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L R Stanberry

Publications and source records attributed to L R Stanberry.

At least 37 records · Page 2Linked to original sources
PubMed1999

Herpes simplex virus vaccines.

Herpes simplex virus (HSV) infections are common and produce not only a primary infection, but also latent and recurrent infections. Therefore, the goals of a HSV vaccine are different from other vaccines. In this review, the goals of both prophylactic and therapeutic HSV vaccines are discussed and related to the immunobiology of acute and recurrent HSV infections. Next, the vaccine strategies that have been and are being evaluated for control of HSV disease are described. Current approaches take advantage of many of the modern methodologies for vaccine development. Thus, as we await final evaluations of subunit HSV glycoprotein vaccines, early phase I trails are evaluating newer vaccine approaches including DNA-based vaccines and replication-impaired viruses. The definitive HSV vaccine may await increased knowledge of the optimal viral antigen(s) and routes to induce genital tract immunity.

Animals↗
PubMed1999

Effect of undecylenic acid as a topical microbicide against genital herpes infection in mice and guinea pigs.

There is increasing interest in the use of topical microbicides to help prevent the spread of sexually transmitted diseases (STD). Undecylenic acid (UA), a monosaturated fatty acid, is the active ingredient in a number of over-the-counter (OTC) antifungal spray powders, that also exhibits in vitro antibacterial and antiviral activity, including herpes simplex virus (HSV) activity. We, therefore, evaluated UA as a topical microbicide against genital HSV infection using the murine and guinea pig models of genital herpes. Mice were administered a 20% solution of UA in polyethylene glycol (PEG) vehicle, vehicle alone or phosphate buffered saline (PBS) intravaginally immediately prior to vaginal challenge with HSV-2. Pre-treatment with UA decreased the number of mice that became infected (P < 0.001 vs. PBS or vehicle control), developed symptoms (P <0.001) or died (P <0.001). However, when treatment was extended to either 5 min prior to or after viral inoculation, protection was lost. Similar findings were found using the guinea pig model, where UA treatment completely prevented HSV-2 vaginal infection when given immediately prior to HSV-2 inoculation (P<0.001 vs. PBS or vehicle control). Thus, UA, an approved OTC medication, provided significant protection against HSV disease and infection only when applied immediately before viral inoculation, indicating that better formulations were needed to extend the duration of protection.

Administration, Topical↗
PubMed1999

Plant products as topical microbicide candidates: assessment of in vitro and in vivo activity against herpes simplex virus type 2.

There is considerable interest in developing topical microbicides; products to be used intravaginally by women for protection against sexually transmitted diseases. Many compounds derived from plants have been shown to have antimicrobial properties. We examined 19 such compounds in vitro by plaque reduction assay to determine their activity against a common sexually transmitted pathogen, herpes simplex virus type 2. Compounds with an ED50 < or = 7.0 mg/ml were tested for efficacy in vivo. Four compounds, carrageenan lambda type IV, cineole, curcumin, and eugenol, provided significant protection (P < 0.05) in a mouse model of intravaginal HSV-2 challenge. Eugenol, which provided the greatest protection in mice was also evaluated using the guinea pig model of genital HSV-2 infection where it also demonstrated significant protection. Based on these results, several plant-derived compounds appear to warrant further evaluation as potential microbicides.

Animals↗
PubMed1999

The topical microbicide PRO 2000 protects against genital herpes infection in a mouse model.

Vaginal gel formulations containing the naphthalene sulfonate polymer PRO 2000 are being developed as topical microbicides to protect against infection with sexually transmitted disease (STD) pathogens. A mouse model was used to determine whether PRO 2000 could protect against genital herpes in vivo. Animals received a single intravaginal application of 15 microL of a 10% PRO 2000 aqueous solution or a 4.0% or 0.5% PRO 2000 vaginal gel formulation 20 s prior to intravaginal challenge with 4.0 log10 pfu of herpes simplex virus type 2. Treatment with the 4.0% gel provided complete protection against infection; treatment with the 0.5% gel or 10% solution provided 81% and 80% protection, respectively. Furthermore, the 4% gel provided significant protection even when viral challenge was delayed until 60 min after treatment. This is the first report to show that PRO 2000 can protect against infection with an STD pathogen in vivo.

Administration, Topical↗
PubMed1999

A temporal analysis of acyclovir inhibition of induced herpes simplex virus type 1 In vivo reactivation in the mouse trigeminal ganglia.

