BAC-VAC, a novel generation of (DNA) vaccines: A bacterial artificial chromosome (BAC) containing a replication-competent, packaging-defective virus genome induces protective immunity against herpes simplex virus 1. (1/76)

This study aimed to exploit bacterial artificial chromosomes (BAC) as large antigen-capacity DNA vaccines (BAC-VAC) against complex pathogens, such as herpes simplex virus 1 (HSV-1). The 152-kbp HSV-1 genome recently has been cloned as an F-plasmid-based BAC in Escherichia coli (fHSV), which can efficiently produce infectious virus progeny upon transfection into mammalian cells. A safe modification of fHSV, fHSVDeltapac, does not give rise to progeny virus because the signals necessary to package DNA into virions have been excluded. However, in mammalian cells fHSVDeltapac DNA can still replicate, express the HSV-1 genes, cause cytotoxic effects, and produce virus-like particles. Because these functions mimic the lytic cycle of the HSV-1 infection, fHSVDeltapac was expected to stimulate the immune system as efficiently as a modified live virus vaccine. To test this hypothesis, mice were immunized with fHSVDeltapac DNA applied intradermally by gold-particle bombardment, and the immune responses were compared with those induced by infection with disabled infectious single cycle HSV-1. Immunization with either fHSVDeltapac or disabled infectious single cycle HSV-1 induced the priming of HSV-1-specific cytotoxic T cells and the production of virus-specific antibodies and conferred protection against intracerebral injection of wild-type HSV-1 at a dose of 200 LD(50). Protection probably was cell-mediated, as transfer of serum from immunized mice did not protect naive animals. We conclude that BAC-VACs per se, or in combination with genetic elements that support replicative amplification of the DNA in the cell nucleus, represent a useful new generation of DNA-based vaccination strategies for many viral and nonviral antigens.  (+info)

Treatment of common cutaneous herpes simplex virus infections. (2/76)

Herpes simplex virus infection is increasingly common in the United States. New antiviral medications have expanded treatment options for the two most common cutaneous manifestations, orolabial and genital herpes. Acyclovir therapy remains an effective and often less expensive option. Famciclovir and valacyclovir offer improved oral bioavailability and convenient oral dosing schedules but are more expensive than acyclovir. Patients who have six or more recurrences of genital herpes per year can be treated with one of the following regimens: acyclovir, 400 mg twice daily; valacyclovir, 1 g daily; or famciclovir, 250 mg twice daily. These regimens are effective in suppressing 70 to 80 percent of symptomatic recurrences. Episodic treatment of recurrent genital herpes is of questionable benefit, but it may be helpful in appropriately selected patients. There is little evidence indicating benefit from treatment of recurrent orolabial herpes, which tends to be mild and infrequent.  (+info)

Combination treatment with famciclovir and a topical corticosteroid gel versus famciclovir alone for experimental ultraviolet radiation-induced herpes simplex labialis: a pilot study. (3/76)

To investigate the efficacy of corticosteroids for the treatment of herpes labialis, we compared famciclovir (Famvir, 500 mg 3x/day po [per os] for 5 days) and topical fluocinonide (0.05% Lidex Gel 3x/day for 5 days) with famciclovir and topical vehicle control for experimental ultraviolet radiation-induced herpetic recurrences. We irradiated 49 volunteers, and 29 (60%) of 48 developed signs or symptoms of a recurrence. They self-initiated treatment, and we were able to evaluate them. There was a trend in the combination group toward more aborted lesions, compared with those who received antiviral therapy alone (7 [41%] of 17 vs. 1 [8%] of 12; P=.09). Combination therapy significantly reduced the median maximum lesion size (48 vs. 162 mm(2); P=.02) and the number of patients who experienced lesion pain (10 [59%] of 17 vs. 12 [100%] of 12; P=.02). Adverse events were minimal. Corticosteroids in combination with an antiviral agent may be safe and beneficial for episodic treatment of herpes labialis. Larger studies are needed to confirm these findings.  (+info)

Effects of antiviral usage on transmission dynamics of herpes simplex virus type 1 and on antiviral resistance: predictions of mathematical models. (4/76)

Herpes simplex virus type 1 (HSV-1) causes recurrent herpes labialis (RHL), a common disease afflicting up to 40% of adults worldwide. Mathematical models are used to analyze the effect of antiviral treatment on the transmission of, and the prevalence of drug resistance in, HSV-1 in the United States. Three scenarios are analyzed: no antiviral use, the current level of use, and a substantial increase in nucleoside analogue use, such as might occur if topical penciclovir were available over-the-counter for the treatment of RHL. A basic model predicts that present level of nucleoside analogue use has a negligible effect on HSV-1 transmission and that even if use of topical penciclovir for (RHL) increased substantially, the overall prevalence of infectious HSV-1 is unlikely to be reduced by more than 5%. An expanded model, which allows for acquired resistance and includes immunocompromised hosts and other more realistic features, predicts that current antiviral use is unlikely to lead to any noticeable increase in resistance. If antiviral use increases, the resulting rise in resistance in the population will depend primarily on the probability that immunocompetent hosts will acquire permanent resistance upon treatment. This probability is known to be small, but its exact value remains uncertain. If acquired resistance occurs less than once per 2,500 treated episodes, then in the community at large, the frequency of HSV-1 resistance is predicted to increase slowly, if at all (remaining below 0.5% for >50 years), even with extensive nucleoside analogue use. If acquired resistance emerges in 1 of 625 treated episodes (the maximum of an approximate 95% confidence interval derived from the results of several studies of resistance in treated hosts), then the prevalence of infection with resistant HSV-1 could rise from about 0.2% to 1.5 to 3% within 50 years. The limitations of existing data on acquired resistance and the potential impact of acquired resistance if it occurs are discussed, and strategies are suggested for enhancing information on acquired resistance. The predictions of this model contrast with the more rapid increases in antimicrobial resistance anticipated by models and observed for other pathogenic bacteria and viruses. The reasons for these contrasting predictions are discussed.  (+info)

