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Annals of Saudi Medicine 2005Anthrax, an uncommon disease in humans, is caused by a large bacterium, Bacillus anthracis. The risk of inhalation infection is the main indication for anthrax... (Review)
Review
Anthrax, an uncommon disease in humans, is caused by a large bacterium, Bacillus anthracis. The risk of inhalation infection is the main indication for anthrax vaccination. Pre-exposure vaccination is provided by an acellular vaccine (anthrax vaccine adsorbed or AVA), which contains anthrax toxin elements and results in protective immunity after 3 to 6 doses. Anthrax vaccine precipitated (AVP) is administered at primovaccination in 3 doses with a booster dose after 6 months. To evoke and maintain protective immunity, it is necessary to administer a booster dose once at 12 months. In Russia, live spore vaccine (STI) has been used in a two-dose schedule. Current anthrax vaccines show considerable local and general reactogenicity (erythema, induration, soreness, fever). Serious adverse reactions occur in about 1% of vaccinations. New second-generation vaccines in current research programs include recombinant live vaccines and recombinant sub-unit vaccines.
Topics: Adverse Drug Reaction Reporting Systems; Animals; Anthrax; Anthrax Vaccines; Bioterrorism; Humans; Immunization, Secondary; United States
PubMed: 15977694
DOI: 10.5144/0256-4947.2005.143 -
Birth Defects Research Jan 2021The AV7909 vaccine, consists of the Anthrax Vaccine Adsorbed (AVA) bulk drug substance and the immunostimulatory Toll-like receptor 9 agonist oligodeoxynucleotide...
The AV7909 vaccine, consists of the Anthrax Vaccine Adsorbed (AVA) bulk drug substance and the immunostimulatory Toll-like receptor 9 agonist oligodeoxynucleotide adjuvant CPG 7909. The purpose of this research was to evaluate the potential maternal, reproductive, and developmental toxicity of AV7909 in rats to support licensure for use in women of childbearing potential. Groups of first generation (F ) female Sprague Dawley rats were dosed by intramuscular injection with water for injection, adjuvant or AV7909 at a volume of 0.5 ml/dose. Each rat received three vaccinations: 14 days prior to start of the mating period, on the first day of the mating period and on gestation day (GD) 7. There was no maternal mortality. Body weights, weight gain, and food consumption were comparable between groups. Findings in F females were limited to transient injection site edema and nodules consistent with immunostimulatory effects of the vaccine and adjuvant. Administration of AV7909 did not affect mating, fertility, pregnancy, embryo-fetal viability, growth, or morphologic development, parturition, maternal care of offspring or postnatal survival, growth, or development. There was no evidence of systemic inflammation in pregnant rats, based on evaluation of serum concentrations of the acute phase proteins alpha-2-macroglobulin and alpha-1-acid glycoprotein on GD 21. Anthrax lethal toxin-neutralizing antibodies were detected in AV7909-vaccinated F females. The antibodies were also detected in the sera of fetuses and F pups. Exposure of the fetuses and pups to maternally derived anthrax lethal toxin-neutralizing antibodies was not associated with developmental toxicity.
Topics: Animals; Anthrax; Anthrax Vaccines; Antibodies, Neutralizing; Female; Pregnancy; Rats; Rats, Sprague-Dawley; Reproduction
PubMed: 33067910
DOI: 10.1002/bdr2.1815 -
Cureus Mar 2023In this paper, we reveal the anthrax weaponization in the Soviet Union and its impact on biowarfare research, technology, and public health that resulted in the... (Review)
Review
In this paper, we reveal the anthrax weaponization in the Soviet Union and its impact on biowarfare research, technology, and public health that resulted in the development of the first Soviet Anthrax vaccine and the subsequent vaccination of animals and humans en masse. We assume that there are cases that a biowarfare technology was incorporated into the civilian industry and benefited public health. However, the legacy of bioweapons today still poses an asymmetric threat to public health and safety.
