Search Results (43)

Background/Objectives: Bacterial vaccines were first developed and used in the late 1800s to prevent chicken cholera and anthrax. Bacterial pneumonia vaccines were widely used during the 1918 influenza pandemic, despite the influenza A/H1N1 virus not yet being identified. Studies showed that bacterial pathogens, including Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus pyogenes, contributed significantly to fatal secondary bacterial pneumonias during the pandemic. In this study, we aimed to characterize the microbial composition of two ampules of a mixed bacterial influenza vaccine produced in 1916, which were labeled as containing killed Bacillus influenzae, Pneumococci, and Streptococcus pyogenes. Methods: DNA was extracted from two 1916-era vaccine ampules, and due to low DNA yields, whole genome amplification (WGA) was performed prior to construction of Illumina sequencing libraries. Deep sequencing was conducted, followed by bioinformatic analysis to identify bacterial DNA content. Consensus genomes were assembled for predominant species, and further analyzed for serotype, phylogeny, and antibiotic resistance genes. Results: The amount of recoverable DNA from these century-old vaccine ampules was limited. The sequencing results revealed minimal detectable S. pneumoniae DNA. The first ampule contained predominantly H. influenzae DNA, while the second vial primarily contained Enterococcus faecium DNA, in addition to S. pyogenes DNA. Consensus genomes for H. influenzae, S. pyogenes, and E. faecium were assembled and analyzed for serotype, phylogeny, and antibiotic resistance genes. Conclusions: This study presents the first genomic analysis of century-old bacterial pneumonia vaccine ampules from the 1918 influenza pandemic era. The findings provide a unique historical perspective on early vaccine formulations and highlight the limitations of early vaccine production. Full article

In developing countries like Bangladesh, livestock is one of the main sources of income. Among several infectious diseases, the Gram-positive bacterium Bacillus anthracis causes a zoonotic disease named anthrax. Animal anthrax outbreaks are a frequently occurring problem in Bangladesh. Our present study aims to molecularly identify and characterize B. anthracis from three districts of Bangladesh by 16S rRNA gene sequencing. B. anthracis was confirmed in soil, meat, and blood samples using PCR. Anthrax-affected soil (n = 128), blood (n = 1), and meat (n = 2) samples were analyzed using PCR. One of the positive samples was randomly chosen for sequencing, and MEGA5 software was used to generate the phylogenetic tree from the sequencing result. A total of 21 (16.40%) soil samples and all of the blood and meat samples were positive for the presence of bacteria, confirmed by PCR. The 16S rRNA gene of B. anthracis Sirajganj-1 was identical to that of other strains. To fulfill the Sustainable Development Goals, it is important to control zoonotic diseases. Our results may help discover the virulent genes of B. anthracis for future investigation and control this zoonotic disease. Also, a proper awareness of vaccination and effective surveillance system is important to eradicate any kind of zoonotic disease in developing nations. Full article

Sheep and goats are an important source of livelihood for smallholder farmers in sub-Saharan Africa (SSA). These livestock are almost entirely managed by resource-poor, smallholder farmers and pastoralists. Despite the large number of sheep and goats in SSA, their productivity is low, mainly due to diseases, poor feed, and inferior breeds. This review aims to summarize the most important diseases in small ruminants in SSA, with a focus on current treatment and control strategies. The following diseases were identified as the most significant constraints for small ruminant farmers: helminthoses, including gastrointestinal nematode infestation, lungworm infestation, fasciolosis, and cerebral coenurosis; viral diseases, such as peste des petits ruminants (PPR), sheep and goat pox, and contagious ecthyma (orf); bacterial diseases, including contagious caprine pleuropneumonia (CCPP), pneumonic pasteurellosis, and anthrax; as well as ectoparasite infestations. The diseases have significant economic implications due to mortality and production losses. Depending on the disease, they may also impact trade and export and hinder the introduction of new, more productive breeds. The ability to control diseases more efficiently is often limited due to financial constraints. In the case of infection with internal parasites, a lack of knowledge about the epidemiology of the disease, as well as the availability of appropriate anthelmintics and the development of resistance against commonly used anthelmintics, are often barriers. The control of viral diseases depends on the accessibility, quality, and handling of vaccines, whereas in bacterial diseases, increasing antibiotic resistance and inappropriate antimicrobial treatments pose challenges, as well as the availability of appropriate vaccines and their use. In the case of ectoparasitic infections, a strategic, regular, and appropriate antiparasitic treatment approach is often not achieved. Full article

