Immunomodulator-Mediated Enhancement of Anti-HIV-Specific Immune Response Mucosal transmission is the principal route of HIV infection. It has been shown that the mucosal early innate interferon response plays an important role against HIV infection. However, the mucosal immune response against HIV would be more effective if the neutralizing secretory immunoglobulins A and G response could be enhanced. It has been reported that highly exposed, persistently seronegative patients such as Gambian sex workers, and partners of HIV infected persons who have unprotected sexual relations exhibit higher Gag, Pol and Nef-specific T cell IFN-gamma responses in cervical mucosa, as compared to HlV-seropositive patients [3]. Moreover, several groups have shown that Gag induces an HIV-specific T-cell and IgA immune responses at mucosal sites of lung and vaginal tract [4], besides that Gag [5], [6], [7], [8], Nef [8] and Pol [8] have been used in numerous mucosal immunization protocols. Therefore, the selection of Gag, Nef and Pol as antigens in combination with a mucosal immunization approach is expected to have a positive impact in the HIV-specific immune responses. DNA based vaccines are known to elicit both: cell- and humoral mediated immune responses, however there is a need to increase the amplitude of their response in humans. On this project, we will determine the immunomodulatory effect of PAI (a polyantigenic immunopotentiator consisting of a mixture of influenza and respiratory vaccines that was proven to have anticancer and anti-HIV activities) in the enhancement of the HIV-specific immune response on a DNA vaccination platform, after vaccination of humanized HLA-A2.transgenic mice. Cell- and humoral-mediated immune responses, as measured by ELISPOT and ICC analysis in these mice, will be correlated with control of viremia after qPCR analysis of serum from pseudotyped vaccinia infected mice. We hypothesize that the Polyantigenic Immunomodulator, previously tested in our laboratory, will enhance the HlV-gag, nef and pol specific mediated immune responses, after a DNA based mucosal immunization in mice. Moreover, the facts that humanized HI_A-A2.1 mice, which possess the most common human haplotype in North America, will be used as the in vivo model, and that PAI is formulated from components currently used in humans;will build a pathway towards a clinical application of this project. We therefore expect that these results could be moved easily and safely into the clinics, and therefore, could be tested in humans.

Public Health Relevance

Cell- and humoral-mediated control of HIV infection by an adjuvant-enhanced mucosal DNA vaccine is an approach that could easily be worldwide administered. Public Health will be improved by this vaccine, as control of HIV viremia will have a direct impact on HIV-related diseases, improving the quality of life of the whole affected population, and decreasing the costs of health related services.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Research Centers in Minority Institutions Award (G12)
Project #
5G12MD007583-28
Application #
8573404
Study Section
Special Emphasis Panel (ZRR1-RI-B)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
28
Fiscal Year
2013
Total Cost
$122,406
Indirect Cost
$40,649
Name
Universidad Central Del Caribe
Department
Type
DUNS #
090534694
City
Bayamon
State
PR
Country
United States
Zip Code
00960
Buchacz, Kate; Lau, Bryan; Jing, Yuezhou et al. (2016) Incidence of AIDS-Defining Opportunistic Infections in a Multicohort Analysis of HIV-infected Persons in the United States and Canada, 2000-2010. J Infect Dis 214:862-72
Fred-Jiménez, Ruth M; Arroyo-Ávila, Mariangelí; Mayor, Ángel M et al. (2016) Clinical Manifestations Associated with Overweight/Obesity in Puerto Ricans with Fibromyalgia Syndrome. J Obes 2016:1379289
Méndez-González, Miguel P; Kucheryavykh, Yuriy V; Zayas-Santiago, Astrid et al. (2016) Novel KCNJ10 Gene Variations Compromise Function of Inwardly Rectifying Potassium Channel 4.1. J Biol Chem 291:7716-26
Santiago-Rodríguez, Eduardo J; Mayor, Angel M; Fernández-Santos, Diana M et al. (2016) Profile of HIV-Infected Hispanics with Pancytopenia. Int J Environ Res Public Health 13:ijerph13010038
Inyushin, M; Kucheryavih, Yu; Kucheryavih, L et al. (2016) Superparamagnetic Properties of Hemozoin. Sci Rep 6:26212
Morales-Cruz, Moraima; Cruz-Montañez, Alejandra; Figueroa, Cindy M et al. (2016) Combining Stimulus-Triggered Release and Active Targeting Strategies Improves Cytotoxicity of Cytochrome c Nanoparticles in Tumor Cells. Mol Pharm 13:2844-54
Rivera Rivera, Amilcar; Castillo-Pichardo, Linette; Gerena, Yamil et al. (2016) Anti-Breast Cancer Potential of Quercetin via the Akt/AMPK/Mammalian Target of Rapamycin (mTOR) Signaling Cascade. PLoS One 11:e0157251
Althoff, Keri N; Rebeiro, Peter F; Hanna, David B et al. (2016) A picture is worth a thousand words: maps of HIV indicators to inform research, programs, and policy from NA-ACCORD and CCASAnet clinical cohorts. J Int AIDS Soc 19:20707
Miranda-Diaz, Christine; Betancourt, Elba; Ruiz-Candelaria, Yelitza et al. (2016) Barriers for Compliance to Breast, Colorectal, and Cervical Screening Cancer Tests among Hispanic Patients. Int J Environ Res Public Health 13:ijerph13010021
Zueva, Lidia; Golubeva, Tatiana; Korneeva, Elena et al. (2016) Foveolar Müller Cells of the Pied Flycatcher: Morphology and Distribution of Intermediate Filaments Regarding Cell Transparency. Microsc Microanal 22:379-86

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