PubMed: 37123719
DOI: 10.7759/cureus.36800 -
Current Topics in Microbiology and... 2009The threat of pandemic influenza and other public health needs motivate the development of better vaccine delivery systems. To address this need, microneedles have been... (Review)
Review
The threat of pandemic influenza and other public health needs motivate the development of better vaccine delivery systems. To address this need, microneedles have been developed as micron-scale needles fabricated using low-cost manufacturing methods that administer vaccine into the skin using a simple device that may be suitable for self-administration. Delivery using solid or hollow microneedles can be accomplished by (1) piercing the skin and then applying a vaccine formulation or patch onto the permeabilized skin, (2) coating or encapsulating vaccine onto or within microneedles for rapid, or delayed, dissolution and release in the skin, and (3) injection into the skin using a modified syringe or pump. Extensive clinical experience with smallpox, TB, and other vaccines has shown that vaccine delivery into the skin using conventional intradermal injection is generally safe and effective and often elicits the same immune responses at lower doses compared to intramuscular injection. Animal experiments using microneedles have shown similar benefits. Microneedles have been used to deliver whole, inactivated virus; trivalent split antigen vaccines; and DNA plasmids encoding the influenza hemagglutinin to rodents, and strong antibody responses were elicited. In addition, ChimeriVax-JE against yellow fever was administered to nonhuman primates by microneedles and generated protective levels of neutralizing antibodies that were more than seven times greater than those obtained with subcutaneous delivery; DNA plasmids encoding hepatitis B surface antigen were administered to mice and antibody and T cell responses at least as strong as hypodermic injections were generated; recombinant protective antigen of Bacillus anthracis was administered to rabbits and provided complete protection from lethal aerosol anthrax spore challenge at a lower dose than intramuscular injection; and DNA plasmids encoding four vaccinia virus genes administered to mice in combination with electroporation generated neutralizing antibodies that apparently included both Th1 and Th2 responses. Dose sparing with microneedles was specifically studied in mice with the model vaccine ovalbumin. At low dose (1 microg), specific antibody titers from microneedles were one order of magnitude greater than subcutaneous injection and two orders of magnitude greater than intramuscular injection. At higher doses, antibody responses increased for all delivery methods. At the highest levels (20-80 microg), the route of administration had no significant effect on the immune response. Concerning safety, no infections or other serious adverse events have been observed in well over 1,000 microneedle insertions in human and animal subjects. Bleeding generally does not occur for short microneedles (<1 mm). Highly localized, mild, and transient erythema is often observed. Microneedle pain has been reported as nonexistent to mild, and always much less than a hypodermic needle control. Overall, these studies suggest that microneedles may provide a safe and effective method of delivering vaccines with the possible added attributes of requiring lower vaccine doses, permitting low-cost manufacturing, and enabling simple distribution and administration.
Topics: Animals; Drug Delivery Systems; Humans; Influenza Vaccines; Injections, Intradermal; Needles; Vaccination
PubMed: 19768415
DOI: 10.1007/978-3-540-92165-3_18 -
BMC Microbiology Mar 2021Anthrax and smallpox are high-risk infectious diseases, and considered as potential agents for bioterrorism. To develop an effective countermeasure for these diseases,...
BACKGROUND
Anthrax and smallpox are high-risk infectious diseases, and considered as potential agents for bioterrorism. To develop an effective countermeasure for these diseases, we constructed a bivalent vaccine against both anthrax and smallpox by integrating a gene encoding protective antigen (PA) of Bacillus anthracis to the genome of the attenuated vaccinia virus strain, KVAC103.
RESULTS
Immunization with this bivalent vaccine induced antibodies against both PA and vaccinia virus in a mouse model. We also observed that the efficacy of this vaccine can be enhanced by combined immunization with immunoadjuvant-expressing KVAC103. Mouse groups co-immunized with PA-expressing KVAC103 and either interleukin-15 (IL-15) or cholera toxin subunit A (CTA1)-expressing KVAC103 showed increased anti-PA IgG titer and survival rate against B. anthracis spore challenge compared to the group immunized with PA-expressing KVAC103 alone.
CONCLUSIONS
We demonstrated that the attenuated smallpox vaccine KVAC103 is an available platform for a multivalent vaccine and co-immunization of immunoadjuvants can improve vaccine performance.
