Facilitated By

San Antonio Medical Foundation

Advanced Development of Vaccines Against F. tularensis, a Category A Select Agent

The University of Texas at San Antonio

The University of Texas at San Antonio is an emerging Tier One research institution with nearly 29,000 students.

Principal Investigator(s)
Klose, Karl
Hung, Chiung-Yu
Arulanandam, Bernard
Yu, Jieh-Juen
Funded by
Southwest Res Inst
Research Start Date
Status
Active

Francisella tularensis is considered a Category A bioweapon due to the ease of transmission, the low infectious dose and high mortality associated with the pneumonic form of disease, and the fact that these bacteria have been intensively studied and developed in bioweapons programs in several countries.  There are currently no vaccines approved for general human use, rendering mankind at significant risk from the illicit use of F. tularensis. Our prior studies have identified a novel vaccine platform that consists of a live attenuated strain created from F. novicida (Fn-iglD).  Fn-iglD vaccination protects against pulmonary challenge with Type A F. tularensis Schu S4 in both Fischer 344 rats and non-human primates (NHP; cynomolgus macaques).   We have further modified this strain to express the OAg from FTT (Fn-iglD OAgFTT), which is known to contribute to the induction of protective antibodies.  The Fn-iglD OAgFTT  strain (KKF768)thus represents an advanced tularemia vaccine candidate that requires refinement in order to optimize protection and proceed to translational vaccine development. The studies outlined here are designed to optimize the KKF768 vaccine platform to enhance immunogenicity and efficacy against F. tularensis. We propose to improve the KKF768 vaccine platform by encapsulation to (1) provide vaccine stability and tolerance to extreme pH environment (stomach) and (2) extend priming period by slow release of vaccine strain from biodegradable particles for enhacing duration of immunity. We will utilize both oral and microneedle array intradermal routes of vaccination. The intradermal vaccination can develop long term immunity suitable for military personnel deployed in combat zones, while oral vaccination has the advantage of rapid and massive administration without trained medical staff critical in the event of a terrorist attack involving the release of aerosolized F. tularensis. We will first screen vaccine formulations in the mouse model to select lead candidates that induce long term humoral and cell-mediated immunity. The down-selected vaccine candidates will then be evaluated in the Fischer 344 rats for their protective efficacy against pulmonary F. tularensis (SCHU S4) challenge, immune correlates and protective immune components/mechanisms. The most effective vaccine formulation(s) will then be tested in cynomolgus macaques for protective efficacy against pulmonary F. tularensis (SCHU S4) challenge. Finally, the enhanced KKF768 vaccine will then be formulated under cGMP guidelines.  Data obtained from proposed tasks will be packaged for IND submission.

Collaborative Project
Basic Research
Infectious Disease