. At that time, the only US-licensed human vaccine (anthrax vaccine adsorbed, or AVA) was not available because the manufacturer, BioPort Corp., had not received FDA certification of its new manufacturing process. Figure 1 A spore (left) and vegetative cells and a chain of vegetative rod cells of B. anthracis. Electron micrograph courtesy of the Centers for Disease Control and Prevention. Although Pasteur had already demonstrated protection of sheep by injection of heat-attenuated B. anthracis cultures in 1881, our current knowledge of immunity to anthrax in humans remains limited. Widespread vaccination of domesticated animals with attenuated strains such as the Sterne strain began in the 1930s and has virtually abolished anthrax in industrialized countries. In the US, the licensed human vaccine (AVA, newly renamed BioThrax) is an aluminum hydroxide–adsorbed, formalin-treated culture supernatant of a toxigenic, noncapsulated, nonproteolytic B. anthracis strain, V770-NP1-R, derived from the Sterne strain (1). AVA was developed in the early 1950s, when purified components of B. anthracis were not available. Its only demonstrable protective component is the protective antigen (PA) protein (2). A similar culture supernatant–derived human vaccine is produced in the United Kingdom. Data from a 1950s trial of wool-sorters immunized with a vaccine similar to AVA, coupled with long experience with AVA and the United Kingdom vaccine, have shown that a critical level of serum antibodies to the B. anthracis PA confers immunity to anthrax (3, 4). As early as 1959, a British Ministry of Labour report noted that, following the introduction of regular immunization the previous year, the staff of the Government Wool Disinfection Station in Liverpool were free of the disease “despite the high risk to which they are exposed” (5). AVA also protects laboratory animals and cattle from both cutaneous and inhalational challenge with B. anthracis (1, 6, 7). Although safe and efficacious (8), AVA has limitations that justify the widespread interest in developing improved vaccines consisting solely of well-characterized components. First, standardization of AVA is based on the manufacturing process and a potency assay involving protection of guinea pigs challenged intracutaneously with B. anthracis spores (7, 9). PA is not measured in the vaccine, and there is no standardized assay of PA antibodies in animals or humans vaccinated with AVA. These factors probably explain why it has been difficult to maintain consistency of AVA. Second, this vaccine contains other cellular elements that probably contribute to the relatively high rate of local and systemic reactions (8). Finally, the schedule of AVA administration (subcutaneous injections at 0, 2, and 4 weeks and 6, 12, and 18 months with subsequent yearly boosters) is probably not optimal. This schedule, introduced in the 1950s, was designed for rapid induction of immunity (10), but it was recently shown that increasing the interval between the first two injections enhances the level of AVA-induced antibodies to PA (11). Moreover, there is no experimental support for including the injections given at 6, 12, and 18 months.

A recombinant carboxy-terminal domain of the protective antigen of Bacillus anthracis protects mice against anthrax infection.

Abstract: The immunogenicity and protective efficacy of overlapping regions of the protective antigen (PA) polypeptide, cloned and expressed as glutathione S-transferase fusion proteins, have been assessed. Results show that protection can be attributed to individual domains and imply that it is domain 4 which contains the dominant protective epitopes of PA.

Efficiency of Protection of Guinea Pigs against Infection with Bacillus anthracis Spores by Passive Immunization

Abstract: The efficacy of passive immunization as a postexposure prophylactic measure for treatment of guinea pigs intranasally infected with Bacillus anthracis spores was evaluated. Antisera directed either against the lethal toxin components (PA or LF) or against a toxinogenic strain (Sterne) were used for this evaluation. All antisera exhibited high enzyme-linked immunosorbent assay titers against the corresponding antigens, high titers of neutralization of cytotoxicity activity in an in vitro mouse macrophages cell line (J774A.1), as well as in vivo neutralization of toxicity when administered either directly to Fisher rats prior to challenge with the lethal toxin or after incubation with the lethal toxin. In these tests, anti-LF antiserum exhibited the highest neutralization efficiency, followed by anti-Sterne and anti-PA. The time dependence and antibody dose necessary for conferring postexposure protection by the various antibodies of guinea pigs infected with 25 50% lethal doses of Vollum spores was examined. Rabbit anti-PA serum was found to be the most effective. Intraperitoneal injections of anti-PA serum given 24 h postinfection protected 90% of the infected animals, whereas anti-Sterne and anti-LF were less effective. These results further emphasizes the importance of anti-PA antibodies in conferring protection against B. anthracis infection and demonstrated the ability of such antibodies to be effectively applied as an efficient postexposure treatment against anthrax disease.

