Biodefense/Bioterrorism Therapeutic Countermeasures Laboratory


Henry HeineHenry Heine, Ph.D.
Associate Professor
College of Medicine
Department of Medicine

Faculty Profile

 

 

 

 

 

 

 

The primary objectives of the BBTC laboratory are to identify antibiotics and therapeutics to successfully treat patients exposed to agents of potential Bioterrorism/Biowarfare. This is accomplished by first testing direct exposure of potential new antibiotics to each organism directly, via susceptibility testing. Follow up studies involve treating mice infected with each organism to determine dose and timing of treatment. In addition to traditional antibiotic therapies, the laboratory also evaluates other therapies including immune-modulators alone or in combination with antibiotics. These studies open opportunities to further explore the various disease progressions and the interaction of the immune system in recovery or failure.

Under microscopeunder microscope

 

In addition to a fully equipped BSL3 facility, a key component and specialty of the laboratory is our Aerobiology core. The core has instrumentation and containment to deliver infectious aerosols to the animals in both the BSL3 and BSL2 facilities. This represents the expected route that individuals would be expected to be exposed with these infectious agents and allows evaluation of therapeutics in various inhalational and pneumonia infection models.

Of key importance is that the diseases caused by BT/BW infectious agents are usually rare and many lethal so classical clinical trials are impossible. Therefore, the regulatory process must make use of the FDA-“Animal rule”. The BBTC laboratory works with the Pharmaceutical Industry, DOD, CDC NIH, BARDA and the FDA to support approval and/or indication labeling of therapeutics through the regulatory process under the animal rule.

 

lab


Funding (2011-2019)

Current Projects

Agency Grant Title Dates Total Award
CTSI The Development and Use of a Murine Aerosol Challenge Model for Influenza Infection to Optimize Anti-Influenza Therapeutic Regimens.

 

Aug/2017Aug/2019 $25,000
Venatorx Pharm Penicillin Binding Proteins Jan/2019 $83,020
Spero Pharm In vitro biological evaluation of polymyxin analogs vesus category A and B pathogens. Aug/2018

Aug/2019

         $174,255
Wockhardt Bio Ag MIC90 determination of 2 β-lactam enhancer based antibacterial combinations from Nov/2017Dec/2017            $78,058
Achaogen, Inc. WITI Antibiotic Susceptibility Determinations Mar/2017-Jun/2017 $29,989
Emergent Biosolutions

DTRA

Tasks 2.1,2.2, 2.3 In Vivo Efficacy Study for Evaluation of the improved GC-072 formulation Mar/2017-Feb/18 $1,264,194
Us Army Med Res Acquisition In Vitro Antibiotic Therapeutic Services in Support of protocol #AP-10-047G:  Pharmokinetic and pharacodynamic analyses of intravenous Moxifloxican in Non-Human Primates using appropriate computer programs. (00084689) Jul/2012 –Jul/2017 $86,000
Emergent Biosolutions Task 2.5 In Vivo Efficacy Study to Identify Most Effective Doses (00098929) Sep/2014- Dec/2016 $142,100
Glaxo Smithkline Evaluation of the potential of  GSK2140944 in the vivo murine
inhalational models for Yersinia pestis:   Study #1 (00085366)
Apr/2012 – Apr/2016 $ 1,716,872
Cubric/Tetraphase Dose fractionation of TP-271 dosed intraperitoneally in an aerosolized Y. pestis mouse model (00096626) Feb/2015- Dec/2015 $   401,389
Glaxo Smithkline GSK BARDA Evaluation of GSK2251052; GSK awarded contract #HHS0100201100116C (00083452) Nov 2011 – Nov 2015 $   833,846
Battelle Memorial Inst DEVELOPMENT OF A MEROPENEM RESISTANT SA-5 MODEL IN BALB/C MICE, SUBTASK 1.1 SELECTION OF MEROPENEM RESISTANT SA-5… (00097198) Jan/2015 – Nov/2015 $   236,745
Ctrs For Disease Control & Prevention Evaluation of synergistic activity and efficacy of combination drug therapy for early treatment of multiple-resistant inhalation anthrax in the murine model. (00083097) Sep/2011 – Oct/2015 $   246,389
Cempra Pharmaceuticals Inc Determination of the in vitro solithromycin MIC/MBCs and Time-Kill kinetics against B. anthracis and F. tularensis strains (00096270) Dec/2014 – May/

2015

$    76,313
Actelion Pharmaceuticals Ltd MIC determination of 15 antibacterial compounds from Actelion against type strains of XXX (00092113) Feb/2014 – Jan/2015 $    75,792
Wockhardt Bio Ag Wockhardt Antibiotic Susceptibilities- Initial Screen (00092350) Feb/2014 – Jan/2015 $    18,530

 

