Being Prepared

Weant, Kyle A.; Bailey, Abby M.; Fleishaker, Elise L.; Justice, Stephanie Baker

doi:10.1097/tme.0000000000000034

Cited by 3 publications

(1 citation statement)

References 18 publications

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“…BoNT subtypes are responsible for causing the serious paralytic disease botulism and their potent neuroparalytic activities make them one of the top (tier 1) agents considered to pose a significant threat to public health if used for bioterrorism (Electronic Code of Federal Regulations-Title 42: Part 73; http://www.ecfr.gov/cgi -bin/retrieveECFR?rϭPART&nϭ42y1.0.1.6.61) (9,10). The same properties also make them powerful tools for both medical therapeutic and cosmetic applications (11).…”

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confidence: 99%

Genomic Epidemiology of Clostridium botulinum Isolates from Temporally Related Cases of Infant Botulism in New South Wales, Australia

et al. 2015

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dInfant botulism is a potentially life-threatening paralytic disease that can be associated with prolonged morbidity if not rapidly diagnosed and treated. Four infants were diagnosed and treated for infant botulism in NSW, Australia, between May 2011 and August 2013. Despite the temporal relationship between the cases, there was no close geographical clustering or other epidemiological links. Clostridium botulinum isolates, three of which produced botulism neurotoxin serotype A (BoNT/A) and one BoNT serotype B (BoNT/B), were characterized using whole-genome sequencing (WGS). In silico multilocus sequence typing (MLST) found that two of the BoNT/A-producing isolates shared an identical novel sequence type, ST84. The other two isolates were single-locus variants of this sequence type (ST85 and ST86). All BoNT/A-producing isolates contained the same chromosomally integrated BoNT/A2 neurotoxin gene cluster. The BoNT/B-producing isolate carried a single plasmid-borne bont/B gene cluster, encoding BoNT subtype B6. Single nucleotide polymorphism (SNP)-based typing results corresponded well with MLST; however, the extra resolution provided by the whole-genome SNP comparisons showed that the isolates differed from each other by >3,500 SNPs. WGS analyses indicated that the four infant botulism cases were caused by genomically distinct strains of C. botulinum that were unlikely to have originated from a common environmental source. The isolates did, however, cluster together, compared with international isolates, suggesting that C. botulinum from environmental reservoirs throughout NSW have descended from a common ancestor. Analyses showed that the high resolution of WGS provided important phylogenetic information that would not be captured by standard seven-loci MLST. Genomic epidemiology has provided novel insights into the genetic characteristics and phylogenetic diversity of botulinum neurotoxin (BoNT)-producing Clostridium species (1-8).BoNT subtypes are responsible for causing the serious paralytic disease botulism and their potent neuroparalytic activities make them one of the top (tier 1) agents considered to pose a significant threat to public health if used for bioterrorism (Electronic Code of Federal Regulations-Title 42: Part 73; http://www.ecfr.gov/cgi -bin/retrieveECFR?rϭPART&nϭ42y1.0.1.6.61) (9, 10). The same properties also make them powerful tools for both medical therapeutic and cosmetic applications (11).Botulism is a very rare disease in Australia (National Notifiable Diseases Surveillance System [NNDSS]; http://www9.health.gov .au/cda/source/cda-index.cfm), with only 20 cases reported since 1991. However, a global survey found that Australia had one of the highest numbers of notified cases of infant botulism in the world (12, 13). Infant botulism results from the ingestion of Clostridium botulinum spores which germinate and temporarily colonize the infant's colon, followed by growth of vegetative cells that produce . This form of the disease only occurs in infants, generally under 1 year old, as they h...

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Genomic Epidemiology of Clostridium botulinum Isolates from Temporally Related Cases of Infant Botulism in New South Wales, Australia

et al. 2015

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Bioterrorism

Ferreira

Doursout²,

Balingit³

2023

2000 Years of Pandemics

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Identification of protective T-cell antigens for smallpox vaccines

et al. 2020

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Background aims: E3L is an immediate-early protein of vaccinia virus (VV) that is detected within 0.5 h of infection, potentially before the many immune evasion genes of vaccinia can exert their protective effects. E3L is highly conserved among orthopoxviruses and hence could provide important protective T-cell epitopes that should be retained in any subunit or attenuated vaccine. We have therefore evaluated the immunogenicity of E3L in healthy VV-vaccinated donors. Methods: Peripheral blood mononuclear cells from healthy volunteers (n = 13) who had previously received a smallpox vaccine (Dryvax) were activated and expanded using overlapping E3L peptides and their function, specificity and antiviral activity was analyzed. E3L-specific T cells were expanded from 7 of 12 (58.3%) vaccinated healthy donors. Twenty-five percent of these produced CD8+ T-cell responses and 87.5% produced CD4+ T cells. We identified epitopes restricted by HLA-B35 and HLA-DR15. Results: E3L-specific T cells killed peptide-loaded target cells as well as vaccinia-infected cells, but only CD8+ T cells could prevent the spread of infectious virus in virus inhibition assays. The epitopes recognized by E3Lspecific T cells were shared with monkeypox, and although there was a single amino acid change in the variola epitope homolog, it was recognized by vaccinia-specific T-cells. Conclusions: It might be important to include E3L in any deletion mutant or subunit vaccine and E3L could provide a useful antigen to monitor protective immunity in humans.

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Being Prepared

Cited by 3 publications

References 18 publications

Genomic Epidemiology of Clostridium botulinum Isolates from Temporally Related Cases of Infant Botulism in New South Wales, Australia

Genomic Epidemiology of Clostridium botulinum Isolates from Temporally Related Cases of Infant Botulism in New South Wales, Australia

Bioterrorism

Identification of protective T-cell antigens for smallpox vaccines

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