Mucosal or parenteral administration of microsphere-associated Bacillus anthracis protective antigen protects against anthrax infection in mice.

Abstract: Existing licensed anthrax vaccines are administered parenterally and require multiple doses to induce protective immunity. This requires trained personnel and is not the optimum route for stimulating a mucosal immune response. Microencapsulation of vaccine antigens offers a number of advantages over traditional vaccine formulations, including stability without refrigeration and the potential for utilizing less invasive routes of administration. Recombinant protective antigen (rPA), the dominant antigen for protection against anthrax infection, was encapsulated in poly-l-lactide 100-kDa microspheres. Alternatively, rPA was loosely attached to the surfaces of microspheres by lyophilization. All of the microspheric formulations were administered to A/J mice with a two-dose schedule by either the intramuscular route, the intranasal route, or a combination of these two routes, and immunogenicity and protective efficacy were assessed. An intramuscular priming immunization followed by either an intramuscular or intranasal boost gave optimum anti-rPA immunoglobulin G titers. Despite differences in rPA-specific antibody titers, all immunized mice survived an injected challenge consisting of 103 median lethal doses of Bacillus anthracis STI spores. Immunization with microencapsulated and microsphere-associated formulations of rPA also protected against aerosol challenge with 30 median lethal doses of STI spores. These results show that rPA can be encapsulated and surface bound to polymeric microspheres without impairing its immunogenicity and also that mucosal or parenteral administration of microspheric formulations of rPA efficiently protects mice against both injected and aerosol challenges with B. anthracis spores. Microspheric formulations of rPA could represent the next generation of anthrax vaccines, which could require fewer doses because they are more potent, are less reactogenic than currently available human anthrax vaccines, and could be self-administered without injection.

Relationship between prepregnancy anthrax vaccination and pregnancy and birth outcomes among US Army women

Abstract: ContextSubstantial concern surrounds the potential health effects of the anthrax vaccine, particularly the potential adverse effects on reproductive processes.ObjectiveTo determine whether receipt of anthrax vaccination by reproductive-aged women has an effect on pregnancy rates.Design, Setting, and PatientsCohort study, based on information from a computer database, of women aged 17 to 44 years who were stationed at Fort Stewart, Ga, or Hunter Army Airfield, Ga, from January 1999 through March 2000.Main Outcome MeasuresPregnancy and birth rates and adverse birth outcomes.ResultsOf a total of 4092 women, 3136 received at least 1 dose of the anthrax vaccine. There was a total of 513 pregnancies, with 385 following at least 1 dose of anthrax vaccine. The pregnancy rate ratio (before and after adjustment for marital status, race, and age) comparing vaccinated with unvaccinated women was 0.94 (95% confidence interval [CI], 0.8-1.2; P = .60). There were 353 live births and 25 pregnancies lost to follow-up. The birth odds ratio after anthrax vaccination (before and after adjustment for marital status and age) was 0.9 (95% CI, 0.5-1.4; P = .55). After adjusting for age, the odds ratio for adverse birth outcome after receiving at least 1 dose of anthrax vaccination was 0.9 (95% CI, 0.4-2.4; P = .88). However, this study did not have sufficient power to detect adverse birth outcomes.ConclusionAnthrax vaccination had no effect on pregnancy and birth rates or adverse birth outcomes.

Antimicrobial sensitivity in enterobacteria from AIDS patients, Zambia.

Abstract: Mycoplasma contamination of the licensed anthrax vaccine administered to military personnel has been suggested as a possible cause of Persian Gulf illness. Vaccine samples tested by nonmilitary laboratories were negative for viable mycoplasma and mycoplasma DNA and did not support its survival. Mycoplasma contamination of anthrax vaccine should not be considered a possible cause of illness.

Anthrax vaccination and joint related adverse reactions in light of biological warfare scenarios.

Abstract: Objectives: The purpose of this analysis was to evaluate anthrax vaccine (AVA) and joint related adverse reactions based upon analysis of the VAERS database in light of the current possibility of the use of anthrax as a biological warfare agent. Methods: A certified copy of the VAERS database was obtained from the CDC. In this study, we conducted a retrospective analysis using Microsoft Access for all joint attributed adverse reactions reported following anthrax vaccination. The employment of chisquare analysis determined if the elevated incidence rates of associated adverse reactions in anthrax vaccine recipients were statistically significant. Results: Our analysis shows a very large and statistically significant increase in joint symptoms following vaccination with AVA when compared to our control population consisting of adverse joint reactions reported following vaccination with hepatitis A vaccine and Td vaccine. Conclusion: We believe that civilian doctors need to become familiar with the adverse reactions that can be expected to follow the use of AVA. Both civilian and military doctors need to be vigilant in reporting all such reactions to VAERS, so that more information can be gathered about AVA. We also 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. It should also be kept in mind that the widespread use of anthrax vaccination may cause potential producers of biological weapons and terrorists to seek to produce anthrax strains that are not neutralized by the current vaccine.