It is generally assumed that reactivation of latent herpes simplex virus occurs through initiation of lytic viral gene transcription from the latent viral genome. Thus, antiviral compounds such as acyclovir, whose activation is dependent upon viral thymidine kinase, should be effective in preventing the initial production of infectious virus associated with reactivation. To test this concept, the ability of acyclovir to prevent the production of infectious virus was determined in the murine hyperthermic stress (HS) model of in vivo reactivation. Acyclovir treatment after HS blocked the production of infectious virus within the ganglia. Efficacy was dependent upon the timing of the first post-HS dose and the length of exposure to acyclovir. A single dose administered 6-9 h after HS resulted in >90% reduction in reactivation. Acyclovir administered 12 h after HS resulted in 75% reduction, but there was no effect if treatment was delayed for 18 h after HS.

Acyclovir↗
PubMed1999

College students' attitudes regarding vaccination to prevent genital herpes.

BACKGROUND AND OBJECTIVES: Vaccines represent an important strategy for the control of infectious diseases but are only effective if accepted by the public. Unique attitudinal issues may affect usage of vaccines to control sexually transmitted diseases (STDs). The object of this study was to examine among college students factors that may influence acceptance of a vaccine against genital herpes. GOALS: To examine attitudes regarding acceptance of vaccination for genital herpes by college students using aspects of health behavior theories. STUDY DESIGN: Subjects were recruited from an undergraduate psychology class to complete a questionnaire regarding attitudes and beliefs about receiving a potential genital herpes vaccine. RESULTS: Of the 518 subjects, 100 would not get the vaccine, 207 would, and 211 were unsure. In the final models, factors that influenced acceptance were low cost and an opinion that the vaccine should be recommended for everyone. Those who were unsure were more likely to be influenced by an opinion that the vaccine would be unsuccessful. While not remaining in the final models, those who believed they were at low risk of acquiring genital herpes were unlikely to accept a genital herpes vaccine. CONCLUSIONS: Our results indicate that most college students would not reject vaccination, a priori, against genital herpes. Vaccine acceptance may be maximized if vaccine cost is low, the public is educated regarding risk of acquiring genital herpes, and public health policy encourages universal vaccination.

Adolescent↗
PubMed1999

Locus of control for general health and STD acquisition among adolescent girls.

PURPOSE: To examine adolescent girls' perception of control over general health and sexually transmitted disease (STD) acquisition. METHODS: Adolescents participating in a longitudinal study were asked questions regarding their perception of their locus of control. These questions, adopted from a previous measure, focused on six loci: internal control, control by parents, partners, peers, and health care providers, and chance. RESULTS: There were 128 girls (mean age, 17 years; range, 14.5 to 18.8); 82% were black and 18% white. Statistically significant associations were found between control of general health and STD acquisition for each locus of control subscale, with the exception of partner control. However, the girls reported significantly less control over STD acquisition than over general health for health care providers, parents, and by chance, and significantly more partner and internal control over STD acquisition than general health. The correlations between parental control over general health and over STD acquisition were inversely correlated with age. Partner control was positively related to current condom use, but internal control was not. CONCLUSIONS: The degree of the locus of control was specific for STD acquisition. Girls who believe they should be able to control STD acquisition may not be using condoms. The view of partners as having control over STD acquisition may represent joint communication or coercion. However, in general these findings support the development of female-controlled methods for STD prevention, such as topical microbicides.

Adolescent↗
PubMed1999

Civamide (cis-capsaicin) for treatment of primary or recurrent experimental genital herpes.

Neuropharmacologic agents able to disrupt normal virus-neuron interactions may provide an alternative strategy for the treatment of herpes simplex virus (HSV) infections. We have previously shown that prophylactic treatment with capsaicin, a natural compound that alters function in sensory neurons, can protect guinea pigs against cutaneous HSV disease, even though the compound has no direct antiviral activity. Here we have examined the ability of civamide, the cis isomer of capsaicin, to interfere with HSV disease. We show that, even when the onset of treatment was delayed until after intravaginal virus challenge, primary genital skin disease severity was significantly reduced. In addition, animals treated during primary infection subsequently experienced a long-lasting reduction in recurrent disease. Civamide treatment during latent infection also significantly reduced recurrent disease, although for a shorter period. Further a single weekly treatment with civamide during latent infection was sufficient to reduce recurrent disease, indicating that an infrequent suppressive maintenance therapy might be possible.

Administration, Topical↗
PubMed1999

College students' knowledge and perceptions of genital herpes.

