2248. Potent and Sustained Activity of Novel THIOMAB™ Antibiotic Conjugate (TAC) against Staphylococcus aureus as Measured by Bioluminescence Imaging
Session: Poster Abstract Session: New Antibiotics in Development
Saturday, October 29, 2016
Room: Poster Hall
Background: Invasive Staphylococcus aureus (S. aureus) infections are the leading cause of death by an infectious agent. Bacterial survival within the host phagocytic cells is one potential mechanism by which S. aureus evades standard of care treatment. A novel THIOMAB™ antibiotic conjugate (TAC) strategy has been developed to target intracellular S. aureus (Figure 1). In this study, longitudinal whole body imaging was applied to monitor the progression of infection and the antibacterial dynamics of the TAC and vancomycin treatment in an intravenous (IV) mouse infection model.

Methods: An in vivo bioluminescence imaging method was established using stably luminescent S. aureus strain SAP149. SAP149 (1×107 CFU) was IV injected into SCID mice. At 24 hr post-infection, mice were given either: a single IV dose of TAC at 15, 50, or 100 mg/kg; repeated intraperitoneal (IP) doses of vancomycin at 110 mg/kg twice per day (BID) for 7 days; or repeated IP doses of saline control BID for 7 days. In vivo bioluminescence imaging was acquired with IVIS-Lumina-II to continuously monitor the total body bioluminescence intensity for 21 days post treatment.

Results: The imaging data (Figure 2) showed a rapid and significant reduction of the bioluminescence intensity after TAC treatment compared to the control group. In addition, the reduction of bioluminescence intensity was maintained for 7 to 21 days after a single dose of TAC, while bioluminescence intensity rebounded immediately after stopping vancomycin on day 7.

Conclusion: We have applied an imaging method to longitudinally assess the antibacterial dynamics of TAC and vancomycin treatment in vivo over a 3-week period. The imaging data demonstrated the superior and sustained antibacterial activity of TAC over vancomycin.

Chenguang Zhou, PhD1, Amos Baruch, PhD1, Saroja Ramanujan, PhD1, Thomas Pillow, PhD1, Meng Yang, PhD2, Fengxun Guo, MS2, Deming Xu, PhD2 and Amrita Kamath, PhD1, (1)Genentech, South San Francisco, CA, (2)WuXi AppTec (Shanghai) Co., Ltd. China, Shanghai, China

Disclosures:

C. Zhou, Genentech: Employee , Salary

A. Baruch, Genentech: Employee , Salary

S. Ramanujan, Genentech: Employee , Salary

T. Pillow, Genentech: Employee , Salary

M. Yang, None

F. Guo, None

D. Xu, None

A. Kamath, Genentech: Employee , Salary

Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.