Submitted – Pending Decision

Agency Grant Title Dates Total Award
DTRA Development of CZ-02s (AIIPS), a new class of antibacterial for the treatment of drug resistant bacterial infections, including those caused by multi-drug resistant Yersinia pestis, Franciisella tularensis, and Burkholderia mallei. 7/2019-12/2027 $75,081,291.00
NIH Elucidation of fluoroquinolone immunomodulation pneumonic Yersinia pestis infection in a murine model Fall/2019-/2024 $3,750.000

 

Submitted/not funded

 Proposed Role Agency Date of Submission Amount of Proposal
co-PI CERSI/NIAID 2016 $ 1,363,356.00
PI Cubist (MICs) 2015 $      64,599.00
PI Venatorx RO1/subcontract 2015 $    974,032.00
PI RibX/DTRA subcontract 2015 $    741,411.00
co-PI RO1 w/ Dr. Mohamadzadeh 2015 $    825,294.00
PI RibX/DTRA subcontract 2015 $    741,411.00
PI Echelon/RO1/NIAID 2015 $ 1,181,525.00
co-PI Eritoran/RO1/NIAID 2015 $    886,799.00
PI Allecra contract 2014 $      72,452.00
PI AlbanyMed/DTRA Subcontract 2014 $    669,990.00
PI Medicine Company 2014 $    184,434.00
PI Theravance/NIAID Subcontract 2014 $ 1,222,114.00

 


Publications

Book Chapters

Arthur M. Friedlander, and Henry Heine.  2016. Antimicrobial Therapy and Vaccines Volume I: Microbes  Third Edition. Bacillus anthracis (Anthrax).  Apple Trees Productions, LLC.  New York, New York.  67-72.

George L. Drusano, Henry Heine, and Arnold Louie.  2014. Fundamentals of Antimicrobials Pharmacokinetics and Pharmacodynamics. Clinical Pharmacodynamics of Quinolones.  Springer.  New York.  323-349.

 

Journal manuscripts

Heine HS, Shadomy SV, Boyer AE, Chuvala L, Riggins R, Kesterson A, Myrick J, Craig J, Candela MG, Barr JR, Hendricks K, Bower WA, Walke H, Drusano GL. 2017. Evaluation of combination drug therapy for treatment of antibiotic-resistant inhalation anthrax in a murine model. Antimicrob Agents Chemother 61:e00788-17.

Heine HS, Miller L, Halasohoris S, Purcell BK. 2017. In vitro antibiotic susceptibilities of Francisella tularensis determined by broth microdilution following CLSI methods. Antimicrob Agents Chemother 61:e00612-17.

Grossman TH, Anderson MS, Drabek L, Gooldy M, Heine HS, Henning LN, Lin W,

Newman JV, Nevarez R, Siefkas-Patterson K, Radcliff AK, Sutcliffe JA. 2017. The Fluorocycline TP-271 is efficacious in models of aerosolized Bacillus anthracis infection in BALB/c mice and cynomolgus macaques. Antimicrob Agents Chemother 61:e01103-17.

Grossman TH, Anderson MS, Christ D,Gooldy M, Henning LN, Heine HS, Kindt MV, Lin W, Siefkas-Patterson K, Radcliff AK, Tam VH,Sutcliffe JA. 2017. The fluorocycline TP-271 is efficacious in models of aerosolized Francisella tularensis SCHU S4 infection in BALB/c mice and cynomolgus macaques. Antimicrob Agents Chemother 61:e00448-17.

Heine, HS, Chuvala, L, Riggins, R, Cirz, R, Cass, R, Louie, A, and Drusano, GL.  2016. Natural History of Francisella tularensis in Aerosol-Challenged BALB/c Mice.  Antimicrobial Agents and Chemotherapy.  60(3): 1834-1840.

Heine, HS, Hershfield, J, Marchand, C, Miller, L, Halasohoris, S, Purcell, BK, and Worsham, P.  2015. In Vitro Antibiotic Susceptibilities of Yersinia pestis Determined by Broth Microdilution following CLSI Methods.  Antimicrobial Agents and Chemotherapy.  59(4): 1919-1921.

Heine, HS, Louie A, Adamovicz, J, Amemiya, K, Fast, R, Miller, L, Opal, S, Palardy, J, Parajo, N, Sorgel, F, Kinzig-Schippers, M, and Drusano, GL.  2014. Evaluation of Imipenem for Prophylaxis and Therapy of Yersinia pestis Delivered by Aersol in a Mouse Model of Pneumonic Plague.  Antimicrobial Agents and Chemotherapy.  58(6): 3276-3284.

Heine HS, Chuvala L, Riggins R, Hurteau G, Cirz R, Cass R, Louie A, and Drusano GL(&).  2013. Natural history of Yersinia pestis pneumonia in aerosol-challenged BALB/c mice.  Antimicrob. Agents Chemother.  57(5): 2010-5.

