- Human Asymptomatic Epitope Peptide/CXCL10-Based Prime/Pull Vaccine Induces Herpes Simplex Virus-Specific Gamma Interferon-Positive CD107+ CD8+ T Cells That Infiltrate the Corneas and Trigeminal Ganglia of Humanized HLA Transgenic Rabbits and Protect against Ocular Herpes Challenge. [Journal Article]
- JVJ Virol 2018 08 15; 92(16)
- Herpes simplex virus 1 (HSV-1) is a prevalent human pathogen that infects the cornea, causing potentially blinding herpetic disease. A clinical herpes vaccine is still lacking. In the present study, ...
Herpes simplex virus 1 (HSV-1) is a prevalent human pathogen that infects the cornea, causing potentially blinding herpetic disease. A clinical herpes vaccine is still lacking. In the present study, a novel prime/pull vaccine was tested in a human leukocyte antigen (HLA) transgenic rabbit model of ocular herpes (HLA Tg rabbits). Three peptide epitopes were selected, from the HSV-1 membrane glycoprotein C (UL44400-408), the DNA replication binding helicase (UL9196-204), and the tegument protein (UL25572-580), all preferentially recognized by CD8+ T cells from "naturally protected" HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who never had recurrent corneal herpetic disease). HLA Tg rabbits were immunized with a mixture of these three ASYMP CD8+ T cell peptide epitopes (UL44400-408, UL9196-204, and UL25572-580), which were delivered subcutaneously with CpG2007 adjuvant (prime). Fifteen days later, half of the rabbits received a topical ocular treatment with a recombinant neurotropic adeno-associated virus type 8 (AAV8) vector expressing the T cell-attracting CXCL10 chemokine (pull). The frequency and function of HSV-specific CD8+ T cells induced by the prime/pull vaccine were assessed in the peripheral blood, cornea, and trigeminal ganglion (TG). Compared to the cells generated in response to peptide immunization alone, the peptide/CXCL10 prime/pull vaccine generated frequent polyfunctional gamma interferon-positive (IFN-γ+) CD107+ CD8+ T cells that infiltrated both the cornea and TG. CD8+ T cell mobilization into the cornea and TG of prime/pull-vaccinated rabbits was associated with a significant reduction in corneal herpesvirus infection and disease following an ocular HSV-1 (strain McKrae) challenge. These findings draw attention to the novel prime/pull vaccine strategy for mobilizing antiviral CD8+ T cells into tissues to protect against herpesvirus infection and disease.IMPORTANCE There is an urgent need for a vaccine against widespread herpes simplex virus infections. The present study demonstrates that immunization of HLA transgenic rabbits with a peptide/CXCL10 prime/pull vaccine triggered mobilization of HSV-specific CD8+ T cells locally into the cornea and TG, the sites of acute and latent herpesvirus infections, respectively. Mobilization of antiviral CD8+ T cells into the cornea and TG of rabbits that received the prime/pull vaccine was associated with protection against ocular herpesvirus infection and disease following an ocular HSV-1 challenge. These results highlight the importance of the prime/pull vaccine strategy to bolster the number and function of protective CD8+ T cells within infected tissues.
- Herpetic eye disease study: lessons learned. [Review]
- COCurr Opin Ophthalmol 2018; 29(4):340-346
- CONCLUSIONS: HEDS established the standard of HSV ocular therapy and is still valid today. However, newer antivirals may provide easier compliance with improved bioavailability, efficacy, dosage, and tolerability. Further research is needed to prevent latency of HSV, decrease recurrences, and more effectively treat necrotizing keratitis associated with HSV.
- Herpes zoster ophthalmicus: acute keratitis. [Review]
- COCurr Opin Ophthalmol 2018; 29(4):328-333
- CONCLUSIONS: Acute zoster keratitis can lead to permanent vision loss. Early diagnosis and management may help reduce these potentially devastating complications. Oral and topical antiviral medications can play a role in managing the acute disease, and herpes zoster vaccinations are important for prevention of disease. Further research must be done to establish standards for treatment of anterior segment complications from herpes zoster.
- Adenoviral keratitis: a review of the epidemiology, pathophysiology, clinical features, diagnosis, and management. [Review]
- COCurr Opin Ophthalmol 2018; 29(4):365-372
- CONCLUSIONS: Although significant effort has been made to develop new methods for diagnosis and management, adenoviral keratitis is predominantly diagnosed clinically with prevention being the mainstay of management. The use of newer DNA analysis techniques and topical anti-inflammatory agents for treatment of corneal infiltrates show promising results, but a better understanding of the pathogenesis and clinical features can lead to more targeted methods of diagnosis and therapy.
- Surgical management of herpetic keratitis. [Review]
- COCurr Opin Ophthalmol 2018; 29(4):347-354
- CONCLUSIONS: Several options are available for surgically managing the complications of herpes keratitis. Ophthalmologists should select the optimal procedure based on the individual patient's situation. VIDEO ABSTRACT: http://links.lww.com/COOP/A28.