Given the rising prevalence of herpes simplex virus type 2 (HSV-2) and the lack of accurate information about STDs in general, it is important to understand specific aspects of knowledge and attitudes regarding genital herpes acquisition among college students. This study examined the knowledge and attitudes regarding HSV-2 among college students by recruiting subjects (n=518) from an undergraduate psychology class to complete a questionnaire. The percentage of students answering individual knowledge items correctly ranged from 67% to 99%. The media was a common source of information, and almost one-third of the students anticipated that their care provider would think negatively of them should they acquire the disease. There were gender differences in care-seeking behaviour, knowledge, and attitudes, with females having a more negative view of themselves if they acquired the disease. This study pointed to the challenges in ensuring accurate knowledge about genital herpes that will encourage preventive behaviours without causing undue alarm or shame.

Adult↗
PubMed1999

Seroprevalence of herpes simplex virus-type 2 in African-American college women.

This study examines the relationship between sexual behaviors and prevalence of herpes simplex virus-type 2 (HSV-2) among African-American college women. Subjects (n = 138) were recruited randomly from a state university to participate in a study regarding sexual attitudes and behaviors and to have their blood drawn for type-specific HSV seroprevalence. Sera were analyzed for 96 college women with a mean age of 21 years. Of the 96 women, 29 (30%) were HSV-2 seropositive. The results of this study revealed that a history of sexually transmitted disease was predictive of HSV-2 infection. Number of lifetime partners, however, was not related to HSV-2 seropositivity. Four (31%) of the 13 women who reported only one lifetime partner were seropositive. These findings indicate that for young African-American college women, the risk of being infected with HSV-2 is high even with only one lifetime partner. Behavioral strategies focused on decreasing the number of sexual partners are not likely to be sufficient in preventing the spread of HSV-2 infection among young African-American women. The development and use of alternative approaches to prevent the spread of HSV-2 among young African Americans should be considered.

Adolescent↗
PubMed1998

Herpes. Vaccines for HSV.

Herpes simplex viruses type 1 (HSV-1) and 2 (HSV-2) are ubiquitous human pathogens capable of producing primary, latent, and recurrent infections. These viruses cause a variety of clinical illnesses including genital herpes, oral-facial infections, cutaneous infections, ocular infections, neonatal herpes, herpes encephalitis, disseminated infection, and erythema multiforme. This article summarizes the past and current efforts to develop both prophylactic and therapeutic HSV vaccines.

Encephalitis, Viral↗
PubMed1998

Topical microbicides. Current status and research considerations for adolescent girls.

BACKGROUND AND OBJECTIVES: For sexually active adolescent girls, sexually transmitted diseases (STDs) represent a significant health problem. Although condom use may be an effective intervention against STDs in this high-risk population, actual use depends on the cooperation of the male partner. Therefore, the development of female-controlled methods such as topical microbicides have been endorsed as an important option for STD prevention. GOALS: This article reviews the current status of intravaginal microbicide development and discusses aspects of adolescent development that should be considered in topical microbicide research. RESULTS: Biological development, cognitive capacities, psychosexual maturation, and the sociocultural context are key features that affect the likelihood that adolescents will adopt microbicides as a specific methods of STD protection. CONCLUSION: Adoption of topical microbicides by adolescents will require an "adolescent friendly" perspective for topical microbicides to have a significant impact on the STD epidemic.

Administration, Topical↗
PubMed1998

Control of STDs--the role of prophylactic vaccines against herpes simplex virus.

OBJECTIVES: To summarise the current status of genital herpes simplex virus (HSV) vaccine development and provide a discussion of the potential benefits and limitations of genital herpes vaccines. METHODS: Literature review. RESULTS: Genital herpes simplex virus infection has a complex pathogenesis that has contributed to it becoming a serious worldwide problem. In an attempt to control the problem five different types of genital herpes vaccines have been developed. These include inactivated virion derived vaccines, adjuvanted subunit vaccines, vectored vaccines, replication limited live viral vaccines, genetically attenuated live viral vaccines, and nucleic acid vaccines. While available commercially in some parts of the world, inactivated virion derived vaccines have not been proved effective. Of the others, adjuvanted subunit vaccines, replication limited live viral vaccines, and nucleic acid vaccines are currently in clinical trials and vectored vaccines and genetically attenuated live viral vaccines are in preclinical development. CONCLUSION: With regard to HSV vaccines in general, it is reasonable to expect that the newer vaccines may protect the individual from developing symptomatic genital herpes but may not protect against asymptomatic viral infection. With widespread use HSV vaccines might help to prevent the spread of genital herpes.

Herpes Genitalis↗
PubMed1997

Construction and characterization of a replication-defective herpes simplex virus 2 ICP8 mutant strain and its use in immunization studies in a guinea pig model of genital disease.

