Affiliation:
1. Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts 02114
2. Department of Medicine
3. Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115
Abstract
ABSTRACT
We
identified spore targets of Anthrax Vaccine Adsorbed (AVA)-induced
immunity in humans by screening recombinant clones of a previously
generated, limited genomic
Bacillus anthracis
Sterne
(pXO1
+
, pXO2
−
) expression library
of putative spore surface (spore-associated [SA]) proteins with pooled
sera from human adults immunized with AVA (immune sera), the anthrax
vaccine currently approved for use by humans in the United States. We
identified 69 clones that reacted specifically with pooled immune sera
but not with pooled sera obtained from the same individuals prior to
immunization. Positive clones expressed proteins previously identified
as localized on the anthrax spore surface, proteins highly expressed
during spore germination, orthologs of proteins of diverse pathogens
under investigation as drug targets, and orthologs of proteins
contributing to the virulence of both gram-positive and gram-negative
pathogens. Among the reactive clones identified by this immunological
screen was one expressing a 15.2-kDa hypothetical protein encoded by a
gene with no significant homology to sequences contained in databases.
Further studies are required to define the subset of SA proteins
identified in this study that contribute to the virulence of this
pathogen. We hypothesize that optimal delivery of a subset of SA
proteins identified by such studies to the immune system in combination
with protective antigen (PA), the principal immunogen in AVA, might
facilitate the development of defined, nonreactogenic, more-efficacious
PA-based anthrax vaccines. Future studies might also facilitate the
identification of SA proteins with potential to serve as targets for
drug design, spore inactivation, or spore detection
strategies.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
31 articles.
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