Enhancement of the eighth cranial nerve and labyrinth on MR imaging in sudden sensorineural hearing loss associated with human herpesvirus 1 infection: case report. (5/76)

The case of a 61-year-old woman who presented with herpes labialis, subclinical meningitis, and sudden onset of bilateral sensorineural hearing loss is presented. Contrast-enhanced MR imaging showed marked bilateral enhancement of the intracanalicular portion of the eighth cranial nerve, right cochlea, and left vestibule. Polymerase chain reaction was positive for human herpesvirus 1 obtained from the cerebral spinal fluid, which suggested the diagnosis of viral neuritis.  (+info)

Prevalence of recurrent herpes labialis and aphthous ulcers among young adults on six continents. (6/76)

The prevalence of recurrent herpes labialis (RHL) and recurrent aphthous ulcers (RAU) in young adults - - 635 armed-forces recruits and 9897 health-profession students - - in 48 institutions in 21 countries was determined by a questionnaire survey. Two or more occurrences (lifetime prevalence) of RHL were reported by 33.2% of men and 28.0% of women; the corresponding figures for RAU were 38.7% and 49.7%. North American respondents, mainly from Canada, had a significantly higher prevalence of both lesions. There were some differences in relation to profession. Approximately 15% of all the people surveyed had had herpes labialis and 25% had had aphthous ulcers at least once during the previous year. Persons with a history of recurrence of one lesion were more likely to have a history of recurrence of the other.  (+info)

Double-blind, randomized, placebo-controlled study of topical 5% acyclovir-1% hydrocortisone cream (ME-609) for treatment of UV radiation-induced herpes labialis. (7/76)

Immunopathology is recognized as an important component of infectious disease manifestations, and corticosteroids have been used as an adjunct to antimicrobial therapy for a variety of conditions. Antiviral therapy of herpes labialis has been shown to result in only a small reduction in the time to healing and the duration of pain. To determine if topical application of a combination product containing 5% acyclovir and 1% hydrocortisone (ME-609) could provide benefit to herpes labialis patients, 380 immunocompetent adults with a history of herpes labialis were exposed to experimental UV radiation (UVR) to induce a recurrence. On day 2, just before the appearance of the majority of lesions ("delayed" lesions), subjects were randomized to receive active medication or vehicle control six times per day for 5 days. Overall, 120 of 380 patients developed delayed classical lesions, of whom 50 of 190 (26%) had been treated with ME-609 and 70 of 190 (37%) had received placebo (a reduction of 29% [P = 0.02]). Healing time, measured as the time to normal skin, was reduced by treatment with ME-609 (9.0 days for treated patients versus 10.1 days for the controls [P = 0.04]). There was a trend toward a reduction in the maximum lesion size in the ME-609 recipients compared to that in the controls (43 versus 60 mm(2), respectively [P = 0.07]). The treatment had no effect on lesion pain, but ME-609 treatment reduced the number of patients with moderate or severe tenderness. Compared to treatment with a placebo, treatment with the combination antiviral-immunomodulatory cream provided benefit to patients with experimental UVR-induced herpes labialis, reducing classical lesion incidence, healing time, lesion size, and lesion tenderness. ME-609 is a novel product that merits further evaluation as a treatment for cold sores.  (+info)

Acyclovir cream for treatment of herpes simplex labialis: results of two randomized, double-blind, vehicle-controlled, multicenter clinical trials. (8/76)

Acyclovir cream has been available for the treatment of herpes labialis in numerous countries outside the United States for over a decade. Evidence for its efficacy comes from a few small clinical trials conducted in the 1980s. To examine more comprehensively the efficacy and safety of this formulation, we conducted two independent, identical, parallel, randomized, double-blind, vehicle-controlled, large-scale multicenter clinical trials. Healthy adults with a history of frequent herpes labialis were recruited from the general population, screened for eligibility, randomized equally to 5% acyclovir cream or vehicle control, given study medication, and told to self-initiate treatment five times daily for 4 days beginning within 1 h of the onset of a recurrent episode. The number of patients who treated a lesion was 686 in study 1 and 699 in study 2. In study 1, the mean duration of episodes was 4.3 days for patients treated with acyclovir cream and 4.8 days for those treated with the vehicle control (hazards ratio [HR] = 1.23; 95% confidence interval [CI], 1.06 to 1.44; P = 0.007). In study 2, the mean duration of episodes was 4.6 days for patients treated with acyclovir cream and 5.2 days for those treated with the vehicle control (HR = 1.24; 95% CI, 1.06 to 1.44; P = 0.006). Efficacy was apparent whether therapy was initiated "early" (prodrome or erythema lesion stage) or "late" (papule or vesicle stage). There was a statistically significant reduction in the duration of lesion pain in both studies. Acyclovir cream did not prevent the development of classical lesions (progression to vesicles, ulcers, and/or crusts). Adverse events were mild and infrequent.  (+info)