Louie A, VanScoy BD, Brown DL, Kulawy RW, Heine HS, and Drusano GL.  2012. Impact of spores on the comparative efficacies of five antibiotics for treatment of Bacillus anthracis in an in vitro hollow fiber pharmacodynamic model.  Antimicrob. Agents Chemother.  56(3): 1229-39.

Louie A, VanScoy BD, Heine HS 3rd, Liu W, Abshire T, Holman K, Kulawy R, Brown DL, and Drusano GL.  2012. Differential effects of linezolid and ciprofloxacin on toxin production by Bacillus anthracis in an in vitro pharmacodynamic system.  Antimicrob. Agents Chemother.  56(1): 513-7.

Louie A, Heine HS, VanScoy B, Eichas A, Files K, Brown DL, Liu W, Kinzig-Schippers M, Sorgel F, and Drusano GL.  2011. Use of an in vitro pharmacodynamic model to derive a moxifloxacin regimen that optimizes kill of Yersinia pestis and prevents emergence of resistance.  Antimocrob. Agents Chemother.  55(2): 822-30.

 

Abstracts, Posters

H.S. Heine, S.V. Shadomy(&), A.E. Boyer(&), L. Chuvala(&), R. Riggins(&), J. Myrick(&), J. Craig(&), G.L.Drusano(&), M.G. Candela(&), J.R. Barr(&), K. Hensricks(&), W.A. Bower(&), and H. Walke(&). Poster. Evaluation of Synergistic Activities & Efficacy of Combination Drug Therapy for Antibiotic Resistant Inhalation Anthrax in a Murine Model. American Society for Microbiology Microbe. Boston, Massachusetts. Jun 16, 2016 – Jun 20, 2016.

H.S. Heine, S.T. Demons(&), L.L. Miller(&), S.A. Halasohoris(&), J. Myrick(&), L. Morris(&), and L. Chuvala(&). Poster. In vitro Activity of WCK771, a Broad Spectrum Anti-MRSA Benzoquinolizine subclass of Quinolone Against five Biodefense Bacterial Pathogens. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). San Diego, California. Sep 17, 2015 – Sep 21, 2015.

H.S. Heine, L. Chuvala(&), R. Riggins(&), J. Myrick(&), L. Morris(&), and G.D. Drusano(&). Poster. Application of Pharmacokinetics/Pharmacodynamics to Development of Fluoroquinolone Therapy to Treat Bacterial Biothreat Infections. American Society for Microbiology. New Orleans, Louisianna. Jun 1, 2015 – Jun 1, 2015.

H.S. Heine, L. Chuvala(&), R. Riggins(&), C. Jakielaszek(&), S. Novick(&), J. Hoover(&), and G. Feuerstein(&). Poster. Determination of the Ld50 and Ld90 for Aerosolized Francisella tularensis (FT) Schus4 in Mice and Identification of Factors to Control Aerosol Variability. ASM Biodefense and Emerging Diseases Research Meeting. Washington, DC. Feb 9, 2015 – Feb 11, 2015.

S.A. Orr(&), D.K. O’Brien(&), J. C. Waldrep(&), M. L. Saylor(&), H. S. Heine, G. L. Drusano(&), R. L. DaSilva(&), N. J. Vietri(&), P. M. Silvera(&), and B. K. Purcell(&). Poster. A Pharmacokinetic Comparison of Intravenous Moxifloxacin in Cynomolgus Macaque and African Green Monkeys Using Monte Carlo Simulations to Support Animal Rule Efficacy Studies. ASM Biodefense and Emerging Diseases Research Meeting. Washington, DC. Jan 27, 2014 – Jan 29, 2014.

H.S. Heine, L. Chuvala(&), R. Riggins(&), M. Gwynn(&), C. Jakielaszek(&), K. Widdowson(&), L. Miller(&), S. Halasohoris(&), J. Hershfield(&), and G. Feuerstein(&). Poster. In Vitro Activity and Efficacy in a Murine-Aerosol Challenge Model of a Novel Antibacterial GSK2140944 against Yersinia pestis. ASM Biodefense and Emerging Diseases Research Meeting. Washington, DC. Jan 27, 2014 – Jan 29, 2014.

C. Marchand(&), H.S. Heine, L. Miller(&), S. Halasohoris(&), J. Hershfield(&), A. Serio(&), and R. Cirz(&). Poster. In Vitro Activity of ACHN-975 Against Biodefense Pathogens. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Denver, Colorado. Sep 10, 2013 – Sep 13, 2013.

H.S. Heine, L. Chuvala, R.Riggins(&), and R. Cirz(&). Poster. Efficacy of ACHN-975 in a Murine Pneumonic Plague (Yersinia pestis) Model. Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Denver, Colorado. Sep 10, 2013 – Sep 13, 2013.