Topics: Adjuvants, Immunologic; Animals; Anthrax; Antibodies, Bacterial; Antibodies, Viral; Bacillus anthracis; Mice; Smallpox; Vaccines, Attenuated; Vaccines, Combined; Vaccines, Synthetic; Vaccinia virus
PubMed: 33685392
DOI: 10.1186/s12866-021-02121-5 -
Expert Review of Vaccines Sep 2016Anthrax Vaccine Adsorbed (AVA, BioThrax™) is the only Food and Drug Administration (FDA) approved vaccine for the prevention of anthrax in humans. Recent improvements... (Review)
Review
Anthrax Vaccine Adsorbed (AVA, BioThrax™) is the only Food and Drug Administration (FDA) approved vaccine for the prevention of anthrax in humans. Recent improvements in pre-exposure prophylaxis (PrEP) use of AVA include intramuscular (IM) administration and simplification of the priming series to three doses over 6 months. Administration IM markedly reduced the frequency, severity and duration of injection site reactions. Refinement of animal models for inhalation anthrax, identification of immune correlates of protection and cross-species modeling have created opportunities for reductions in the PrEP booster schedule and were pivotal in FDA approval of a post-exposure prophylaxis (PEP) indication. Clinical and nonclinical studies of accelerated PEP schedules and divided doses may provide prospects for shortening the PEP antimicrobial treatment period. These data may assist in determining feasibility of expanded coverage in a large-scale emergency when vaccine demand may exceed availability. Enhancements to the AVA formulation may broaden the vaccine's PEP application.
Topics: Animals; Anthrax; Anthrax Vaccines; Humans; Immunization Schedule; Injections, Intramuscular; Models, Animal; Post-Exposure Prophylaxis; Pre-Exposure Prophylaxis
PubMed: 26942655
DOI: 10.1586/14760584.2016.1162104 -
Diagnostics (Basel, Switzerland) Mar 2023Anthrax is one of the most important zoonotic diseases which primarily infects herbivores and occasionally humans. The etiological agent is which is a Gram-positive,... (Review)
Review
Anthrax is one of the most important zoonotic diseases which primarily infects herbivores and occasionally humans. The etiological agent is which is a Gram-positive, aerobic, spore-forming, nonmotile, rod-shaped bacillus. The spores are resistant to environmental conditions and remain viable for a long time in contaminated soil, which is the main reservoir for wild and domestic mammals. Infections still occur in low-income countries where they cause suffering and economic hardship. Humans are infected by contact with ill or dead animals, contaminated animal products, directly exposed to the spores in the environment or spores released as a consequence of a bioterrorist event. Three classical clinical forms of the disease, cutaneous, gastrointestinal and inhalation, are seen, all of which can potentially lead to sepsis or meningitis. A new clinical form in drug users has been described recently and named "injectional anthrax" with high mortality (>33%). The symptoms of anthrax in the early stage mimics many diseases and as a consequence it is important to confirm the diagnosis using a bacterial culture or a molecular test. With regards to treatment, human isolates are generally susceptible to most antibiotics with penicillin G and amoxicillin as the first choice, and ciprofloxacin and doxycycline serving as alternatives. A combination of one or more antibiotics is suggested in systemic anthrax. Controlling anthrax in humans depends primarily on effective control of the disease in animals. Spore vaccines are used in veterinary service, and an acellular vaccine is available for humans but its use is limited.
PubMed: 36980364
DOI: 10.3390/diagnostics13061056 -
American Journal of Public Health Nov 2007The Centers for Disease Control and Prevention has classified Bacillus anthracis, the causative organism of anthrax, as a category A potential bioterrorism agent. There... (Review)
Review
The Centers for Disease Control and Prevention has classified Bacillus anthracis, the causative organism of anthrax, as a category A potential bioterrorism agent. There are critical shortcomings in the US anthrax vaccine program. Rather than depending on the private sector, the government must assume direct production of anthrax vaccine. The development of a capacity capable of preemptive immunization of the public against anthrax should be considered.
Topics: Animals; Anthrax; Anthrax Vaccines; Anti-Bacterial Agents; Biotechnology; Bioterrorism; Cricetinae; Drug Design; Federal Government; Health Policy; Humans; Mass Vaccination; Mesocricetus; National Academies of Science, Engineering, and Medicine, U.S., Health and Medicine Division; Politics; Private Sector; Public Health; Public Policy; United States; United States Dept. of Health and Human Services
PubMed: 17901434
DOI: 10.2105/AJPH.2006.102749 -
MMWR. Recommendations and Reports :... Nov 2023Bacillus anthracis spores if resources become limited or a multidrug-resistant B. anthracis strain is used (Hendricks KA, Wright ME, Shadomy SV, et al.; Workgroup on...