A replication-defective mutant of herpes simplex virus 2 (HSV-2) was engineered by replacing the ICP8 gene of HSV-2 strain 186 with an ICP8-lacZ fusion gene from the herpes simplex virus 1 (HSV-1) HD-2 mutant strain. The resulting virus, HSV-2 5BlacZ, is defective for growth in Vero cells but is capable of growth in a cell line that expresses HSV-1 ICP8. In Vero cells, the mutant virus is defective for DNA synthesis but is able to express many viral proteins at levels similar to those of wild-type virus, including several of the late kinetic class. SDS-PAGE and Western blot analysis demonstrated the expression of glycoproteins B and D by 5BlacZ in Vero cells. Initial studies have shown that immunization with 5BlacZ protects guinea pigs from intravaginal HSV-2 challenge. Immunized animals had less severe genital skin disease and reduced replication of the challenge virus in the genital tract during primary infection and reduced episodes of recurrent disease. Thus, HSV-2 ICP8 shows gene regulatory properties similar to those of HSV-1 ICP8, and this HSV-2 ICP8 mutant virus shows a phenotype similar to those of HSV-1 ICP8 mutant strains. Replication-defective mutants of HSV-2 offer a potential vaccine approach for immune intervention against HSV-2 genital disease and latent infection.

Animals↗
PubMed1997

Seroprevalence of herpes simplex virus types 1 and 2 and cytomegalovirus in adolescents.

We determined the prevalence of herpes simplex virus (HSV) and cytomegalovirus (CMV) antibodies in a cohort of adolescents 12 to 22 years of age in anticipation of the development of vaccines to control HSV and CMV infections. For the overall study population, we found that 62% were seropositive for HSV type 1 (HSV-1), 12% were seropositive for HSV type 2 (HSV-2), and 65% were seropositive for CMV. Race was not related to HSV-1 seropositivity, but African-American adolescents were more likely than Caucasian adolescents to be seropositive for HSV-2 and CMV. Girls also were more likely than boys to be seropositive for HSV-2 and CMV. For boys, history of a sexually transmitted disease was identified as a risk factor for HSV-2 seropositivity; for girls, a greater number of sexual partners increased the risk of being seropositive for HSV-2. Our data demonstrating a high prevalence of infection during adolescence suggest that immunization for HSV-1, HSV-2, and CMV may need to occur in childhood.

Adolescent↗
PubMed1997

Impact of demographics, sexual history, and psychological functioning on the acquisition of STDS in adolescents.

Sexually transmitted diseases (STDs) are associated with significant morbidities for adolescents. This study sought to determine the relationship of demographic characteristics, sexual history, and psychological characteristics to actual acquisition of STD. Adolescents were recruited from their source of primary care: 44 males and 88 females matched on age and race. A series of logistic regression analyses were used to determine which of the independent variables were significantly associated with self-reported STD occurrences. When age, race, and gender were pretested, older age and being female were found to be associated with more episodes. The final model consisted of older age, female gender, greater number of lifetime partners, perceived greater frequency of STDs among adolescents in general, less negative feelings about STD acquisition, and being less likely to believe your friends would think you were bad. The findings indicate that acquisition of an STD is related to the demographic characteristics of age and gender, as well as to the number of lifetime partners and attitudes about STD acquisition. This information can be used to develop intervention programs.

Adolescent↗
PubMed1996

The characteristic site-specific reactivation phenotypes of HSV-1 and HSV-2 depend upon the latency-associated transcript region.

After replication at sites of initial inoculation, herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) establish lifelong latent infections of the sensory and autonomic neurons of the ganglia serving those sites. Periodically, the virus reactivates from these neurons, and travels centripetally along the neuronal axon to cause recurrent epithelial infection. The major clinically observed difference between infections with herpes simplex virus type 1 and type 2 is the anatomic site specificity of recurrence. HSV-1 reactivates most efficiently and frequently from trigeminal ganglia, causing recurrent ocular and oral-facial lesions, while HSV-2 reactivates primarily from sacral ganglia causing recurrent genital lesions. An intertypic recombinant virus was constructed and evaluated in animal models of recurrent ocular and genital herpes. Substitution of a 2.8-kbp region from the HSV-1 latency-associated transcript (LAT) for native HSV-2 sequences caused HSV-2 to reactivate with an HSV-1 phenotype in both animal models. The HSV-2 phenotype was restored by replacing the mutated sequences with wild-type HSV-2 LAT-region sequences. These sequences or their products must act specifically in the cellular environments of trigeminal and sacral neurons to promote the reactivation patterns characteristic of each virus.

Animals↗