# Development of a Safe and Potent Vaccine Against Melioidosis using the LVS dcapB Vector Platform

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $775,812

## Abstract

PROJECT SUMMARY/ABSTRACT
 Burkholderia pseudomallei (Bp), an environmental bacterium capable of infecting humans and animal
hosts, is the causative agent of melioidosis, a highly fatal disease endemic in many tropical areas. In addition
to its significant public health burden in endemic regions, causing ~89,000 deaths annually, Bp is categorized
as a Tier 1 Select Agent of bioterrorism, in large part because inhalation of low doses of Bp can cause rapidly
fatal pneumonia. As naturally acquired melioidosis is often difficult to diagnose and requires very lengthy
treatment, and as post-exposure prophylaxis is not a practical public health policy for countering an outbreak of
pneumonic melioidosis from a bioterrorist attack, a safe and effective pre-exposure vaccine would be highly
beneficial in both circumstances. Currently, there are no licensed vaccines against Bp. Hence, a vaccine
against Bp would be of great benefit to people living in endemic regions, travelers, and military personnel
stationed in these areas, and it would also reduce the risk from an intentional release in a bioterrorist attack.
 The goal of this application is to develop a safe and highly potent vaccine against Bp, suitable for both
biodefense and public health purposes, based on a readily expandable single vector platform vaccine.
Specifically, we shall use a novel, safe, yet potent live attenuated vector, LVS ΔcapB. The LVS ΔcapB vector,
developed in this laboratory, is a further attenuated version (>10,000 fold less virulent in mice) of a multi-
deletional Francisella tularensis vaccine (F. tularensis subsp. holarctica Live Vaccine Strain; LVS) already
extensively tested in humans; hence, LVS ΔcapB is anticipated to be exceedingly safe. Moreover, recombinant
vaccines comprising this vector have been shown to induce potent humoral and cell-mediated (including both
CD4+ and CD8+) immune responses, all likely important to long-lasting potent immunoprotection against Bp.
In preliminary studies, homologous boosting with rLVS ΔcapB vaccines expressing immunoprotective Bp 
antigens has already demonstrated impressive protective efficacy against respiratory challenge with virulent Bp in
sensitive BALB/c mice; protection was superior to the unlicensed attenuated Bp82 vaccine, which is unlikely to
be approved because of concerns about reversion to virulence and the possibility of causing chronic disease.
 To accomplish our goal of developing a safe and highly potent vaccine against Bp, we shall a) construct
optimized rLVS ΔcapB vaccines expressing multiple immunoprotective Bp antigens as fusion proteins; b)
evaluate the vaccines systematically in vitro for protein expression, growth kinetics, and stability; c) evaluate
the vaccines administered by different routes for safety, dissemination, clearance, and stability in both immune
competent and immune deficient mice; d) evaluate protective efficacy against challenge with highly virulent Bp
by the respiratory (IN) route, the route of...

## Key facts

- **NIH application ID:** 10159194
- **Project number:** 5R01AI141390-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** MARCUS AARON HORWITZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $775,812
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159194

## Citation

> US National Institutes of Health, RePORTER application 10159194, Development of a Safe and Potent Vaccine Against Melioidosis using the LVS dcapB Vector Platform (5R01AI141390-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10159194. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*