THIS REPORT UPDATES PREVIOUS CDC GUIDELINES AND RECOMMENDATIONS ON PREFERRED PREVENTION AND TREATMENT REGIMENS REGARDING NATURALLY OCCURRING ANTHRAX. ALSO PROVIDED ARE A WIDE RANGE OF ALTERNATIVE REGIMENS TO FIRST-LINE ANTIMICROBIAL DRUGS FOR USE IF PATIENTS HAVE CONTRAINDICATIONS OR INTOLERANCES OR AFTER A WIDE-AREA AEROSOL RELEASE OF
Bacillus anthracis spores if resources become limited or a multidrug-resistant B. anthracis strain is used (Hendricks KA, Wright ME, Shadomy SV, et al.; Workgroup on Anthrax Clinical Guidelines. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20:e130687; Meaney-Delman D, Rasmussen SA, Beigi RH, et al. Prophylaxis and treatment of anthrax in pregnant women. Obstet Gynecol 2013;122:885-900; Bradley JS, Peacock G, Krug SE, et al. Pediatric anthrax clinical management. Pediatrics 2014;133:e1411-36). Specifically, this report updates antimicrobial drug and antitoxin use for both postexposure prophylaxis (PEP) and treatment from these previous guidelines best practices and is based on systematic reviews of the literature regarding 1) in vitro antimicrobial drug activity against B. anthracis; 2) in vivo antimicrobial drug efficacy for PEP and treatment; 3) in vivo and human antitoxin efficacy for PEP, treatment, or both; and 4) human survival after antimicrobial drug PEP and treatment of localized anthrax, systemic anthrax, and anthrax meningitis.
CHANGES FROM PREVIOUS CDC GUIDELINES AND RECOMMENDATIONS INCLUDE AN EXPANDED LIST OF ALTERNATIVE ANTIMICROBIAL DRUGS TO USE WHEN FIRST-LINE ANTIMICROBIAL DRUGS ARE CONTRAINDICATED OR NOT TOLERATED OR AFTER A BIOTERRORISM EVENT WHEN FIRST-LINE ANTIMICROBIAL DRUGS ARE DEPLETED OR INEFFECTIVE AGAINST A GENETICALLY ENGINEERED RESISTANT
B. anthracis strain. In addition, these updated guidelines include new recommendations regarding special considerations for the diagnosis and treatment of anthrax meningitis, including comorbid, social, and clinical predictors of anthrax meningitis. The previously published CDC guidelines and recommendations described potentially beneficial critical care measures and clinical assessment tools and procedures for persons with anthrax, which have not changed and are not addressed in this update. In addition, no changes were made to the Advisory Committee on Immunization Practices recommendations for use of anthrax vaccine (Bower WA, Schiffer J, Atmar RL, et al. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices, 2019. MMWR Recomm Rep 2019;68[No. RR-4]:1-14). The updated guidelines in this report can be used by health care providers to prevent and treat anthrax and guide emergency preparedness officials and planners as they develop and update plans for a wide-area aerosol release of B. anthracis.
Topics: Adult; Humans; Female; Child; Pregnancy; United States; Anthrax; Anthrax Vaccines; Bacillus anthracis; Anti-Infective Agents; Antitoxins; Centers for Disease Control and Prevention, U.S.; Aerosols; Meningitis
PubMed: 37963097
DOI: 10.15585/mmwr.rr7206a1 -
Vaccines Feb 2024Vaccination against is the best preventive measure against the development of deadly anthrax disease in the event of exposure to anthrax either as a bioweapon or in its... (Review)
Review
Vaccination against is the best preventive measure against the development of deadly anthrax disease in the event of exposure to anthrax either as a bioweapon or in its naturally occurring form. Anthrax vaccines, however, have historically been plagued with controversy, particularly related to their safety. Fortunately, recent improvements in anthrax vaccines have been shown to confer protection with reduced short-term safety concerns, although questions about long-term safety remain. Here, we (a) review recent and ongoing advances in anthrax vaccine development, (b) emphasize the need for thorough characterization of current (and future) vaccines, (c) bring to focus the importance of host immunogenetics as the ultimate determinant of successful antibody production and protection, and (d) discuss the need for the systematic, active, and targeted monitoring of vaccine recipients for possible Chronic Multisymptom Illness (CMI).
PubMed: 38400142
DOI: 10.3390/vaccines12020159