Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes

Straus, Stephen E.; Savarese, Barbara; Krause, Philip R.; Kost, Rhonda G.; Meier, Jeffery L.; Corey, Lawrence; Barnum, Gail; Burke, Rae Lyn; Sekulovich, Rose E.; Adair, Suzanne F.; Dekker, Cornelia L.

doi:10.1016/s0140-6736(94)92581-x

Cited by 191 publications

(94 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Most have been safe and have induced a measurable immune response. Although the first study of a recombinant gD2 vaccine adjuvanted with alum reduced the rate of virologically confirmed recurrences (106), later studies of glycoprotein vaccines failed to replicate that effect (107). Unlike the prophylactic vaccine studies, shedding data from our group indicate that the pivotal therapeutic vaccine studies can be performed efficiently with fewer than 100 individuals if viral shedding is used as an endpoint (33), whereas prophylactic vaccination studies require a much larger sample size.…”

Section: Human Clinical Trials Prophylactic Vaccines Testing Prophylmentioning

confidence: 90%

HSV-2: in pursuit of a vaccine

Johnston

Koelle²,

Wald³

2011

J. Clin. Invest.

126

111

View full text Add to dashboard Cite

Herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually transmitted infections worldwide. In addition to recurrent genital ulcers, HSV-2 causes neonatal herpes, and it is associated with a 3-fold increased risk for HIV acquisition. Although many HSV-2 vaccines have been studied in animal models, few have reached clinical trials, and those that have been tested in humans were not consistently effective. Here, we review HSV-2 pathogenesis, with a focus on novel understanding of mucosal immunobiology of HSV-2, and vaccine efforts to date, in an attempt to stimulate thinking about future directions for development of effective prophylactic and therapeutic HSV-2 vaccines.

show abstract

Section: Human Clinical Trials Prophylactic Vaccines Testing Prophylmentioning

confidence: 90%

HSV-2: in pursuit of a vaccine

Johnston

Koelle²,

Wald³

2011

J. Clin. Invest.

126

111

View full text Add to dashboard Cite

show abstract

“…However, in the two most recent phase II/III clinical trials, the delivery of gD with the clinical adjuvants MF59 and alum-monophosphoryl lipid A only induced moderate and transient protection or only protected previously uninfected women while failing to protect men or HSV-1-seropositive women (4,10,17,18). In both trials, the HSV-specific Ab responses were similar to those of natural HSV infection.…”

mentioning

confidence: 94%

HLA-A*0201-Restricted CD8+ Cytotoxic T Lymphocyte Epitopes Identified from Herpes Simplex Virus Glycoprotein D

Chentoufi

Zhang

Lamberth³

et al. 2008

The Journal of Immunology

140

View full text Add to dashboard Cite

Evidence obtained from both animal models and humans suggests that T cells specific for HSV-1 and HSV-2 glycoprotein D (gD) contribute to protective immunity against herpes infection. However, knowledge of gD-specific human T cell responses is limited to CD4+ T cell epitopes, with no CD8+ T cell epitopes identified to date. In this study, we screened the HSV-1 gD amino acid sequence for HLA-A*0201-restricted epitopes using several predictive computational algorithms and identified 10 high probability CD8+ T cell epitopes. Synthetic peptides corresponding to four of these epitopes, each nine to 10 amino acids in length, exhibited high-affinity binding in vitro to purified human HLA-A*0201 molecules. Three of these four peptide epitopes, gD53–61, gD70–78, and gD278–286, significantly stabilized HLA-A*0201 molecules on T2 cell lines and are highly conserved among and between HSV-1 and HSV-2 strains. Consistent with this, in 33 sequentially studied HLA-A*0201-positive, HSV-1-seropositive, and/or HSV-2-seropositive healthy individuals, the most frequent and robust CD8+ T cell responses, assessed by IFN-γ ELISPOT, CD107a/b cytotoxic degranulation, and tetramer assays, were directed mainly against gD53–61, gD70–78, and gD278–286 epitopes. In addition, CD8+ T cell lines generated by gD53–61, gD70–78, and gD278–286 peptides recognized infected target cells expressing native gD. Lastly, CD8+ T cell responses specific to gD53–61, gD70–78, and gD278–286 epitopes were induced in HLA-A*0201 transgenic mice following ocular or genital infection with either HSV-1 or HSV-2. The functional gD CD8+ T cell epitopes described herein are potentially important components of clinical immunotherapeutic and immunoprophylactic herpes vaccines.

show abstract

“…Although several trials have been promising, there remain barriers to both the development of a vaccine and its implementation. [42][43][44][45][46][47] The chief limitation to this analysis was our reliance on ICD codes, which are subject to misclassification and provide no information on the characteristics of the infection, such as the infecting viral type. Some researchers have used broader ICD-9 coding and included probable cases of HSV on the basis of signs and symptoms suggestive of herpes infection.…”

Section: Figurementioning

confidence: 99%

Infant Deaths Due To Herpes Simplex Virus, Congenital Syphilis, and HIV in New York City

Sampath¹,

Maduro

Schillinger

2016

Pediatrics

View full text Add to dashboard Cite

BACKGROUND: Neonatal infection with herpes simplex virus (HSV) is not a nationally reportable disease; there have been few population-based measures of HSV-related infant mortality. We describe infant death rates due to neonatal HSV as compared with congenital syphilis (CS) and HIV, 2 reportable, perinatally transmitted diseases, in New York City from 1981 to 2013. METHODS:We identified neonatal HSV-, CS-, and HIV-related deaths using International Classification of Diseases (ICD) codes listed on certificates of death or stillbirth issued in New York City. Deaths were classified as HSV-related if certificates listed (1) any HSV ICD-9/ICD-10 codes for deaths ≤42 days of age, (2) any HSV ICD-9/ICD-10 codes and an ICD code for perinatal infection for deaths at 43 to 365 days of age, or (3) an ICD-10 code for congenital HSV. CS-and HIV-related deaths were those listing any ICD code for syphilis or HIV.RESULTS: There were 34 deaths due to neonatal HSV (0.82 deaths per 100 000 live births), 38 from CS (0.92 per 100 000), and 262 from HIV (6.33 per 100 000). There were no CS-related deaths after 1996, and only 1 HIV-related infant death after 2004. The neonatal HSV-related death rate during the most recent decade (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013) was significantly higher than in previous years. CONCLUSIONS:The increasing neonatal HSV-related death rate may reflect increases in neonatal herpes incidence; an increasing number of pregnant women have never had HSV type 1 and are therefore at risk of acquiring infection during pregnancy and transmitting to their infant.

show abstract

Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes

Cited by 191 publications

References 24 publications

HSV-2: in pursuit of a vaccine

HSV-2: in pursuit of a vaccine

HLA-A*0201-Restricted CD8+ Cytotoxic T Lymphocyte Epitopes Identified from Herpes Simplex Virus Glycoprotein D

Infant Deaths Due To Herpes Simplex Virus, Congenital Syphilis, and HIV in New York City

Contact Info

Product

Resources

About