We propose to evaluate the use of the Newcastle disease virus (NDV) as a delivery vector for host immunization with borrelial antigens as vaccine targets. We will assess protection of NDV-immunized rodent hosts against Borrelia burgdorferi infection, known as Lyme disease or Lyme borreliosis. NDV is an avian virus that is highly immunogenic yet attenuated in mammals including primates. NDV is a safe vaccine vector for human use and anti-NDV antibodies are readily induced in human, as shown in clinical trial studies. Infectious NDV can be easily produced from transfected cDNAs by reverse genetics, a method that has been instrumental for studying basic biology and pathogenesis of the virus. In recent years, these technologies are also adopted for studies with translational goals, such as engineering NDV vectors against variety of animal and human diseases. In this proposal, we will assess if NDV-derived vectors could be an additional approach for host immunization against B. burgdorferi infection and identify protective efficacy of several newly characterized novel spirochete antigens. Our current data show that even a single immunization of rodents with recombinant NDV elicits a robust antibody response against tested borrelial antigens. We will initiate additional series of immunization studies with NDV constructs carrying several new target antigens, assess antibody development in rodent hosts and finally determine if specific antibodies in the host interfere with spirochete infectivity. If more than one antigen is promising we will combine multiple antigens in search of an additive effect. We will also perform studies for understanding the mechanism of humoral and cellular immune responses associated with host protection. Overall, these studies will contribute to the development of preventive measures against multi-organ infection caused by B. burgdorferi.

Public Health Relevance

Lyme disease or Lyme borreliosis is a serious infection caused by the pathogen Borrelia burgdorferi. We propose to test whether immunization of rodent hosts with New castle disease virus-vectored borrelial antigens, singly or in combination of multiple antigens, induce protective host immunity against B. burgdorferi infection. These studies will contribute to the development of new approaches for host immunization and identify novel vaccine targets to interfere with the infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI106059-01A1
Application #
8511948
Study Section
Vaccines Against Microbial Diseases (VMD)
Program Officer
Breen, Joseph J
Project Start
2013-02-01
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
1
Fiscal Year
2013
Total Cost
$190,000
Indirect Cost
$65,000
Name
University of Maryland College Park
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
790934285
City
College Park
State
MD
Country
United States
Zip Code
20742