The overall goal of this application is to develop improved plague vaccines. Our proposal was developed based on our recent progress in plague vaccine studies which includes 1.) the use of a DNA immunization approach to search for additional protective antigens and 2.) the discovery of cell mediated immune responses in the protection of Y. pestis infection. Support for the current proposal will allow us to develop a unique technological platform which can combine antigen discovery, optimization of vaccine formulation, and efficient needle free intradermal delivery of subunit-based multi-gene plague vaccines into one system.
Specific Aim 1 : To continue our work using DNA immunization as a tool to screen for additional protective antigens against plague, including both the study of individual candidate antigens and the high throughput screening of animal sera which has been immunized with specialized Y. pestis strains deficient for the dominant antigens LcrV and F1. This approach exploits the availability of a newly constructed Y. pestis expression library and protein microarray techniques.
Specific Aim 2 : To study the cellular immunological mechanisms that are important for improving the protective efficacy of plague vaccines which includes the use of the DNA prime plus protein boost approach to increase the level and longevity of protective antibody responses induced by subunit plague vaccines.
Specific Aim 3 : To conduct late-phase preclinical immunogenicity and protection studies in non-human primates to prepare for a clinical study with optimized plague vaccine formulation and DNA delivery device that has been proven effective in humans. Plain, lay language summary: This study is designed to produce effective biodefense vaccines against Y. pestis, the highly lethal bacteria that causes plague, an infection that has the potential to cause a high percentage of human fatalities. This study is part of the broad biodefense effort to protect against such agents if they were to be used for bioterrorism purposes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI078073-04
Application #
8129744
Study Section
Special Emphasis Panel (ZAI1-TP-M (J1))
Program Officer
Zou, Lanling
Project Start
2008-09-15
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2011
Total Cost
$411,207
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
Zhang, Lu; Jia, Na; Li, Jun et al. (2014) Optimal designs of an HA-based DNA vaccine against H7 subtype influenza viruses. Hum Vaccin Immunother 10:1949-58
Huang, Rui; Zhang, Lu; Gu, Qin et al. (2014) Profiles of acute cytokine and antibody responses in patients infected with avian influenza A H7N9. PLoS One 9:e101788
Li, Jun; Han, Yaping; Xing, Yiping et al. (2014) Concurrent measurement of dynamic changes in viral load, serum enzymes, T cell subsets, and cytokines in patients with severe fever with thrombocytopenia syndrome. PLoS One 9:e91679
Palace, Samantha G; Proulx, Megan K; Lu, Shan et al. (2014) Genome-wide mutant fitness profiling identifies nutritional requirements for optimal growth of Yersinia pestis in deep tissue. MBio 5:
Gil, Anna; Shen, Siyuan; Coley, Scott et al. (2013) DNA vaccine prime followed by boost with live attenuated virus significantly improves antigen-specific T cell responses against human cytomegalovirus. Hum Vaccin Immunother 9:2120-32
Wang, Shixia; Lu, Shan (2013) DNA immunization. Curr Protoc Microbiol 31:18.3.1-18.3.24
Almansour, Iman; Chen, Huaiqing; Wang, Shixia et al. (2013) Cross reactivity of serum antibody responses elicited by DNA vaccines expressing HA antigens from H1N1 subtype influenza vaccines in the past 30 years. Hum Vaccin Immunother 9:2049-59
Wang, Shixia; Goguen, Jon D; Li, Fusheng et al. (2011) Involvement of CD8+ T cell-mediated immune responses in LcrV DNA vaccine induced protection against lethal Yersinia pestis challenge. Vaccine 29:6802-9
Wang, Shixia; Hackett, Anthony; Jia, Na et al. (2011) Polyvalent DNA vaccines expressing HA antigens of H5N1 influenza viruses with an optimized leader sequence elicit cross-protective antibody responses. PLoS One 6:e28757
Suguitan Jr, Amorsolo L; Cheng, Xing; Wang, Weijia et al. (2011) Influenza H5 hemagglutinin DNA primes the antibody response elicited by the live attenuated influenza A/Vietnam/1203/2004 vaccine in ferrets. PLoS One 6:e21942

Showing the most recent 10 out of 12 publications