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Expert Opinion on Biological Therapy Dec 2020Vaccines and therapeutic antibodies are the most crucial components of anthrax prophylaxis (pre- and post-exposure) and treatment. The improvement in the availability... (Review)
Review
INTRODUCTION
Vaccines and therapeutic antibodies are the most crucial components of anthrax prophylaxis (pre- and post-exposure) and treatment. The improvement in the availability and safety profile of vaccines and the therapeutic antibodies has helped immensely in reducing the worldwide burden of anthrax.
AREAS COVERED
Current recommendations for anthrax prophylaxis and control, vaccines and therapeutic antibodies, the recent endeavors, particularly, made after 2010 toward making them safer and more efficacious along with our opinion on its future course. Primarily, PubMed and Europe PMC were searched to cover the recent developments in the above-indicated areas.
EXPERT OPINION
Some key existing lacunae in our understanding of the working of biologicals-based anthrax-control measures, ., vaccines and therapeutic antibodies, should be addressed to improve their overall stability, safety profile, and efficacy. The identification of novel inhibitors targeting different key-molecules and vital-steps contributing to the overall anthrax pathophysiology could make a difference in anthrax control.
Topics: Animals; Anthrax; Anthrax Vaccines; History, 20th Century; History, 21st Century; Humans; Post-Exposure Prophylaxis; Pre-Exposure Prophylaxis
PubMed: 32729741
DOI: 10.1080/14712598.2020.1801626 -
Current Medicinal Chemistry 2011Aluminum is an experimentally demonstrated neurotoxin and the most commonly used vaccine adjuvant. Despite almost 90 years of widespread use of aluminum adjuvants,...
Aluminum is an experimentally demonstrated neurotoxin and the most commonly used vaccine adjuvant. Despite almost 90 years of widespread use of aluminum adjuvants, medical science's understanding about their mechanisms of action is still remarkably poor. There is also a concerning scarcity of data on toxicology and pharmacokinetics of these compounds. In spite of this, the notion that aluminum in vaccines is safe appears to be widely accepted. Experimental research, however, clearly shows that aluminum adjuvants have a potential to induce serious immunological disorders in humans. In particular, aluminum in adjuvant form carries a risk for autoimmunity, long-term brain inflammation and associated neurological complications and may thus have profound and widespread adverse health consequences. In our opinion, the possibility that vaccine benefits may have been overrated and the risk of potential adverse effects underestimated, has not been rigorously evaluated in the medical and scientific community. We hope that the present paper will provide a framework for a much needed and long overdue assessment of this highly contentious medical issue.
Topics: Adjuvants, Immunologic; Aluminum; Animals; Anthrax Vaccines; Autoimmune Diseases of the Nervous System; Body Burden; Child; Child, Preschool; Humans; Infant; Placebos; Vaccines
PubMed: 21568886
DOI: 10.2174/092986711795933740 -
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 -
Human Vaccines Mar 2009The original license for production of the anthrax vaccine, Anthrax Vaccine Adsorbed (AVA), was issued in 1970. Since that time, over 8 million AVA immunizations have... (Review)
Review
The original license for production of the anthrax vaccine, Anthrax Vaccine Adsorbed (AVA), was issued in 1970. Since that time, over 8 million AVA immunizations have been administered to 2+ million individuals. In 2002, the National Academy of Sciences, Institute of Medicine, reviewed the safety and efficacy of AVA. They concluded that the vaccine is acceptably safe and effective in protecting humans against anthrax. The vaccine should protect people against all known strains of anthrax bacteria, as well as against any strains that might be created by potential terrorists or others. Although the Institute of Medicine concluded that AVA was reasonably safe, they noted that it is fairly common for people to experience local reactions (e.g., redness and swelling at the injection site) and for a smaller number to experience systemic reactions such as fever and malaise, within hours or days of vaccination. Results of animal studies done previously and subsequent to this report are generally in agreement. For instance, AVA vaccination increases the level of anthrax anti-protective antigen IgG (anti-PA IgG), which is thought to be one possible correlate of protection (although absolute protective concentrations have not been identified in humans). Anthrax lethal factor neutralization has also been identified as possibly being an important additional correlate of immunity. Future vaccine research efforts include developing a recombinant anthrax vaccine and anthrax monoclonal antibodies to block the anthrax toxin(s). It is projected that the next-generation vaccine will elicit a markedly increased anti-anthrax immune response within a shorter time period and consequently, will enable the easier inoculations of individuals working within high-risk areas.
