Development of HSV-specific CD4+ Th1 responses and CD8+ cytotoxic T lymphocytes with antiviral activity by vaccination with the HSV-2 mutant ICP10ΔPK

Gyotoku, Takahiro; Ono, Fumitake; Aurelian, Laure

doi:10.1016/s0264-410x(02)00199-8

Cited by 32 publications

(22 citation statements)

References 87 publications

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“…The use of replication-defective vaccines, which induce antibody responses to nearly all of the viral proteins, often results in difficulties in determining whether or not patients develop asymptomatic infection after vaccination. Two such replication-defective vaccines under development are HSV-2 dl5-29, which is deleted for only ICP8 and UL5 (16,17,22), and ICP10⌬PK, which is missing 339 aa from the protein kinase domain of the large subunit of ribonucleotide reductase (3,13,21). In the case of HSV-2 dl5-29, our ability to easily measure titers of antibody to ICP8, despite the fact that it is a nonstructural protein, should allow future vaccine studies with animals to determine if asymptomatic infection has occurred after vaccination.…”

Section: Discussionmentioning

confidence: 99%

“…gB has also been used in candidate subunit vaccines (14,34). Two other major vaccines under development include a replication-defective HSV-2 virus deleted for ICP8 and UL5 (16,17,22) and a growthdefective virus deleted for the protein kinase domain within the large subunit of ribonucleotide reductase (3,13,21). Serologic assays for gD and gB would be useful for studying the immune response to candidate subunit vaccines.…”

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confidence: 99%

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Serological Diagnosis of Human Herpes Simplex Virus Type 1 and 2 Infections by Luciferase Immunoprecipitation System Assay

Burbelo

Hoshino

Leahy

et al. 2009

Clin Vaccine Immunol

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Highly quantitative and high-throughput serological tests for evaluation of humoral responses to herpes simplex virus 1 (HSV-1) and HSV-2 are not available. The efficacy of luciferase immunoprecipitation system (LIPS) assays for antibody profiling and serologic diagnosis of HSV-1 and HSV-2 infection was investigated using a panel of five recombinant HSV antigens. Plasma samples from subjects seropositive for HSV-1 and/or HSV-2 or seronegative for HSV-1 and HSV-2 that had previously been analyzed by Western blotting and the Focus Plexus immunoassay were evaluated. The LIPS test measuring anti-gG1 antibody titers was 96% sensitive and 96% specific for detecting HSV-1 infection, compared with the Focus immunoassay, and was 92% sensitive and 96% specific, compared with Western blotting. The results for the anti-gG2 LIPS test for HSV-2 precisely matched those for Western blotting, with 100% sensitivity and 100% specificity, and showed robust antibody titers in all the HSV-2-infected samples that were over 1,000 times higher than those in HSV-2-negative or HSV-1-positive samples. Antibodies to three additional HSV-2 proteins, gB, gD, and ICP8, were detected in many of the HSV-1-and/or HSV-2-infected plasma samples and showed preferentially higher immunoreactivity in HSV-2-infected plasma. The titers of antibodies to these three HSV-2 antigens also significantly correlated with each other (R ‫؍‬ 0.75 to 0.81; P < 0.0001). These studies indicate that the robust anti-gG1 and anti-gG2 antibody responses detected by LIPS assays are useful for HSV-1 and HSV-2 detection and suggest that profiling of antibody responses to a panel of HSV proteins may be useful for characterizing individual humoral responses to infection and for monitoring responses to vaccines.Herpes simplex virus (HSV) causes cold sores, genital herpes, ocular infections, and encephalitis. HSV-1 is usually transmitted by contact with oral secretions and causes most HSV orofacial infections, while HSV-2 is usually spread by sexual contact and causes most cases of genital herpes. Seroprevalence studies indicate that about 60% of adults in the United States are infected with HSV-1, with most primary infections occurring during childhood (38). In contrast, seroprevalence rates of HSV-2 vary dramatically by geographic region, with infection rates ranging from 10 to 35% of the population (19, 27), and infection usually occurs later in life, through sexual contact (19). Up to 25% of individuals infected with HSV-2 are asymptomatic and thus pose a significant risk for transmitting virus to their sexual partners (23). In addition, acquisition of HSV-1 or HSV-2 toward the end of pregnancy carries a 30 to 50% risk of neonatal herpes (5), with the potential for prenatal morbidity (6). HSV-1 and HSV-2 also establish lifelong, latent infections in the nervous system, usually in trigeminal or dorsal root ganglia (35).Of the approximately 80 gene products in the HSV-1 and HSV-2 genome (20), four glycoproteins, gB, gD, gH, and gL, are required for entry and infection of cells...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Serological Diagnosis of Human Herpes Simplex Virus Type 1 and 2 Infections by Luciferase Immunoprecipitation System Assay

