AIDS is the number-one killer of African-American women between the ages of 25 and 34 in the United States. This group forms the fastest-growing cluster representing 67 percent of all ADDS cases in US. Currently, a vaccine for HIV/AIDS is not available. Since >90% of HIV transmission takes place at the mucosal surfaces, a vaccine that can elicit a potent mucosal immune response is the need of the hour. Currently, non-infectious DNA molecules are being tested but these molecules are weak sources of antigens and do not elicit a strong immune response at mucosal surfaces. Therefore, the goal of this project is to evaluate flagellin to potentiate a plasmid DNA that expresses env, gag and pol genes of HIV. The central hypothesis is that, since flagellin enhances both innate and adaptive immunity, it can potentiate immunogenicity of this DNA at cervix and vagina. The approach is to use this non-infectious HIV-DNA along with flagellin at cervix and vagina of B ALB/c mice. After two intra-vaginal applications of this DNAflagellin complex within 21 days interval, both innate and adaptive immunological responses will be evaluated. The NK cell and dendritic cell activities, and vaccine stimulated cytokine production will be analyzed. In our previous studies, this plasmid DNA has been shown to be immunogenic in muscles. However, this DNA has not been tested at mucosal surfaces. The central hypothesis will be tested and the objective of the project will be accomplished by two specific aims.
Aim 1 will test the hypothesis that HIVDNA will be able to generate a strong specific immune response at the reproductive mucosa.
Aim 2 will test the adjuvant effect of flagellin at reproductive mucosa. We anticipate that use of an immunogenic plasmid DNA along with a potent adjuvant will mount a strong immune response that will destroy HIV particles present in semen. Since flagellin also activates NK cells and dendritic cells non-specifically, we expected that it will help to destroy cell associated viruses in semen and therefore will assist specific immune responses to prevent virus transmission. It is our expectation that the resultant strategy may prove to be helpful in developing a prophylactic mucosal vaccine for HIV/AIDS thereby reducing chances of virus spread from infected to healthy individuals. Such outcomes will have profound and significant impact on preventing health disparities among minority individuals infected with HIV by providing affordable vaccine and reducing morbidity and mortality associated with HIV and AIDS.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Exploratory Grants (P20)
Project #
5P20MD002303-04
Application #
8074972
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
4
Fiscal Year
2010
Total Cost
$206,965
Indirect Cost
Name
Winston-Salem State University
Department
Type
DUNS #
071579031
City
Winston-Salem
State
NC
Country
United States
Zip Code
27110
Lee, Anna K; Corneille, Maya A; Hall, Naomi M et al. (2016) The stressors of being young and Black: Cardiovascular health and Black young adults. Psychol Health 31:578-91
Cherry, Kristina E; Hearn, Willis E; Seshie, Osborne Y K et al. (2014) Identification of Tf1 integration events in S. pombe under nonselective conditions. Gene 542:221-31
Pulgar, Victor M; Jeffers, Anne B; Rashad, Hanadi M et al. (2013) Increased constrictor tone induced by ouabain treatment in rats. J Cardiovasc Pharmacol 62:174-83
Aragon, Stephen J; Richardson, Liana J; Lawrence, Wanda et al. (2013) Nurses' Patient-Centeredness and Perceptions of Care among Medicaid Patients in Hospital Obstetrical Units. Nurs Res Pract 2013:563282
Aragon, Stephen; Vereen, Sabrina S; Slazyk, Deborah E et al. (2012) Patient-Centeredness: A Best Practice for HBCU Health Professional Education Programs. J Best Pract Health Prof Divers 5:725-738
Lara, Humberto H; Garza-Trevino, Elsa N; Ixtepan-Turrent, Liliana et al. (2011) Silver nanoparticles are broad-spectrum bactericidal and virucidal compounds. J Nanobiotechnology 9:30
Lara, Humberto H; Ixtepan-Turrent, Liliana; Garza Trevino, Elsa N et al. (2011) Use of silver nanoparticles increased inhibition of cell-associated HIV-1 infection by neutralizing antibodies developed against HIV-1 envelope proteins. J Nanobiotechnology 9:38
Mahapatro, Anil; Singh, Dinesh K (2011) Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines. J Nanobiotechnology 9:55
Logan, Exazevia M; Aileru, Azeez A; Shaltout, Hossam A et al. (2011) The functional role of PI3K in maintenance of blood pressure and baroreflex suppression in (mRen2)27 and mRen2.Lewis rat. J Cardiovasc Pharmacol 58:367-73
Aragon, Stephen J; McGuinn, Laura; Bavin, Stefoni A et al. (2010) Does pediatric patient-centeredness affect family trust? J Healthc Qual 32:23-31