Therapeutic Ocular HSV Vaccine in HLA Transgenic Rabbits

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Staining and confocal imaging of corneal nerves. The quantification of HSV by PCR has also been shown to have useful applications. Although this finding strongly suggests ubiquitous expression of HLA-A*0201 molecules in these rabbits, we further examined HLA-A*0201 expression in corneas, TG and PBMC. ROLE OF ANIMAL MODELS IN HERPES SIMPLEX VACCINE DEVELOPMENT Reliable animal models of herpes infection and disease are the key to the development of an effective therapeutic vaccine against HSV-1 and HSV-2. Host genetic makeup also plays a role in establishment of HSV-1 latency. Reports from Africa[21-23] on AIDS/ HIV infection also disclosed some of these differences. 5G, PFig.

The PD-1, Tim-3, and IL-21 are markers for T-cell exhaustion and a primary factor leading to exhaustion. Ophthalmology 1996; 103:1483–92. 2001 Oct;323(7318):935. If you encounter a skeptical patient, use an anterior segment image to educate the patient on his condition. Koskas P, Héran F. No cases of keratoconus or retinal detachment were observed in our study. Rabbits, HSV-1 intermittently reactivates from latently infected primary sensory neurons, leads to peripheral shedding of infectious virus and recurrent corneal disease similar to humans [75].

Weitgasser et al. GFP expression in mouse eyes was directly proportional to the amount of corneal scarification, but the extent of green fluorescent viral infection did not appreciably differ between C57BL/6 and BALB/c mice (Fig. Clinicians should typically try to confirm a GU diagnosis with a nucleic acid amplification test (NAAT), she said. Sabbaga et al.23 used in situ hybridization, tear film, whole-cell, and cell-free cultures to demonstrate HSV-1 (strain RE) corneal latency. The PCR products were analyzed by 3% agarose gel electrophoresis. Therefore, the selected anti-human CD8 mAb has been pretested for not affecting tetramer binding. Immunostainings for nonphosphorylated neurofilament H were done as described below following a blocking reaction in 1% H2O2 in 0.1 M Tris-buffered saline (TBS) and an incubation in 5% normal horse serum with 0.3% Triton X-100 in TBS for 1 h.

Eighteen of 19 cell-culture negative cases (95%) and 28 of 28 (100%) cell-culture positive cases [total=98% (46 of 47)] were eventually diagnosed and treated as active HSV infection based on laboratory results and clinical data. They demonstrate that human herpesviruses may have evolved a common mechanism to exploit a phagocytosis-like entrapment to gain entry into ocular cells. tegument proteins of herpes simplex virus. Genital herpes is transmitted through direct skin-to-skin contact during vaginal, anal, and oral sex. The simplest vaccine configuration capable of effective delivery of the selected sets of epitopes will also be determined. (3). We will assess whether the number/function of HSV- and epitope- specific CD8+ T cells induced in vivo correlates with protection from spontaneous virus shedding in tears and ocular disease.

53. Greater than 90% of ocular HSV infections are due to HSV type 1 (HSV-1). Ocular surgery for HZO-related complications is performed only after adequately stabilizing pre-existing ocular inflammation, raised intraocular pressure, dry eye, neurotrophic keratitis, and lagophthalmos. This finding suggests that a vaccine or immunotherapy that contains asymptomatic epitopes may promote the expansion of asymptomatic T cells, while the inclusion of symptomatic epitopes might promote immunopathological responses. These findings should guide the development of a safe and effective T cell–based herpes vaccine. In contrast, SYMP patients had frequent less-differentiated central memory CD8(+) T cells (TCM cells) (CD45RA(low) CCR7(high) CD44(low) CD62L(high)). We recently reported that these peptides are highly recognized by CD8+ T cells from “naturally” protected HSV-1–seropositive healthy ASYMP individuals (who have never had clinical herpes disease).

METHODS: Mixtures of three ASYMP CD8+ T-cell peptides derived from either HSV-1 gB, VP11/12, or VP13/14 were delivered subcutaneously to different groups of HLA-Tg rabbits (n = 10) in incomplete Freund’s adjuvant, twice at 15-day intervals. The long term goal of this competitive renewal application is to develop an effective vaccine that will produce protective immunity against ocular herpes. However, the possible role of CD8(+) T cells, specific to HLA-restricted gB epitopes, in protective immunity seen in HSV-1-seropositive asymptomatic (ASYMP) healthy individuals (who have never had clinical herpes) remains to be determined. By picking the right accessories you can make your interpretation of Hermione stand out from the crowd. No herpes simplex vaccine is currently available for use in humans. We have dissected the phenotype and the function of HSV-1 glycoprotein B- (gB-) specific CD8+ T cells from HLA-A*02:01 positive, HSV-1 seropositive asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) and symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent ocular herpes disease). Introduction A staggering number of individuals carry HSV-1 and/or HSV-2 that cause a wide range of diseases throughout their life (1–5).

Herpes simplex virus 1 (HSV-1) glycoprotein B (gB)-specific CD8+ T cells protect mice from herpes infection and disease. Most blinding ocular herpetic disease is due to reactivation of herpes simplex virus 1 (HSV-1) from latency rather than to primary acute infection.