# Efficacy of novel reservoir-host targeted bait formulations against a tick-borne pathogen

> **NIH NIH R01** · UNIVERSITY OF TEXAS SAN ANTONIO · 2021 · $375,000

## Abstract

Lyme disease is the most common tick-borne illness in the US. Currently, there are no vaccines available to
prevent Lyme disease and antibacterial therapy is the treatment of choice. The disease is caused by a
spirochete, Borrelia burgdorferi, which is maintained in nature through an enzootic cycle involving a tick vector
and a variety of vertebrate hosts. Regulation of gene expression in B. burgdorferi in response to environmental
cues prevalent in these highly divergent hosts is critical for pathogen survival and transmission between the
tick vector and vertebrate hosts. Deletion of Borrelia host-adaptation Regulator (BadR) and site-specific
replacement of 8 critical residues of Carbon Storage Regulator A result in dysregulated borrelial strains that
hyper-express a variety of lipoproteins. Purified Borrelial Lipoproteins (PBLs) from these strains confer
protection when administered via parenteral route against challenge with B. burgdorferi infected Ixodes
scapularis nymphs. Consistent with the RFA-AI-19-037 “Targeted Prevention of Tickborne Diseases”, this
proposal is directed at evaluating PBLs from hyper-expression borrelial mutants as a bait-formulation to
develop a reservoir-targeted approach to interrupt the natural history of B. burgdorferi infection using
experimental (C3H/HeN) and reservoir (Peromyscus leucopus, white-footed mouse) mouse models of Lyme
disease. Use of PBLs in their native conformation circumvents the need to express these antigens as
recombinant proteins in heterologous systems or limitations in their reconstitution to reflect their proportions on
the borrelial surface. The central hypothesis of this proposal is that oral administration of PBLs protects
reservoir hosts against Bb challenge via ticks and interferes with the natural history of infection via Ixodes
scapularis ticks. This hypothesis will be tested with 3 specific aims. In Specific Aim 1, correlates of protective
immunity induced by PBLs against B. burgdorferi will be determined. Humoral immune response, levels of
borrelicidal antibodies and levels of protection against B. burgdorferi challenge via ticks induced in C3H/HeN or
P. leucopus mice following oral or parenteral administration of PBLs will be compared. In Specific Aim 2, the
levels of PBL-induced reduction in B. burgdorferi burden in ticks will be determined. The ability of naïve tick
larvae and nymphs fed on PBL-immunized mice to acquire and transmit B. burgdorferi to naïve mice will be
ascertained to establish a strategy to interfere with the natural history of infection. In Specific Aim 3, several
adjuvants and novel strains of B. burgdorferi expressing lipoproteins with properties to increase the potency of
a single dose, oral, reservoir bait vaccine will be evaluated. These studies are novel in exploiting the
components of genetically defined borrelial mutants in conjunction with adjuvants that increase the potency of
PBLs administered as bait formulations to interfere with natural life cycle ...

## Key facts

- **NIH application ID:** 9990202
- **Project number:** 1R01AI152233-01
- **Recipient organization:** UNIVERSITY OF TEXAS SAN ANTONIO
- **Principal Investigator:** Janakiram Seshu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $375,000
- **Award type:** 1
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990202

## Citation

> US National Institutes of Health, RePORTER application 9990202, Efficacy of novel reservoir-host targeted bait formulations against a tick-borne pathogen (1R01AI152233-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9990202. Licensed CC0.

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