Synthetic Peptide Vaccine Targeting a Cryptic Neutralizing Epitope in Domain 2 of Bacillus anthracis Protective Antigen
Jon Oscherwitz,Jon Oscherwitz,Fen Yu,Jana L. Jacobs,Te Hui Liu,Philip R. Johnson,Kemp B. Cease,Kemp B. Cease +7 more
TLDR
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.read more
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The promise and challenge of epitope-focused vaccines.
TL;DR: Traditional vaccination with whole pathogens or pathogen-derived subunits has completely eliminated diseases like smallpox, and has greatly limited the incidence, morbidity and mortality associated with many other infectious diseases.
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Anthrax vaccines: present status and future prospects.
TL;DR: This work presents an overview of the current understanding of anthrax pathogenesis and recent advances made, particularly after 2001, for the successful management of Anthrax and outlines future perspectives.
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Protective Immunity against Trichinella spiralis Infection Induced by a Multi-Epitope Vaccine in a Murine Model
TL;DR: Results showed that a multi-epitope vaccine induced better protective immunity than an individual epitope and provided a feasible approach for developing a safer and more effective vaccine against trichinellosis.
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Identification and characterization of protective epitope of Trichinella spiralis paramyosin.
TL;DR: The identification of a protective epitope within Ts-Pmy highlights the possibility of developing a subunit vaccine against T. spiralis infection and a peptide based on this epitope region (YX1) was synthesized and shown to compete with native Ts- Pmy for binding to 7E2.
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A Synthetic Peptide Vaccine Directed against the 2β2–2β3 Loop of Domain 2 of Protective Antigen Protects Rabbits from Inhalation Anthrax
TL;DR: It is concluded that a synthetic peptide vaccine targeting the LND would be a potentially efficacious vaccine for anthrax.
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