Burbelo

Hoshino

Leahy

et al. 2009

Clin Vaccine Immunol

View full text Add to dashboard Cite

show abstract

“…This approach contrasts with that aimed at providing protection against vaginal challenge with the closely related HSV-2. In these studies, induction of strong Th1-type responses enhanced viral clearance, resulting in reduced incidence and severity of genital lesions (10). However, following infection of the eye, the persistence of proinflammatory cytokines following viral clearance results in continued influx of Th1 immune cells, leading to opacity and vascularization of this highly specialized, normally transparent organ (6).…”

Section: Discussionmentioning

confidence: 99%

Protection against Recurrent Ocular Herpes Simplex Virus Type 1 Disease after Therapeutic Vaccination of Latently Infected Mice

Richards

Case

Hirst

et al. 2003

J Virol

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The potential of therapeutic vaccination of animals latently infected with herpes simplex virus type 1 (HSV-1) to enhance protective immunity to the virus and thereby reduce the incidence and severity of recurrent ocular disease was assessed in a mouse model. Mice latently infected with HSV-1 were vaccinated intranasally with a mixture of HSV-1 glycoproteins and recombinant Escherichia coli heat-labile enterotoxin B subunit (rEtxB) as an adjuvant. The systemic immune response induced was characterized by high levels of virusspecific immunoglobulin G1 (IgG1) in serum and very low levels of IgG2a. Mucosal immunity was demonstrated by high levels of IgA in eye and vaginal secretions. Proliferating T cells from lymph nodes of vaccinated animals produced higher levels of interleukin-10 (IL-10) than were produced by such cells from mockvaccinated animals. This profile suggests that vaccination of latently infected mice modulates the Th1-dominated proinflammatory response usually induced upon infection. After reactivation of latent virus by UV irradiation, vaccinated mice showed reduced viral shedding in tears as well as a reduction in the incidence of recurrent herpetic corneal epithelial disease and stromal disease compared with mock-vaccinated mice. Moreover, vaccinated mice developing recurrent ocular disease showed less severe signs and a quicker recovery rate. Spread of virus to other areas close to the eye, such as the eyelid, was also significantly reduced. Encephalitis occurred in a small percentage (11%) of mock-vaccinated mice, but vaccinated animals were completely protected from such disease. The possible immune mechanisms involved in protection against recurrent ocular herpetic disease in therapeutically vaccinated animals are discussed.

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“…A similar live attenuated HSV-2 vaccine based on a replication competent ICP10 mutant is also currently Phase II clinical study by AuRix Biotech. 27 Many other vaccine strategies are also taking into account immune evasion aspects of HSV. The HSV immediate early protein ICP47 can inhibit CD8+ T cell recognition of infected cells and has a predilection to bind with transporter protein TAP and thus inhibit the transport of peptides into the endoplasmic reticulum, where they otherwise would form a complex with MHC class I molecules and be transported to the cell surface to be recognized by CD8+ CTLs.…”

Section: Dna Vaccinesmentioning

confidence: 99%

Recent advances in vaccine development for herpes simplex virus types I and II

Coleman

Shukla

2013

Human Vaccines & Immunotherapeutics

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Development of HSV-specific CD4+ Th1 responses and CD8+ cytotoxic T lymphocytes with antiviral activity by vaccination with the HSV-2 mutant ICP10ΔPK

Cited by 32 publications

References 87 publications

Serological Diagnosis of Human Herpes Simplex Virus Type 1 and 2 Infections by Luciferase Immunoprecipitation System Assay

Serological Diagnosis of Human Herpes Simplex Virus Type 1 and 2 Infections by Luciferase Immunoprecipitation System Assay

Protection against Recurrent Ocular Herpes Simplex Virus Type 1 Disease after Therapeutic Vaccination of Latently Infected Mice

Recent advances in vaccine development for herpes simplex virus types I and II

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