Topics: Animals; Anthrax; Anthrax Vaccines; Antibodies, Bacterial; Antitoxins; Drug-Related Side Effects and Adverse Reactions; Fever; Humans; Immunoglobulin G; Neutralization Tests; Skin Diseases
PubMed: 19270504
DOI: 10.4161/hv.5.3.7308 -
Immunology and Allergy Clinics of North... Nov 2003Anthrax can be a deadly disease if treatment does not begin early in the course of infection. An effective vaccine has been available in the United States since 1970,... (Review)
Review
Anthrax can be a deadly disease if treatment does not begin early in the course of infection. An effective vaccine has been available in the United States since 1970, although it was not used widely until 1998. A comprehensive, peer-reviewed evaluation by the National Academy of Sciences affirmed the findings of multiple previous independent panels that found that the US-licensed anthrax vaccine is safe and effective.
Topics: Anthrax; Anthrax Vaccines; Bioterrorism; Humans
PubMed: 14753388
DOI: 10.1016/s0889-8561(03)00093-6 -
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 -
Molecular Aspects of Medicine Dec 2009The biological attack conducted through the US postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to... (Review)
Review
The biological attack conducted through the US postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to one understood to exist throughout our society. The expansion of the threatened population placed greater emphasis on the reexamination of how we vaccinate against Bacillus anthracis. The currently-licensed Anthrax Vaccine, Adsorbed (AVA) and Anthrax Vaccine, Precipitated (AVP) are capable of generating a protective immune response but are hampered by shortcomings that make their widespread use undesirable or infeasible. Efforts to gain US Food and Drug Administration (FDA) approval for licensure of a second generation recombinant protective antigen (rPA)-based anthrax vaccine are ongoing. However, this vaccine's reliance on the generation of a humoral immune response against a single virulence factor has led a number of scientists to conclude that the vaccine is likely not the final solution to optimal anthrax vaccine design. Other vaccine approaches, which seek a more comprehensive immune response targeted at multiple components of the B. anthracis organism, are under active investigation. This review seeks to summarize work that has been done to build on the current PA-based vaccine methodology and to evaluate the search for future anthrax prophylaxis strategies.
Topics: Adjuvants, Immunologic; Animals; Anthrax; Anthrax Vaccines; Antibodies, Bacterial; Antigens, Bacterial; Bacillus anthracis; Bacterial Proteins; Bacterial Toxins; Drug Approval; Humans; Recombinant Proteins; Spores, Bacterial; Vaccination; Vaccines, DNA
PubMed: 19729034
DOI: 10.1016/j.mam.2009.08.006 -
Emerging Microbes & Infections Dec 2023Pulmonary anthrax is the most fatal clinical form of anthrax and currently available injectable vaccines do not provide adequate protection against it. Hence,...
Pulmonary anthrax is the most fatal clinical form of anthrax and currently available injectable vaccines do not provide adequate protection against it. Hence, next-generation vaccines that effectively induce immunity against pulmonary anthrax are urgently needed. In the present study, we prepared an attenuated and low protease activity strain A16R-5.1 by deleting five of its extracellular protease activity-associated genes and its gene through the CRISPR-Cas9 genome editing system. This mutant strain was then used to formulate a lethal toxin (LeTx)-free culture supernatant extract (CSE) anthrax vaccine, of which half was protective antigen (PA). We generated liquid, powder, and powder reconstituted formulations that could be delivered by aerosolized intratracheal inoculation. All of them induced strong humoral, cellular, and mucosal immune responses. The vaccines also produced LeTx neutralizing antibodies and conferred full protection against the lethal aerosol challenges of Pasteur II spores in mice. Compared to the recombinant PA vaccine, the CSE anthrax vaccine with equal PA content provided superior immunoprotection against pulmonary anthrax. The preceding results suggest that the CSE anthrax vaccine developed herein is suitable and scalable for use in inhalational immunization against pulmonary anthrax.