Bacillus anthracis is a deadly pathogen that under unfavourable conditions forms highly resistant spores which enable them to survive for a long period of time. Spores of B. anthracis are transmitted through the contaminated soil or animal products and enter to the host through the skin, lungs or oral route and can cause cutaneous, injection, inhalation and gastrointestinal anthrax, respectively. The disease is caused by the toxin which is produced by them once they germinate within the host cell. Anthrax toxin is the major virulence factor which has the ability to kill the host cell. The role of protein kinases and phosphatases of B. anthracis in toxin production and other virulence related properties have also been reported. There are two vaccines, BioThrax and CYFENDUS^TM, which are approved by the FDA-USA to prevent anthrax disease. Recently, anthrax toxin has also been shown to be a potential candidate for cancer therapeutics. Through present review, we aim to provide insights into sporulation, transmission and pathogenesis of B. anthracis as well as the current state of its prevention, treatment, vaccines and possible therapeutic uses in cancer. Full article

Background: Anthrax is a serious disease caused by Bacillus anthracis (B. anthracis) with a very high mortality when the spores of B. anthracis are inhaled (inhalational anthrax). Aerosolized B. anthracis spores can be used as a deadly bioweapon. Vaccination against anthrax is the only effective preventive measure and, hence, the anthrax vaccine was administered to United States (and other) troops during the 1990–91 Gulf War. However, the anthrax vaccine is not harmless, and the anthrax vaccination has been linked to the occurrence and severity of Gulf War Illness (GWI), a debilitating Chronic Multisymptom Illness (CMI). We hypothesized that this is partly due to the combination of two factors, namely (a) the cytotoxicity of the antigen (anthrax Protective Antigen, PA) contained in the vaccine, and (b) the Human Leukocyte Antigen (HLA) genotype of susceptible vaccinees, reducing their ability to make antibodies against the cytotoxic PA. Method: Here, we tested this hypothesis by determining the association between severity of GWI symptoms in 458 GW veterans and the overall strength of the binding affinity of the PA epitopes to the specific six Human Leukocyte Antigen (HLA) Class II alleles carried by each individual (two of each of the HLA-II genes: DPB1, DQB1, DRB1), responsible for initiating the process of antibody production in otherwise immunocompetent individuals, estimated in silico. Results: We found that the severity of GWI symptomatology was negatively and significantly correlated with the strength of the predicted binding affinity of PA peptides to HLA-II molecules ($r=-0.356, p<0.001)$; the stronger the overall binding affinity, the weaker the symptoms. Since the binding of a peptide to an HLA-II molecule is the first and necessary step in initiating the production of antibodies, the findings above support our hypothesis that the severity of GWI symptomatology is partly due to a lack of HLA-II protection. Conclusions: Reduced HLA protection against the toxic anthrax vaccine may underlie GWI. Full article

The anthrax pathogen Bacillus anthracis can remain dormant as spores in soil for many years. This applies to both natural foci and to sites of anthropogenic activity such as tanneries, abattoirs, or wool factories. The A.Br.075 (A-branch) clade (also known as A.Br.Sterne) is prominent not only because it comprises several outbreak strains but even more so because spore preparations of its namesake, the Sterne strain, are counted among the most utilized anthrax animal vaccines. In this study, we genome-sequenced and analyzed 56 additional B. anthracis isolates of the A.Br.075 clade. Four of these we recently retrieved from soil samples taken from a decades-long abandoned tannery. The other 52 strains originated from our archival collection from the 20th century. Notably, the extended phylogeny of the A.Br.075 clade indicated that many of the newly added chromosomes represent basal members, some of which are among the most basal strains from this lineage. Twelve new strains populate a very deep-branching lineage we have named A.Br.Ortho-Sterne (also known as A.Br.076). A further 11 isolates amend the clade named A.Br.Para-Sterne (A.Br.078). Finally, some of the terminal clusters of the clade named A.Br.Eu-Sterne appear to be replete with (near) identical isolates, possibly a result of widespread use of the Sterne vaccine and of its re-isolation from vaccination-related animal anthrax outbreaks. From the accrued new phylogenetic information, we designed and tested a variety of new SNP-PCR assays for rapid and facile genotyping of unassigned B. anthracis genomes. Lastly, the successful isolation of live B. anthracis from a long-abandoned tannery reemphasizes the need for continued risk awareness of such sites. Full article

