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Anthrax vaccines
About: Anthrax vaccines is a research topic. Over the lifetime, 685 publications have been published within this topic receiving 21495 citations.
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TL;DR: Analysis of sera from multiple cohorts of rabbits with high-titer immunity to PA demonstrated a virtual absence of this potent antibody specificity, and work by others suggests that this specificity may be present at only low levels in primate PA antiserum.
Abstract: Current evidence suggests that protective antigen (PA)-based anthrax vaccines may elicit a narrow neutralizing antibody repertoire, and this may represent a vulnerability with PA-based vaccines. In an effort to identify neutralizing specificities which may complement those prevalent in PA antiserum, we evaluated whether sequences within the 2β2-2β3 loop of PA, which are apparent in the crystal structure of heptameric but not monomeric PA, might represent a target for an epitope-specific vaccine for anthrax and, further, whether antibodies to these sequences are induced in rabbits immunized with monomeric PA. We evaluated the immunogenicity in rabbits of a multiple antigenic peptide (MAP) displaying copies of amino acids (aa) 305 to 319 of this region. Overall, four out of six rabbits vaccinated with the MAP peptide in Freund's adjuvant developed high-titer, high-avidity antibody responses which cross-reacted with the immobilized peptide sequence comprising aa 305 to 319 and with PA, as determined by an enzyme-linked immunosorbent assay, and which displayed potent and durable neutralization of lethal toxin (LeTx) in vitro, with peak titers which were 452%, 100%, 67%, and 41% of the peak neutralization titers observed in positive-control rabbits immunized with PA. Importantly, analysis of sera from multiple cohorts of rabbits with high-titer immunity to PA demonstrated a virtual absence of this potent antibody specificity, and work by others suggests that this specificity may be present at only low levels in primate PA antiserum. These results highlight the potential importance of this immunologically cryptic neutralizing epitope from PA as a target for alternative and adjunctive vaccines for anthrax.
31 citations
TL;DR: Comparison of 1998 hospitalizations in active-duty US military personnel for possible temporal association with anthrax immunization suggests that immunized service members were at equal or lesser risk for hospitalization than the non-immunized.
31 citations
TL;DR: Several attenuated strains expressing lethal toxin components PA and LF, which are biologically inactive, yet retain their antigenic properties could be an effective alternatives to their native counterparts when presented to the immune system in context of a live B. anthracis strain.
31 citations
TL;DR: It is demonstrated that antibiotic treatment can prevent the development of fatal disease in respiratory-anthrax-infected animals and can cure animals after disease establishment.
Abstract: Respiratory anthrax, in the absence of early antibiotic treatment, is a fatal disease. This study aimed to test the efficiency of antibiotic therapy in curing infected animals and those sick with anthrax. Postexposure prophylaxis (24 h postinfection [p.i.]) of guinea pigs infected intranasally with Bacillus anthracis Vollum spores with doxycycline, ofloxacin, imipenem, and gentamicin conferred protection. However, upon termination of treatment, the animals died from respiratory anthrax. Combined treatment with antibiotics and active vaccination with a protective antigen-based vaccine leads to full protection even after cessation of treatment. Delaying the initiation of antibiotic administration to over 24 h p.i. resulted in treatment of animals with anthrax exhibiting various degrees of bacteremia and toxemia. Treatment with doxycycline or ciprofloxacin cured sick guinea pigs and rabbits exhibiting bacteremia levels up to 10(5) CFU/ml. Addition of anti-protective antigen (PA) antibodies augmented the efficiency of protection, allowing the cure of guinea pigs and rabbits with 10- to 20-fold-higher bacteremia levels, up to 7 × 10(5) CFU/ml and 2 × 10(6) CFU/ml, respectively. Treatment with ciprofloxacin and a monoclonal anti-PA antibody rescued rabbits with bacteremia levels up to 4 × 10(6) CFU/ml. During antibiotic administration, all surviving animals developed a protective immune response against development of a fatal disease and subcutaneous challenge with Vollum spores. In conclusion, these results demonstrate that antibiotic treatment can prevent the development of fatal disease in respiratory-anthrax-infected animals and can cure animals after disease establishment. A therapeutic time window of 40 h to 48 h from infection to initiation of efficient antibiotic-mediated cure was observed.
31 citations
TL;DR: Seven groups were vaccinated with a human live anthrax vaccine by three different routes (scarification, subcutaneous and aerosol) and the kinetic pattern obtained from all groups, shows a significant, five-phased curve.
31 citations