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Principal Investigator: Karl E Klose
Organization: UNIVERSITY OF TEXAS SAN ANTONIO
Fiscal Year: 2019
Award: $223,250
Funding agency: National Institute of Allergy and Infectious Diseases
Francisella tularensis (Ft), Yersinia pestis (Yp), and Bacillus anthracis (Ba) are considered Category A
bioweapons due to ease of transmission, low infectious dose and high mortality associated with pneumonic
forms of disease, and the fact that all have been intensively studied and developed in bioweapons programs in
several countries. There are currently no vaccines against tularemia or plague approved for general human
use, rendering mankind at significant risk from the illicit use of Ft and Yp. Our prior studies have shown that a
Ft subsp. novicida (Fn) FPI mutant (Fn-iglD) can protect against a pulmonary challenge of Ft subsp. tularensis
(Ftt), in both rat and non-human primate (NHP) models of tularemia. This is an extremely promising result,
because Fn is naturally avirulent toward humans, and thus a safer basis for a human vaccine. Antibodies
against the Yp F1 capsular and LcrV virulence antigens fused into a single polypeptide (F1V) have been
shown to be protective against Yp pulmonary challenge in several animal models, including NHP. Moreover,
antibodies against the Ba protective antigen (PA) protect against Ba pulmonary challenge. The studies
outlined here are designed to optimize the Fn-iglD vaccine platform to provide protection against Yp and Ba by
expression of F1V and PA. The Fn-iglD vaccine strain will be engineered to present F1V on its surface and to
secrete PA. The efficacy of this vaccine to protect against pulmonary challenge with Ftt and/or Yp, as well as
challenge with anthrax lethal toxin (LT) will be measured in the rat model. The result of these studies will be a
vaccine with broad efficacy against multiple biothreat agents. The collaborative team at UTSA and UTHSCSA
has extensive experience in tularemia, plague, and anthrax vaccine development that will propel the further
development of this biothreat vaccine platform. The R21 mechanism is intended to fund “early and conceptual
stages of project development”; upon completion of the experiments outlined in this proposal, this project will
be poised for the submission of a well-developed RO1 proposal directed at an effective multivalent biodefense
vaccine.
Terms: <ATGN><Animal Model><Animal Models and Related Studies><Animals><Anthrax><Anthrax Vaccines><Anthrax disease><Antibodies><Antibody titer measurement><Antigens><Attenuated Vaccines><B anthracis><B anthracis LeTx><B anthracis LeTx toxin><B. anthracis><Bacillus anthracis><Bacillus anthracis LF protein><Bacillus anthracis PA antigen><Bacillus anthracis anthrax toxins translocating protein><Bacillus anthracis lef protein><Bacillus anthracis lethal toxin><Bacillus anthracis pag protein><Bacillus anthracis pagA protein><Categories><Chimera Protein><Chimeric Proteins><Common Rat Strains><Country><Development><Disease><Disorder><Dose><Engineering><Exhibits><Exploratory/Developmental Grant><F tularensis><F. tularensis><Foundations><Francisella infection><Francisella tularensis><Francisella tularensis infection><Funding><Fusion Protein><Goals><H-D Antigens><Hanganutziu-Deicher Antigens><Health><Heteroantigens><Heterogenetic Antigens><Heterologous Antigens><Heterophil Antigens><Heterophile Antigens><Human><Immune response><Immunity><Immunological response><LeTx><Lung><Lung Respiratory System><Measures><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Modeling><Modern Man><Pasteurella pestis><Pasteurella tularensis><Paul-Bunnell Antigens><Plague><Plague Vaccine><Protein Engineering><R21 Mechanism><R21 Program><Rat><Rats Mammals><Rattus><Research><Risk><Route><Surface><Surface Proteins><System><Transmission><Tularemia><Vaccinated><Vaccines><Virulence><Xenoantigens><Xenogeneic Antigens><Xenogenic Antigens><Y pestis><Y. pestis><Y.pestis><Yersinia pestis><Yersinia pestis disease><anthracis><anthrax lethal factor><anthrax lethal toxin><anthrax protective antigen><anthrax protective factor><anthrax toxin LF><anthrax toxin PA><antibody titering><bio-threat><biodefense><biological weapon><biothreat><bioweapon><design><designing><develop a vaccine><development of a vaccine><developmental><experience><experiment><experimental research><experimental study><exploratory developmental study><genetic protein engineering><host response><immunogen><immunogenicity><immunoresponse><lethal factor><lethal toxin><live vaccine><model of animal><model organism><mortality><mutant><non-human primate><nonhuman primate><polypeptide><programs><protective antigen Bacillus anthracis><protective efficacy><protein design><pulmonary><synergism><transmission process><vaccine delivery><vaccine development><vaccine efficacy><vaccine formulation>