Topics: Mice; Animals; Anthrax; Anthrax Vaccines; Antigens, Bacterial; Powders; Bacillus anthracis; Vaccines, Synthetic; Peptide Hydrolases; Antibodies, Bacterial
PubMed: 36920800
DOI: 10.1080/22221751.2023.2191741 -
Human Vaccines & Immunotherapeutics Mar 2021The manufacture of the UK Anthrax vaccine (AVP) focuses on the production of Protective Antigen (PA) from the Sterne strain. Although used for decades, several of AVP's...
The manufacture of the UK Anthrax vaccine (AVP) focuses on the production of Protective Antigen (PA) from the Sterne strain. Although used for decades, several of AVP's fundamental properties are poorly understood, including its exact composition, the extent to which proteins other than PA may contribute to protection, and whether the degree of protection varies between individuals.This study involved three innovative investigations. Firstly, the composition of AVP was analyzed using liquid chromatography tandem mass-spectrometry (LC-MS/MS), requiring the development of a novel desorption method for releasing proteins from the vaccine's aluminum-containing adjuvant. Secondly, computational MHC-binding predictions using NetMHCIIpan were made for the eight most abundant proteins of AVP, for the commonest HLA alleles in multiple ethnic groups, and for multiple strains. Thirdly, antibody levels and toxin neutralizing antibody (TNA) levels were measured in sera from AVP human vaccinees for both PA and Lethal Factor (LF).It was demonstrated that AVP is composed of at least 138 proteins, including PA (65%), LF (8%) and Edema Factor (EF) (3%), using LC-MS/MS. NetMHCIIpan predicted that peptides from all eight abundant proteins are likely to be presented to T cells, a pre-requisite for protection; however, the number of such peptides varied considerably between different HLA alleles.These analyses highlight two important properties of the AVP vaccine that have not been established previously. Firstly, the effectiveness of AVP within humans may not depend on PA alone; there is compelling evidence to suggest that LF has a protective role, with computational predictions suggesting that additional proteins may be important for individuals with specific HLA allele combinations. Secondly, in spite of differences in the sequences of key antigenic proteins from different strains, these are unlikely to affect the cross-strain protection afforded by AVP.
Topics: Anthrax; Anthrax Vaccines; Antibodies, Bacterial; Antigens, Bacterial; Bacillus anthracis; Chromatography, Liquid; Humans; Immunogenicity, Vaccine; Tandem Mass Spectrometry; United Kingdom
PubMed: 32897798
DOI: 10.1080/21645515.2020.1799668 -
Current Drug Delivery 2020Anthrax is a lethal bacterial disease caused by gram-positive bacterium Bacillus anthracis and vaccination is a desirable method to prevent anthrax infections. In the...
PURPOSE
Anthrax is a lethal bacterial disease caused by gram-positive bacterium Bacillus anthracis and vaccination is a desirable method to prevent anthrax infections. In the present study, DNA vaccine encoding a protective antigen of Bacillus anthracis was prepared and we investigated the influence of DNA electrotransfer in the skin on the induced immune response and biodistribution.
METHODS AND RESULTS
The tdTomato reporter gene for the whole animal in vivo imaging was used to assess gene transfer efficiency into the skin as a function of electrical parameters. Compared to that with 25 V, the transgene expression of red fluorescent protein increased significantly when a voltage of 90 V was used. Delivery of DNA vaccines expressing Bacillus anthracis protective antigen domain 4 (PAD4) with an applied voltage of 90 V induced robust PA-D4-specific antibody responses. In addition, the in vivo fate of anthrax DNA vaccine was studied after intradermal administration into the mouse. DNA plasmids remained at the skin injection site for an appropriate period of time after immunization. Intradermal administration of DNA vaccine resulted in detection in various organs (viz., lung, heart, kidney, spleen, brain, and liver), although the levels were significantly reduced.
CONCLUSION
Our results offer important insights into how anthrax DNA vaccine delivery by intradermal electroporation affects the immune response and biodistribution of DNA vaccine. Therefore, it may provide valuable information for the development of effective DNA vaccines against anthrax infection.
Topics: Animals; Anthrax Vaccines; Antibodies, Bacterial; Antigens, Bacterial; Bacillus anthracis; Bacterial Toxins; Electroporation; Female; Gene Expression; Genes, Reporter; Immunoglobulin G; Injections, Intradermal; Luminescent Proteins; Mice, Inbred BALB C; Plasmids; Skin; Tissue Distribution; Vaccines, DNA; Red Fluorescent Protein
PubMed: 32286944
DOI: 10.2174/1567201817666200414144550