A unique vaccine platform employs novel bioengineerable nanoparticles, Haloarchaeal gas vesicles (HGVs), as an adjuvant and antigen delivery system that is inexpensive, effective, and shelf-stable (requiring no refrigeration). When administered to animals, HGV nanoparticles with surface-displayed antigens produce strong long-lived immune responses. In previous work, antigens from bacterial and viral pathogens were expressed as a fusion to one of the HGV protein components and in all cases the recombinant HGVs were highly immunogenic in mice. We plan to test the effectiveness of HGVs as a vaccine vehicle against Salmonella enterica serovar Typhi, the causative agent of typhoid fever. These human pathogens remain important causes of morbidity and mortality in many countries as a result of poor sanitation, and water and food contaminated by human fecal waste. Our goal is to progress toward the development of a safe and inexpensive oral vaccine against invasive Salmonella disease that can be used in both the developing and developed world. We propose to: (a) produce multiple Salmonella protective antigens displayed on HGV nanoparticles;and (b) deliver the bioengineered HGV-vaccine antigen nanoparticles and determine their protective efficacy in a mouse model. We will also perform more in-depth immunological analyses and test protection using combinations of HGV formulations. These studies will lay the foundation for subsequent evaluation of this approach in humans as well as customize the system for prevention of other diseases. The development of a safe, oral adjuvant and vaccine delivery vehicle which is inexpensive, effective, and shelf-stable should lead to a global revolution in the prevention of infectious diseases.

Public Health Relevance

Haloarchaeal gas vesicles (HGVs) are bioengineerable nanoparticles that constitute a novel adjuvant and antigen delivery system requiring no refrigeration. HGV nanoparticles with surface-displayed antigens elicit strong, long-lived immune responses. We plan to test the effectiveness of HGVs as a vaccine vehicle using the Salmonella enterica serovar that is the causative agent of typhoid. Our goal is to progress toward the development of a safe and inexpensive oral vaccine against invasive Salmonella disease that can be used in both the developing and developed world.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
1R03AI107634-01
Application #
8570051
Study Section
Gene and Drug Delivery Systems Study Section (GDD)
Program Officer
Alexander, William A
Project Start
2013-05-25
Project End
2015-04-30
Budget Start
2013-05-25
Budget End
2014-04-30
Support Year
1
Fiscal Year
2013
Total Cost
$76,750
Indirect Cost
$26,750
Name
University of Maryland Baltimore
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Karan, Ram; DasSarma, Priya; Balcer-Kubiczek, Elizabeth et al. (2014) Bioengineering radioresistance by overproduction of RPA, a mammalian-type single-stranded DNA-binding protein, in a halophilic archaeon. Appl Microbiol Biotechnol 98:1737-47
DasSarma, Priya; Negi, Vidya Devi; Balakrishnan, Arjun et al. (2014) Haloarchaeal gas vesicle nanoparticles displaying Salmonella SopB antigen reduce bacterial burden when administered with live attenuated bacteria. Vaccine 32:4543-9