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Development and Field Testing of a Novel Reservoir Targeted Antibiotic Against Borrelia burgdorferi

Award Number: R01AI152210
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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The incidence and geographic distribution of Lyme disease in the U.S. has increased steadily since its first description in 1977. Efforts to stem the spread of the disease through controlling the population of its tick vector and/or the mouse reservoirs of the disease have met with only limited success. The only approved human vaccine to protect against Lyme disease was removed from the market by its manufacturer further highlighting the need for new approaches to controlling the disease. In this project, we propose the development of a novel antibiotic targeted towards the mouse and tick reservoirs of the disease. This proposal combines the expertise in drug development of Dr. Kim Lewis’ laboratory, the expertise in Borrelia burgdorferi biology in Dr. Linden Hu’s laboratory and the field expertise of Dr. Sam Telford’s laboratory. Treatment of mice with an antibiotic, doxycycline, has been shown to be highly effective in eradicating Borrelia burgdorferi from its reservoir hosts. However, there is legitimate concern for development of resistance, both in B. burgdorferi and in other organisms that may be exposed to the antibiotic should it be widely distributed. Doxycyline is an important antibiotic in the treatment of multiple different human infections and in some cases such as Anaplasma or Rocky Mountain Spotted Fever, the only approved agent available. We have identified an antibiotic, hygromycin A (HygA), that is highly active against B. burgdorferi but has limited activity against other human pathogens. Its mechanism of action is different from other human antibiotics. In our preliminary data, we have shown that it is very effective in clearing B. burgdorferi from infected mice when given orally by gavage or in bait formulations. In this proposal, we will complete the steps in developing HygA as an environmental antibiotic and perform a limited field trial on an isolated island off the coast of MA to test its ability to control infection rates in ticks and mice. In Aim 1, we will establish the pharmacodynamics, stability and safety profile of HygA in Peromyscus mice. We will determine optimum concentrations for bait distribution and perform simulation studies of bait uptake and clearance in caged animals. In Aim 2, we will attempt to induce resistance to HygA in B. burgdorferi and in other organisms of human importance that are likely to encounter HygA in the environment. We will confirm that if HygA resistance develops, it does not cause concomitant resistance to other antibiotics with human applications. Finally, in Aim 3, we will perform a limited field trial on an isolated island that is endemic for B. burgdorferi in ticks and mice to establish the efficacy of a HygA based reservoir targeted antibiotic approach. This study has the potential to have a major impact on human Lyme disease by controlling the organism in its major reservoirs. By utilizing an antibiotic that has a narrow spectrum of activity and does not have human applications, we hope to replicate the success seen with doxycycline, which is arguably the most successful trial of any environmental approach to eradication to date, without the attendant concerns for resistance.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $348,435 )
2024	2024	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	5	6/14/2024	NON-COMPETING CONTINUATION	$348,435
														Subtotal = $348,435

Issue Date FY: 2023 ( Subtotal = $754,130 )
2023	2023	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	4	3/29/2023	NON-COMPETING CONTINUATION	$754,130
														Subtotal = $754,130

Issue Date FY: 2022 ( Subtotal = $980,741 )
2022	2022	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	4/8/2022	NON-COMPETING CONTINUATION	$761,873
2022	2022	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	3	8/29/2022	SUPPLEMENT FOR EXPANSION	$218,868
														Subtotal = $980,741

Issue Date FY: 2021 ( Subtotal = $720,419 )
2021	2021	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	4/26/2021	NON-COMPETING CONTINUATION	$720,419
														Subtotal = $720,419

Issue Date FY: 2020 ( Subtotal = $743,299 )
2020	2020	TRUSTEES OF TUFTS COLLEGE	136 HARRISON AVE	BOSTON	MA	02111	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	5/15/2020	NEW	$743,299
														Subtotal = $743,299

Grand Total All Awards = $3,547,024

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Development and Field Testing of a Novel Reservoir Targeted Antibiotic Against Borrelia burgdorferi

Award Number: R01AI152210

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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