The COVID-19 and mpox crisis has reminded the world of the potentially catastrophic consequences of biological agents. Aside from the natural risk, biological agents can also be weaponized or used for bioterrorism. Dissemination in a population or among livestock could be used to destabilize a nation by creating a climate of terror, by negatively impacting the economy and undermining institutions. The Centers for Disease Control and Prevention (CDC) classify biological agents into three categories (A or Tier 1, B and C) according to the risk they pose to the public and national security. Category A or Tier 1 consists of the six pathogens with the highest risk to the population (Bacillus anthracis, Yersinia pestis, Francisella tularensis, botulinum neurotoxins, smallpox and viral hemorrhagic fevers). Several medical countermeasures, such as vaccines, antibodies and chemical drugs, have been developed to prevent or cure the diseases induced by these pathogens. This review presents an overview of the primary medical countermeasures, and in particular, of the antibodies available against the six pathogens on the CDC’s Tier 1 agents list, as well as against ricin. Full article

Anthrax, a zoonotic disease affecting both livestock and humans globally, is caused by Bacillus anthracis. The objectives of this study were the following: (1) to identify environmental risk factors for anthrax and use this information to develop an improved predictive risk map, and (2) to estimate spatial variation in basic reproduction number (Ro) and herd immunity threshold at the village level, which can be used to optimize vaccination policies within high-risk regions. Based on the anthrax incidences from 2000–2023 and vaccine administration figures between 2008 and 2022 in Karnataka, this study depicted spatiotemporal pattern analysis to derive a risk map employing machine learning algorithms and estimate Ro and herd immunity threshold for better vaccination coverage. Risk factors considered were key meteorological, remote sensing, soil, and geographical parameters. Spatial autocorrelation and SaTScan analysis revealed the presence of hotspots and clusters predominantly in the southern, central, and uppermost northern districts of Karnataka and temporal cluster distribution between June and September. Factors significantly associated with anthrax were air temperature, surface pressure, land surface temperature (LST), enhanced vegetation index (EVI), potential evapotranspiration (PET), soil temperature, soil moisture, pH, available potassium, sulphur, and boron, elevation, and proximity to waterbodies and waterways. Ensemble technique with random forest and classification tree models were used to improve the prediction accuracy of anthrax. High-risk areas are expected in villages in the southern, central, and extreme northern districts of Karnataka. The estimated Ro revealed 11 high-risk districts with Ro > 1.50 and respective herd immunity thresholds ranging from 11.24% to 55.47%, and the assessment of vaccination coverage at the 70%, 80%, and 90% vaccine efficacy levels, all serving for need-based strategic vaccine allocation. A comparison analysis of vaccinations administered and vaccination coverage estimated in this study is used to illustrate difference in the supply and vaccine force. The findings from the present study may support in planning preventive interventions, resource allocation, especially of vaccines, and other control strategies against anthrax across Karnataka, specifically focusing on predicted high-risk regions. Full article

We report on a highly significant, positive association between anthrax vaccination and occurrence of Gulf War Illness (GWI) in 111 Gulf War veterans (42 with GWI and 69 controls). GWI was diagnosed in 47.1% of vaccinated veterans but only in 17.2% of non-vaccinated veterans (Pearson χ² = 7.08, p = 0.008; odds ratio = 3.947; relative risk = 2.617), with 1.6x higher GWI symptom severity in vaccinated veterans (p = 0.007, F-test in analysis of covariance). Next, we tested the hypothesis that the susceptibility to GWI following anthrax vaccination could be due to inability to make antibodies against the anthrax protective antigen (PA), the key protein contained in the vaccine. Since the first step in initiating antibody production would be the binding of PA peptide fragments (typically 15-amino acid long [15-mer]) to peptide-binding motifs of human leukocyte antigen (HLA) Class II molecules, we assessed the binding-motif affinities of such HLA specific molecules to all linear 15-mer peptide fragments of the anthrax PA. We identified a total of 58 HLA Class II alleles carried by the veterans in our sample and found that, of those, 18 (31%) were present in the vaccinated group that did not develop GWI but were absent from the vaccinated group who developed GWI. Remarkably, in silico analyses revealed very high binding affinities of peptide-binding motifs of those 18 HLA alleles with fragments of anthrax vaccine PA, leading to the successful production of anti-PA antibodies. Conversely, the absence of these protective HLA alleles points to a reduced ability to develop antibodies against PA, thus resulting in harmful PA persistence and development of GWI. Full article

Vaccination against Bacillus anthracis 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). Full article