The Anthrax Vaccine Program: An Analysis of the CDC's Recommendations for Vaccine Use

Abstract: The anthrax vaccine was never proved to be safe and effective. It is one cause of Gulf War illnesses, and recent vaccinees report symptoms resembling Gulf War illnesses. The vaccine's production has been substandard. Without adequate evaluation, the Food and Drug Administration recently approved (retrospectively) significant changes made to the vaccine's composition since 1990. The vaccine's mandatory use for inhalation anthrax is "off-label." A skewed review of the vaccine literature by the Centers for Disease Control and Prevention (CDC) led to remunerative collaborative research with the army, involving civilian volunteers. Despite acknowledging possible fetal harm, the CDC offered the vaccine to children and pregnant women. New trends could weaken prelicensure efficacy and safety review of medical products intended for biodefense and avoid manufacturer liability for their use.

Call-tracking data and the public health response to bioterrorism-related anthrax.

Abstract: After public notification of confirmed cases of bioterrorism-related anthrax, the Centers for Disease Control and Prevention’s Emergency Operations Center responded to 11,063 bioterrorism-related telephone calls from October 8 to November 11, 2001. Most calls were inquiries from the public about anthrax vaccines (58.4%), requests for general information on bioterrorism prevention (14.8%), and use of personal protective equipment (12.0%); 882 telephone calls (8.0%) were referred to the state liaison team for follow-up investigation. Of these, 226 (25.6%) included reports of either illness clinically confirmed to be compatible with anthrax or direct exposure to an environment known to be contaminated with Bacillus anthracis. The remaining 656 (74.4%) included no confirmed illness but reported exposures to “suspicious” packages or substances or the receipt of mail through a contaminated facility. Emergency response staff must handle high call volumes following suspected or actual bioterrorist attacks. Standardized health communication protocols that address contact with unknown substances, handling of suspicious mail, and clinical evaluation of suspected cases would allow more efficient follow-up investigations of clinically compatible cases in high-risk groups.

Vaccination against anthrax

Abstract: Methods are disclosed for immunizing a mammal against B. anthracis using a composition of pure recombinant Protective Antigen (rPA), optionally in combination with truncated Lethal Factor polypeptide (LFn). Formulations of the pure rPA immunogen have little or no reactogenicity and therefore may be administered to a mammalian subject in very high doses of 50 μg to 1000 μg or more rPA, which is at least four times the amount of PA included per dose in conventional anthrax vaccines. Preferred immunogenic compositions are free of adjuvant and other undesired components, further enhancing the effectiveness and safety of the compositions. Methods for preparing the immunogenic compositions and for purifying rPA and LFn polypeptides also are disclosed.

Responding to the threat of bioterrorism: a microbial ecology perspective--the case of anthrax.

Abstract: Anthrax is a disease of herbivores caused by the gram-positive bacterium Bacillus anthracis. It can affect cattle, sheep, swine, horses and various species of wildlife. The routes for the spread among wildlife are reviewed. There are three kinds of human anthrax – inhalation, cutaneous, and intestinal anthrax – which differ in their routes of infection and outcomes. In the United States, confirmation of cases is made by the isolation of B. anthracis and by biochemical tests. Vaccination is not recommended for the general public; civilians who should be vaccinated include those who, in their work places, come in contact with products potentially contaminated with B. anthracis spores, and people engaged in research or diagnostic activities. After September 11, 2001, there were bioterrorism anthrax attacks in the United States: anthrax-laced letters sent to multiple locations were the source of infectious B. anthracis. The US Postal Service issued recommendations to prevent the danger of hazardous exposure to the bacterium. B. anthracis spores can spread easily and persist for very long times, which makes decontamination of buildings very difficult. Early detection, rapid diagnosis, and well-coordinated public health response are the key to minimizing casualties. The US Government is seeking new ways to deter bioterrorism, including a tighter control of research on infectious agents, even though pathogens such as B. anthracis are widely spread in nature and easy to grow. It is necessary to define the boundary between defensive and offensive biological weapons research. Deterring bioterrorism should not restrict critical scientific research.

