The efficacy and safety of Skinner herpes simplex vaccine towards modulation of herpes genitalis; report of a prospective double-blind placebo-controlled trial

Skinner, G. R. B.; Turyk, Mary E.; Benson, Constance A.; Wilbanks, George D.; Heseltine, Peter N. R.; Galpin, Jeffrey E.; Kaufman, Raymond H.; Goldberg, Leonard Harry; Hartley, C. E.; Buchan, A.

doi:10.1007/s004300050043

Cited by 32 publications

(16 citation statements)

References 16 publications

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“…Vaccination against HSV-2 remains a challenge despite the many, predominantly subunit-based candidates which have been tested in the clinic [8], [9], [10], [11], [12], [14], [15], [16], [17], [18], [19], [20], [21]. ACAM529 is a replication-defective prophylactic vaccine candidate, which has proven efficacious in mice and guinea pigs [23] [24] [25] [26] [27].…”

Section: Discussionmentioning

confidence: 99%

“…Examples of randomized, placebo-controlled vaccine trials in humans include inactivated [9], [10], live attenuated [11], [12], [13], subunit [14], [15], [16], [17], [18], DNA [19] and peptide [20] approaches, which have been tested either in the prophylactic or therapeutic setting. The degree of success has been varied, although at least in one case certain populations (HSV-1 and HSV-2 seronegative women) do appear to be protected [14], [16], [21].…”

Section: Introductionmentioning

confidence: 99%

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High-Purity Preparation of HSV-2 Vaccine Candidate ACAM529 Is Immunogenic and Efficacious In Vivo

et al. 2013

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Genital herpes is a sexually transmitted infection (STI) caused by herpes simplex virus 2 (HSV-2) and to a lesser extent herpes simplex virus 1 (HSV-1). Infection by HSV-2 is life-long and is associated with significant cost to healthcare systems and social stigma despite the highly prevalent nature of the disease. For instance, the proportion of HSV-2 seropositive to seronegative adults is approximately 1 in 5 in the US and greater than 4 in 5 in some areas of sub-Saharan Africa. The replication-defective vaccine strain virus dl5-29 was re-derived using cells appropriate for GMP manufacturing and renamed ACAM529. Immunization with dl5-29 was previously reported to be protective both in mice and in guinea pigs, however these studies were performed with vaccine that was purified using methods that cannot be scaled for manufacturing of clinical material. Here we describe methods which serve as a major step towards preparation of ACAM529 which may be suitable for testing in humans. ACAM529 can be harvested from infected cell culture of the trans-complementing cell line AV529 clone 19 (AV529-19) without mechanical cell disruption. ACAM529 may then be purified with respect to host cell DNA and proteins by a novel purification scheme, which includes a combination of endonuclease treatment, depth filtration, anion-exchange chromatography and ultrafiltration/diafiltration (UF/DF). The resultant virus retains infectivity and is ∼ 200-fold more pure with respect to host cell DNA and proteins than is ACAM529 purified by ultracentrifugation. Additionally, we describe a side-by-side comparison of chromatography-purified ACAM529 with sucrose cushion-purified ACAM529, which shows that both preparations are equally immunogenic and protective when tested in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High-Purity Preparation of HSV-2 Vaccine Candidate ACAM529 Is Immunogenic and Efficacious In Vivo

et al. 2013

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“…A reduction in recurrences was suggested in response to the Lupidon H and Lupidon G vaccines, which are comprised of whole heat-killed virus from HSV-1 and HSV-2, respectively, although the results were inconclusive due to a lack of appropriate controls and the number of other interventions during the study [48]. A reduction in the number and severity of recurrences was also suggested following immunization with the Skinner vaccine, an inactivated subunit vaccine containing mixed HSV-2 glyco proteins; however, the results were not statistically significant [49]. A disabled infectious single-cycle viral vaccine carrying a deletion of glycoprotein H demonstrated initial promise in animal models [50], but failed to demonstrate protection against recurrences in a Phase II trial [51].…”

