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dc.contributor.author Rubio, Jennifer en
dc.date.accessioned 2018-02-09T20:45:03Z en
dc.date.available 2018-02-09T20:45:03Z en
dc.date.issued 2018-02-09 en
dc.identifier.uri http://hdl.handle.net/10211.3/199941 en
dc.description.abstract Infections caused by Herpes Simplex 2 (HSV-2) manifest as painful, genital lesions with frequent recurrent episodes that cannot be cured by antiviral drug therapy, underscoring the need for an effective vaccine. In our laboratory, we previously found that the HSV gD envelope protein (gD1-306-HD) in a liposomal vaccine could generate significant protection against intravaginal HSV-2 challenge in a murine model. The vaccines that our laboratory is developing focuses on three of the most immunogenic amino acid sequences within the gD protein (gD3pep). These studies aim to test the efficacy of gD1-306-HD, when incorporated into liposomes, or gD3pep-Cys with CMI liposomes or gD3pep-HD liposomal vaccines in combination with different adjuvants against an intravaginal HSV-2 challenge in Swiss Webster or BALB/c mice. The adjuvants bind with different receptors and include Monophosphoryl Lipid A (MPL) that binds with the TLR4 receptor, Lipidated or Non-Lipidated cyclic dinucleotide (CDN) that binds with the STING receptor, Lipidated Tucaresol (LT1) that binds with T cell receptors, 1V270 that binds with the TLR7 receptor and carbohydrates Trehalose Dibehenate (TDB) and Mifamurtide (Mif) which bind to C-type lectin receptor or NOD-like receptor, respectively. Liposomal vaccines were administered 3X subcutaneously to all mice on d0, d28, and d56. Negative controls were liposomes with no gD3pep or just phosphate buffered saline (PBS). Serum was collected from all groups on d59 and d60 to assess Neutralizing Antibody Titers and to perform ELISA anti-gD3pep IgG Isotyping. Splenocytes were also collected on d59 and d60 and used to investigate cytokine production via Luminex and ELISPOT assays. Mice were treated subcutaneously with Depo-Provera on d63 and d69. Treated mice were challenged intravaginally with 10X LD50 HSV-2 on d70 and monitored for morbidity 2X/day for 28 days. Vaginal swabs were collected on d72 to assess the viral burdens using a Plaque Forming Unit assay. All adjuvants, when incorporated into gD1-306-HD liposomes, or gD3pep-Cys CMI liposomes or gD3pep-HD liposomes generated significant protection against an HSV-2 intravaginal challenge based on prolonged survival and decreased viral burden. gD3pep-Cys liposomes with adjuvants 1V270, NLipCDN, LT1, MPL provided protection via stimulation and production of both Th1 and Th2 cytokines. Based on IgG isotyping ratios, gD3pep-Cys liposomes with the carbohydrates or PEP1 liposomes favored a protective Th2 response whereas PEP2 and PEP3 liposomes favored non-protectiveTh1 responses. Notably, gD3pep-Cys in CMI liposomes without adjuvant stimulated a protective immune response and suggested there is no advantage in using an adjuvant since gD3pep-Cys CMI liposomes without an adjuvant had consistently equal protection. We hypothesize that the CMI liposomes have some immunostimulatory properties and when combined with a multimeric display of the gD3pep antigen on the liposome surface, the liposomes are readily taken up by the antigen presenting cells. These observations underscore the important role that these CMI liposomes, combined with the right epitope, play in generating an effective immune response against HSV infections. Overall, the gD3 liposomes with any of the adjuvants were protective but the degree of protection and type of immune response varied depending upon the dose and adjuvant used. en
dc.description.sponsorship Molecular Express Inc., NIH RISE 1R25GM113748-01 en
dc.language.iso en en
dc.publisher California State Polytechnic University, Pomona en
dc.rights.uri http://www.cpp.edu/~broncoscholar/rightsreserved.html en
dc.subject vaccine en
dc.subject HSV en
dc.subject liposomes en
dc.subject herpes en
dc.title Efficacy Against Vaginal Herpes Virus Infection Using Adjuvants in a gD Tripeptide Liposomal Vaccine en
dc.type Thesis en
dc.contributor.department Biological Sciences en
dc.description.degree M.S. en
dc.contributor.committeeMember Buckley, Nancy en
dc.contributor.committeeMember Durrant, Douglas en
dc.rights.license All rights reserved en


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