Institut Pasteur and Bacillus anthracis have enjoyed a relationship lasting almost 120 years, starting from its foundation and the pioneering work of Louis Pasteur in the nascent fields of microbiology and vaccination, and blooming after 1986 following the molecular biology/genetic revolution. This contribution will give a historical overview of these two research eras, taking advantage of the archives conserved at Institut Pasteur. The first era mainly focused on the production, characterisation, surveillance and improvement of veterinary anthrax vaccines; the concepts and technologies with which to reach a deep understanding of this research field were not yet available. The second period saw a new era of B. anthracis research at Institut Pasteur, with the anthrax laboratory developing a multi-disciplinary approach, ranging from structural analysis, biochemistry, genetic expression, and regulation to bacterial-host cell interactions, in vivo pathogenicity, and therapy development; this led to the comprehensive unravelling of many facets of this toxi-infection. B. anthracis may exemplify some general points on how science is performed in a given society at a given time and how a scientific research domain evolves. A striking illustration can be seen in the additive layers of regulations that were implemented from the beginning of the 21st century and their impact on B. anthracis research. B. anthracis and anthrax are complex systems that raise many valuable questions regarding basic research. One may hope that B. anthracis research will be re-initiated under favourable circumstances later at Institut Pasteur. Full article

Bacillus anthracis is a Gram-positive bacterium that causes the zoonotic disease anthrax. Here, we studied the characteristic phenotype and virulence attenuation of the putative No. II vaccine strain, PNO2, which was reportedly introduced from the Pasteur Institute in 1934. Characterization of the strain showed that, compared with the control strain, A16Q1, the attenuated PNO2 (PNO2D1) was phospholipase-positive, with impaired protein hydrolysis and significantly reduced sporulation. Additionally, PNO2D1 significantly extended the survival times of anthrax-challenged mice. An evolutionary tree analysis revealed that PNO2D1 was not a Pasteur strain but was more closely related to a Tsiankovskii strain. A database comparison revealed a seven-base insertion mutation in the nprR gene. Although it did not block nprR transcription, the insertion mutation resulted in the premature termination of protein translation. nprR deletion of A16Q1 resulted in a nonproteolytic phenotype that could not sporulate. The database comparison revealed that the abs gene is also prone to mutation, and the abs promoter activity was much lower in PNO2D1 than in A16Q1. Low abs expression may be an important reason for the decreased virulence of PNO2D1. Full article

Anthrax is one of the most important zoonotic diseases which primarily infects herbivores and occasionally humans. The etiological agent is Bacillus anthracis 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. Full article

The microbial pathogens Burkholderia pseudomallei and Bacillus anthracis are unrelated bacteria, yet both are the etiologic agents of naturally occurring diseases in animals and humans and are classified as Tier 1 potential biothreat agents. B. pseudomallei is the gram-negative bacterial agent of melioidosis, a major cause of sepsis and mortality globally in endemic tropical and subtropical regions. B. anthracis is the gram-positive spore-forming bacterium that causes anthrax. Infections acquired by inhalation of these pathogens are challenging to detect early while the prognosis is best; and they possess innate multiple antibiotic resistance or are amenable to engineered resistance. Previous studies showed that the early generation, rarely used aminocoumarin novobiocin was very effective in vitro against a range of highly disparate biothreat agents. The objective of the current research was to begin to characterize the therapeutic efficacy of novobiocin in mouse models of anthrax and melioidosis. The antibiotic was highly efficacious against infections by both pathogens, especially B. pseudomallei. Our results supported the concept that specific older generation antimicrobials can be effective countermeasures against infection by bacterial biothreat agents. Finally, novobiocin was shown to be a potential candidate for inclusion in a combined pre-exposure vaccination and post-exposure treatment strategy designed to target bacterial pathogens refractory to a single medical countermeasure. Full article

The causative agent of anthrax, Bacillus anthracis, evades the host immune response and establishes infection through the production of binary exotoxins composed of Protective Antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). The majority of vaccination strategies have focused upon the antibody response to the PA subunit. We have used a panel of humanised HLA class II transgenic mouse strains to define HLA-DR-restricted and HLA-DQ-restricted CD4+ T cell responses to the immunodominant epitopes of PA. This was correlated with the binding affinities of epitopes to HLA class II molecules, as well as the responses of two human cohorts: individuals vaccinated with the Anthrax Vaccine Precipitated (AVP) vaccine (which contains PA and trace amounts of LF), and patients recovering from cutaneous anthrax infections. The infected and vaccinated cohorts expressing different HLA types were found to make CD4+ T cell responses to multiple and diverse epitopes of PA. The effects of HLA polymorphism were explored using transgenic mouse lines, which demonstrated differential susceptibility, indicating that HLA-DR1 and HLA-DQ8 alleles conferred protective immunity relative to HLA-DR15, HLA-DR4 and HLA-DQ6. The HLA transgenics enabled a reductionist approach, allowing us to better define CD4+ T cell epitopes. Appreciating the effects of HLA polymorphism on the variability of responses to natural infection and vaccination is vital in planning protective strategies against anthrax. Full article