This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Smallpox is a threat in an event of a bioterrorist attack, therefore it is important to develop a safe vaccine against this virus. There is an important population of non-vaccinated immunocompromised people that could not be safely vaccinated with the current vaccine. Within these are patients of transplants, under immunosupressive therapy, pregnant women, and the elderly. We are interested in the development of a safer vaccine that protects the population against a possible attack. We hypothesize that the adjuvant-mediated enhancement of the molecular antigen immune response will control the viral burden on infected mice. However, as smallpox is only one of possible threats, this project will provide an excellent model to test the hypothesis of a molecular adjuvant that will help set up a system that could be applied to other Category A, B and C Priority Pathogens. Mice will be immunized with plasmid DNA encoding for the vaccinia virus proteins C7L and A55R genes that are non structural proteins known to generate a cellular immune response, and the recently discovered E6R and L3L core proteins. The immunology of those molecules has not been tested to the best of our knowledge. Animals will be vaccinated with each construct individually or combined with two molecular adjuvants, the chemokine MIP-1-alpha and another construct which encodes for the dendritic cell-specific growth factor Flt-3L, a combination that is known to increase the recruitment and expansion of dendritic cells. To the best of our knowledge, this combination of molecular adjuvants has never been tested in the context of smallpox vaccination. Cell- and humoral-mediated immune responses from each antigen will be determined by ELISPOT and ELISA, respectively. Molecular mapping of each antigen will be performed to identify dominant epitopes. Animals will be challenged with a lethal dose of vaccinia virus, and the viral load will be determined by qPCR analysis. Memory, activation and proliferation will be determined to detect the long-lasting effect of each antigen on the induction of an immune response. Strong cellular and humoral immune responses against vaccinia virus are expected so that protecting immune memory could be developed without the hazard of being exposed to live virus.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016470-11
Application #
8360153
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
2011-06-01
Project End
2012-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
11
Fiscal Year
2011
Total Cost
$102,608
Indirect Cost
Name
University of Puerto Rico Rio Piedras
Department
Type
DUNS #
090051616
City
San Juan
State
PR
Country
United States
Zip Code
00926
Cantres-Rosario, Yisel M; Acevedo-Mariani, Frances M; Pérez-Laspiur, Juliana et al. (2017) Microwave & magnetic proteomics of macrophages from patients with HIV-associated cognitive impairment. PLoS One 12:e0181779
Mariño, Yobana A; Verle Rodrigues, José C; Bayman, Paul (2017) Wolbachia Affects Reproduction and Population Dynamics of the Coffee Berry Borer (Hypothenemus hampei): Implications for Biological Control. Insects 8:
Martínez-Rivera, Freddyson J; Pérez-Laspiur, Juliana; Santiago-Gascot, María E et al. (2017) Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids. PLoS One 12:e0180409
Zenón, Frances; Jorge, Inmaculada; Cruz, Ailed et al. (2016) 18O proteomics reveal increased human apolipoprotein CIII in Hispanic HIV-1+ women with HAART that use cocaine. Proteomics Clin Appl 10:144-55
Rivera-Rivera, Yainyrette; Vázquez-Santiago, Fabián J; Albino, Elinette et al. (2016) Impact of Depression and Inflammation on the Progression of HIV Disease. J Clin Cell Immunol 7:
Martínez-Rivera, Freddyson J; Rodriguez-Romaguera, Jose; Lloret-Torres, Mario E et al. (2016) Bidirectional Modulation of Extinction of Drug Seeking by Deep Brain Stimulation of the Ventral Striatum. Biol Psychiatry 80:682-690
Suárez-Arroyo, Ivette J; Rios-Fuller, Tiffany J; Feliz-Mosquea, Yismeilin R et al. (2016) Ganoderma lucidum Combined with the EGFR Tyrosine Kinase Inhibitor, Erlotinib Synergize to Reduce Inflammatory Breast Cancer Progression. J Cancer 7:500-11
Suárez-Arroyo, Ivette J; Feliz-Mosquea, Yismeilin R; Pérez-Laspiur, Juliana et al. (2016) The proteome signature of the inflammatory breast cancer plasma membrane identifies novel molecular markers of disease. Am J Cancer Res 6:1720-40
Wang, Hai-Yang; Huang, Kun; De Jesús, Melvin et al. (2016) Synthesis of enantiopure 1,2-azido and 1,2-amino alcohols via regio- and stereoselective ring-opening of enantiopure epoxides by sodium azide in hot water. Tetrahedron Asymmetry 27:91-100
Colon, Krystal; Perez-Laspiur, Juliana; Quiles, Raymond et al. (2016) Macrophage secretome from women with HIV-associated neurocognitive disorders. Proteomics Clin Appl 10:136-43

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