Passive hyperimmune antibody therapy in the treatment of anthrax

Abstract: A method of treatment of severe anthrax infection particularly inhalation pneumonia or gastrointestinal anthrax antigen by the passive transfer to infected patients of plasma or plasma fractionated derivatives, such as gammaglobulins or antibodies, monoclonal or polyclonal, with high titer neutralizing antibodies against Bacillus anthracis or its toxins. The plasma or fractionated plasma derivatives are derived from previously vaccinated individuals with anthrax vaccine, or any antigen or toxin antigen of Bacillus anthracis, including protective antigen (PA), lethal factor (LF) and/or oedema factor (OF).

Delayed-type hypersensitivity reaction to anthrax vaccine.

Abstract: The Anthrax Vaccine Immunization Program is a Department of Defense initiative to protect military personnel against the threat of anthrax. Surveillance for adverse events associated with anthrax vaccination has shown that mild local reactions are not uncommon while systemic reactions are extremely rare. We present a case of a 26-year-old male with delayed-type hypersensitivity after two doses of anthrax vaccine.

Old and new prescriptions for infectious diseases and the newest recipes for biomedical products in plants

Abstract: The three antiviral vaccines discovered in the 18th century (smallpox), 19th century (rabies), and 20th century (polio) share a common feature: none would ever be licensed today for human vaccination. Yet Jenner's smallpox vaccine led to the eradication of smallpox, Pasteur's rabies vaccine represented the first successful post-exposure treatment of people bitten by rabid animals, and polio vaccine administered since its discovery in 1950 is leading to the eradication of polio (in the years 2004-2005) from the earth. However, in the case of rabies, efforts at complete eradication are unrealistic, despite the availability of a very effective vaccine, since rabies, unlike smallpox and polio, is not limited to humans and can infect all domestic and wild mammalian species. Rabies is probably the oldest known infectious disease, yet knowledge of the virus and the disease is far from complete. For instance, the appearance of 24 cases of "cryptic" rabies in the USA, i.e. cases not associated with any bite or scratch, with an incubation period in humans extending 6-8 years, is a puzzling phenomenon that cannot be readily explained. On the other hand, rabies is one of the few strictly neuronal infections and, as such, is an excellent model for the study of neurotropic virus distribution in the brain. Apoptosis induced by a rabies strain expressing high levels of glycoprotein spreads much more slowly through brain tissue than that induced by strains producing lower glycoprotein levels. Attenuated rabies virus constructed to express twice the normal glycoprotein levels is also an excellent antigen for induction of immune responses in the host. Foreign antigens using this vector may also produce highly immunogenic vaccines. Global approach to immunization. Those monitoring the spread of AIDS in many parts of the world know that cost of treatment is one of the major problems in combating the disease. Vaccines against HIV face the same problem. In general, the price of vaccines and sera is exorbitant for the afflicted population in developing countries. In addition, the dearth of syringes, the unavailability of nurses and doctors to administer multiple vaccine injections, and other factors in these countries require a drastic change in current vaccine production approaches. About 12 years ago, plants became vehicles to produce biomedical reagents. Plants can be exposed directly to a construct containing a foreign gene and Agrobacterium to create a transgenic plant that, over several generations, produces the desired product. Alternatively, plants infected with a plant virus (e.g. alfalfa mosaic virus) fused with a foreign gene can propagate the foreign antigen as the virus multiplies. Extraction of the plant virus followed by purification provides the desired biomedical product. Our use of either of these systems has led to the creation of plants producing vaccines, sera, hormones, and other biological reagents. In two clinical trials at the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznan (Poland), volunteers who ingested lettuce expressing hepatitis B vaccine showed hepatitis B antibodies in their sera. In another trial carried out at the Biotechnology Foundation Laboratories in Philadelphia (USA), volunteers ingesting a spinach-rabies vaccine showed an immunological priming effect, since only one injection of commercially available rabies vaccine significantly raised the level of rabies-specific antibodies. Vaccines against HIV gp120 and Tat have been produced in spinach, and a construct of gp120 with the CD4 receptor is now being adapted to this plant. Two types of antibodies against rabies and against colorectal cancer are being produced in tobacco and in lettuce. The suboptimal quality of the currently available anthrax vaccine prompted our efforts to produce the anthrax protective antigen (PA) in tobacco and lettuce. Quite clearly, plants will play a prominent role in producing a variety of biomedical reagents in the future.