# Molecular basis of immunity to tick-borne rickettsioses

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2022 · $237,751

## Abstract

ABSTRACT
A recent study from the Centers for Disease Control and Prevention revealed a pressing health crisis for the
United States: the number of reported cases of tick-borne diseases has increased significantly during the past
two decades. Importantly, the reported annual incidence captures only a small fraction of the real number of
individuals infected with tick-borne pathogens. The broad spectrum of clinically important tick-borne diseases
includes Lyme disease, anaplasmosis, ehrlichiosis, tularemia, babesiosis, and Spotted Fever rickettsiosis.
Spotted Fever group rickettsiae include R. rickettsii (Rocky Mountain Spotted Fever, RMSF), R. conorii
(Mediterranean Spotted Fever), and R. parkeri (Rickettsia parkeri rickettsiosis) as well as many newly
discovered Rickettsia species with unknown pathogenicity. Doxycycline is considered as the antibiotic of
choice for the treatment of tick-borne rickettsiosis; however, delay in diagnosis and antibiotic treatment can
lead to severe disease and death. The search for long-term immune protection against invasive rickettsial
diseases (RMSF and epidemic typhus caused by R. prowazekii) has been a goal since the discovery of the
causative microorganisms by Dr. Howard T. Ricketts. However, whole cell live-attenuated or formalin/phenol-
inactivated vaccines generate limited protective immune responses in humans and, because of safety
concerns, are no longer considered for rickettsial vaccine development. We have developed kkaebi transposon
mutagenesis technology and studied the genetic requirements of the rickettsial intracellular life-cycle (bacterial
attachment to and invasion into host cells, escape from endo-lysosome, intracellular replication, and release
from host cells). This work determined that the polysaccharide synthesis operon (pso) is responsible for O-
antigen biosynthesis, contributes to pathogenesis, and is essential for the development of bactericidal Weil–
Felix antibodies. Immunization with carbohydrate conjugate vaccines, including the capsular polysaccharide or
the O-antigen of lipopolysaccharide, generated serotype-specific protective immunity that correlated with the
induction of bactericidal antibodies. This proposal aims to understand the adaptive immune responses to
invasive rickettsial infections and to determine the contribution of rickettsial O-antigen conjugate vaccine and
Weil–Felix antibodies toward protective immunity against tick-borne rickettsial infections.
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## Key facts

- **NIH application ID:** 10673274
- **Project number:** 3R01AI152208-02S1
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Hwan Keun Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $237,751
- **Award type:** 3
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10673274

## Citation

> US National Institutes of Health, RePORTER application 10673274, Molecular basis of immunity to tick-borne rickettsioses (3R01AI152208-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10673274. Licensed CC0.

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