- Bilateral herpes simplex keratitis reactivation after lacrimal gland botulinum toxin injection. [Case Reports]
- IJIndian J Ophthalmol 2018; 66(5):697-699
- Botulinum toxin A (BTA) injections into lacrimal gland are being used for refractory epiphora due to intractable lacrimal disorders with success rates reported from 18% to 86%. Most common side effec...
Botulinum toxin A (BTA) injections into lacrimal gland are being used for refractory epiphora due to intractable lacrimal disorders with success rates reported from 18% to 86%. Most common side effects are transient ptosis and diplopia. We report a case of a 59-year-old female injected with 2.5 units of BTA injection in each lacrimal gland for functional epiphora. The patient had a history of herpes simplex viral keratitis that was quiescent for more than 2 years. After 3 weeks, she developed reactivation of viral keratitis bilaterally, which was successfully managed with antivirals and topical steroids. Reactivation of quiescent herpes simplex keratitis is a possibility after lacrimal gland BTA and caution should be exercised in such cases.
- Comparative cost evaluation of brand name and generic ophthalmology medications in Ontario. [Review]
- CJCan J Ophthalmol 2018; 53(2):173-187
- Medication cost for the same indication can vary considerably and can affect patient compliance. In this comparative cost analysis of commonly prescribed ophthalmology medications, the differences in...
Medication cost for the same indication can vary considerably and can affect patient compliance. In this comparative cost analysis of commonly prescribed ophthalmology medications, the differences in cost between generic and brand name medications as well as different medications within an individual drug class were evaluated. Eye preparations from the Ontario Drug Benefit Formulary were identified, and further agents commonly prescribed by ophthalmologists were included. The standardized prescription drug cost, which includes the cost of the medication, mark-up, and dispensing cost, was provided by Ontario Shoppers Drug Mart stores in July 2016 for 103 common medications using typical dosages and durations. Based on medication class, the highest and lowest cost medications were antiallergy agents (Zaditor [ketotifen], Vasocon [naphazoline]), antibiotic ophthalmic solutions (Vigamox [moxifloxacin], generic ciprofloxacin), oral antibiotics (Cipro [ciprofloxacin], generic cephalexin), antibiotic ophthalmic ointments (generic erythromycin, Tobrex [tobramycin]), antiviral treatment (Valtrex [oral valacyclovir], Viroptic [topical trifluridine]), blepharitis treatment (Zithromax [oral azithromycin], generic oral tetracycline), beta-adrenergic inhibitors (Timoptic [topical timolol], generic topical timolol), topical prostaglandin analogues (Xalatan [latanoprost], generic travoprost), oral carbonic anhydrase inhibitors (methazolamide, acetazolamide), topical carbonic anhydrase solutions (Trusopt preservative-free [dorzolamide], Azopt [brinzolamide]), topical alpha-adrenergic agonists (Alphagan [brimonidine], generic brimonidine), topical muscarinic agonists (Isopto carpine [pilocarpine], Diocarpine [pilocarpine]), topical combination glaucoma agents (Cosopt [dorzolamide-timolol], generic dorzolamide-timolol), topical lubricants (Lacri-lube, Isopto tears), topical nonsteroidal anti-inflammatory drugs (Acuvail [ketorolac], Ilevro [nepafenac]), and steroids (Durezol [difluprednate], Pred mild [prednisolone]). Substantial cost differences exist between ophthalmology medications of the same class. We encourage ophthalmologists to be aware of the associated costs of the medications they prescribe and to use this information in their decision making.
- Topical Interferon Alpha-2b Induced Reactive Lymphoid Hyperplasia Masquerading as Orbital Extension of Ocular Surface Squamous Neoplasia. [Case Reports]
- CCornea 2018; 37(6):796-798
- CONCLUSIONS: Excisional biopsy of the lesions confirmed benign reactive lymphoid hyperplasia and resolved with no recurrence.
- Reactivation of herpes simplex viral keratitis following the botulinum toxin injection. [Case Reports]
- IJIndian J Ophthalmol 2018; 66(2):306-308
- We describe a case of 55-year-old male farmer presented with recurrent corneal abrasions with a spastic entropion in the left eye. Superior cornea showed typical nummular opacities suggestive resolve...
We describe a case of 55-year-old male farmer presented with recurrent corneal abrasions with a spastic entropion in the left eye. Superior cornea showed typical nummular opacities suggestive resolved herpetic eye diseases. On further enquiry, he had similar episodes in the past. Contralateral eye was essentially normal. Following the botulinum toxin injection for the management of spastic entropion, subject developed reactivation of herpetic necrotizing stromal keratitis. Diagnostic corneal scrapings were negative for herpes simplex virus-1 antigen by immunofluorescence assay and for DNA by molecular techniques. The case was successfully managed with topical steroids and antiviral medications.
New Search Next
- Intra-cameral level of ganciclovir gel, 0.15% following topical application for cytomegalovirus anterior segment infection: A pilot study. [Journal Article]
- PlosPLoS One 2018; 13(1):e0191850
- CONCLUSIONS: Ganciclovir levels in the aqueous humor was below the 50% inhibitory dose (ID50) for CMV replication, following topical application of the ganciclovir gel, 0.15%.