Section: New Drug Targetsmentioning

confidence: 99%

Novel approaches in fighting herpes simplex virus infections

Wilson¹,

Fakioglu²,

Herold³

2009

Expert Review of Anti-infective Therapy

100

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The development of novel strategies to eradicate herpes simplex virus (HSV) is a global public health priority. While acyclovir and related nucleoside analogues provide successful modalities for treatment and suppression, HSV remains highly prevalent worldwide and is a major cofactor fueling the HIV epidemic. HSV is the predominant cause of genital ulcerative disease, and neonatal and sporadic infectious encephalitis. Asymptomatic shedding, which occurs more frequently than previously appreciated, contributes to viral transmission. Acyclovir resistance may be problematic for immunocompromised patients and highlights the need for new safe and effective agents. Ideally, vaccines to prevent infection, drugs to inhibit the establishment of or reactivation from latency, or vaginal microbicides to prevent sexual and perinatal transmission are needed to control the epidemic. This review summarizes current therapeutic options and strategies in development. Keywords acyclovir; herpes simplex virus; microbicide; vaccineThe discovery of acyclovir (ACV), a nucleoside analogue that is selectively phosphorylated by herpes simplex virus (HSV) and inhibits viral replication by acting as a substrate for viral DNA polymerase, ushered in a new era in antiviral chemo therapy [1,2]. Despite the overwhelming success of ACV and related drugs, HSV remains a major global health problem, and is the leading cause of encephalitis and genital ulcerative disease, and a major cofactor for HIV infection. This reflects, in part, the ability of the virus to uniformly establish latency, reactivate frequently and to be horizontally and vertically transmitted during periods of

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“…The vaccine was immunogenic and appeared to decrease the severity of recurrent HSV-2 disease (46), but it did not undergo further development. Experience with a preparation emphasizing viral proteins expressed in the cytoplasm of infected cells has been recently updated by Skinner et al (243). The preparation of a recent HSV-1 vaccine involved the reduction of nuclear material by detergent lysis, treatment with formaldehyde, centrifugation to remove virions, and harvest of a protein fraction of the remaining material by acetone precipitation.…”

Section: Fractionated-virus Vaccinesmentioning

confidence: 99%

Recent Progress in Herpes Simplex Virus Immunobiology and Vaccine Research

2003

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Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) cause prevalent, chronic infections that have serious outcomes in some individuals. Neonatal herpes may occur when the infant traverses the cervix during maternal genital herpes. Genital herpes is a major risk factor for human immunodeficiency virus type 1 transmission. Considerable efforts have been made to design and test vaccines for HSV, focusing on genital infection with HSV-2. Several protein subunit vaccines based on HSV-2 envelope glycoproteins have reached advanced-phase clinical trials. These antigens were chosen because they are the targets of neutralizing-antibody responses and because they elicit cellular immunity. Encouraging results have been reported in studies of treatment of HSV-seronegative women with a vaccine consisting of truncated glycoprotein D of HSV-2 and a novel adjuvant. Because most sexual HSV transmission occurs during asymptomatic shedding, it is important to evaluate the impact of vaccination on HSV-2 infection, clinically apparent genital herpes, and HSV shedding among vaccine recipients who acquire infection. There are several other attractive formats, including subunit vaccines that target cellular immune responses, live attenuated virus strains, and mutant strains that undergo incomplete lytic replication. HSV vaccines have also been evaluated for the immunotherapy of established HSV infection

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The efficacy and safety of Skinner herpes simplex vaccine towards modulation of herpes genitalis; report of a prospective double-blind placebo-controlled trial

Cited by 32 publications

References 16 publications

High-Purity Preparation of HSV-2 Vaccine Candidate ACAM529 Is Immunogenic and Efficacious In Vivo

High-Purity Preparation of HSV-2 Vaccine Candidate ACAM529 Is Immunogenic and Efficacious In Vivo

Novel approaches in fighting herpes simplex virus infections

Recent Progress in Herpes Simplex Virus Immunobiology and Vaccine Research

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