Genital Herpes Simplex Virus Type Research Articles

Seroprevalence of Herpes Simplex Virus Type 1 and 2 Among Pregnant Women, 1989–2010

Genital herpes in pregnancy frequently complicates management, although neonatal herpes, a potentially catastrophic complication, is rare1,2. Maternal acquisition of genital herpes simplex virus (HSV) type 1 or 2 near the time of delivery accounts for most neonatal herpes. Neonatal HSV incidence has been stable in recent decades, although a shift toward more HSV-1 infections has been reported1,3. Concurrently, a decline in HSV-1 seroprevalence, but not HSV-2, has been noted among reproductive-aged women in nationwide surveys4,5. We determined trends in the seroprevalence of HSV-1 and HSV-2 among pregnant women delivering in a single urban academic center during two decades in Seattle, Washington.

Psychological distress, emotional stability, and emotion regulation moderate dynamics of herpes simplex virus type 2 recurrence.

Herpes simplex virus type 2 (HSV-2) genital lesion recurrence is modulated by psychological factors, but no such link with viral shedding (and thus asymptomatic transmission) has been observed in humans. The moderating effects of average psychological distress, emotional stability, and emotion regulation on HSV-2 recurrence were tested. Nineteen HSV-2 seropositive women were followed over 22weeks. Daily measures of HSV-2 recurrence and psychological distress were collected. HSV-2 lesions and viral shedding were modeled as linear oscillator systems, with psychological distress moderating the periodicity of each process. High levels of distress, more labile moods, and less ability to regulate emotional states were associated with fewer days elapsed between the onset of lesion episodes. Viral shedding showed the same pattern. Results are consistent with research indicating that psychological distress suppresses immune system functioning, and provide new evidence that genital HSV-2 viral shedding is related to, and regulated by, psychological distress.

Topical SMIP-7.7, a Toll–Like Receptor 7 Agonist, Protects against Genital Herpes Simplex Virus Type-2 Disease in the Guinea Pig Model of Genital Herpes

Development of more effective therapies for genital herpes simplex virus type-2 (HSV-2) infections remains a priority. The toll-like receptors (TLR) are attractive targets for the immunomodulation of primary and recurrent genital herpes infection. The guinea pig model of genital HSV-2 disease was therefore used to evaluate the efficacy of a new TLR-7 agonist, SMIP-7.7. The effects of SMIP-7.7 at concentrations between 0.90% and 0.09% were compared to the vehicle control or Aldara(®) (3M Health Care Limited, Northridge, CA, USA) as treatment for genital HSV-2 infections. Following intravaginal inoculation of Hartley guinea pigs with 10(6) pfu HSV-2 (MS strain), animals were treated intravaginally beginning at 36 h post-infection. Animals were evaluated for acute disease, acute virus replication, recurrent disease and shedding, as well as infection of the dorsal root ganglia. Treatment with SMIP-7.7 significantly decreased mean total lesion scores during primary infection (all doses, P<0.01 compared with vehicle control, and similar to Aldara(®)). Vaginal virus titres were reduced in treated animals compared with vehicle control (P<0.001 for each treatment versus vehicle control on day 4). Treatment with SMIP-7.7 also significantly decreased the number of recurrent lesion days, the number of days with recurrent virus shedding and the infection of the dorsal root ganglia compared to the vehicle control, and was similar to Aldara(®). As opposed to Aldara(®), SMIP-7.7 did not induce fever or weight loss during treatment. SMIP-7.7 improves the outcome of primary and recurrent HSV-2 disease comparable to Aldara(®) but without some of the side effects associated with Aldara(®).

Association of Tenofovir (TFV) Detection with Reduced Risk of Herpes Simplex virus Type-2 (HSV-2) Acquisition in the VOICE (MTN 003) Study

AIDS Research and Human RetrovirusesVol. 30, No. S1 Bacterial Vaginosis and HSV-2: Impact on Genital ImmunityAssociation of Tenofovir (TFV) Detection with Reduced Risk of Herpes Simplex virus Type-2 (HSV-2) Acquisition in the VOICE (MTN 003) StudyJeanne Marrazzo, Lorna Rabe, Cliff Kelly, Edward Livant, Z. Mike Chirenje, Barbra Richardson, James Dai, Jeanna Piper, Sharon Hillier, and the VOICE Study TeamJeanne MarrazzoUniversity of Washington, Seattle, WA, United StatesSearch for more papers by this author, Lorna RabeMagee Women Research Institute, Pittsburgh, PA, United StatesSearch for more papers by this author, Cliff KellySCHARP - FHCRC, Seattle, WA, United StatesSearch for more papers by this author, Edward LivantMagee Women Research Institute, Pittsburgh, PA, United StatesSearch for more papers by this author, Z. Mike ChirenjeUniversity of California San Francisco Research Programme, Harare, ZimbabweSearch for more papers by this author, Barbra RichardsonSCHARP - FHCRC, Seattle, WA, United StatesSearch for more papers by this author, James DaiSCHARP - FHCRC, Seattle, WA, United StatesSearch for more papers by this author, Jeanna PiperDAIDS, NIAID, NIH, Bethesda, MD, United StatesSearch for more papers by this author, Sharon HillierMagee Women Research Institute, Pittsburgh, PA, United StatesSearch for more papers by this author, and the VOICE Study TeamSearch for more papers by this authorPublished Online:30 Oct 2014https://doi.org/10.1089/aid.2014.5047a.abstractAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Association of Tenofovir (TFV) Detection with Reduced Risk of Herpes Simplex virus Type-2 (HSV-2) Acquisition in the VOICE (MTN 003) Study." AIDS Research and Human Retroviruses, 30(S1), p. A31FiguresReferencesRelatedDetailsCited byA randomized safety and pharmacokinetic trial of daily tenofovir 1% gel in term and near-term pregnancy21 September 2016 | Journal of the International AIDS Society, Vol. 19, No. 1Oral and Vaginal Tenofovir for Genital Herpes Simplex Virus Type 2 Shedding in Immunocompetent Women: A Double-Blind, Randomized, Cross-over Trial4 June 2015 | Journal of Infectious Diseases, Vol. 212, No. 12 Volume 30Issue S1Oct 2014 InformationCopyright 2014, Mary Ann Liebert, Inc.To cite this article:Jeanne Marrazzo, Lorna Rabe, Cliff Kelly, Edward Livant, Z. Mike Chirenje, Barbra Richardson, James Dai, Jeanna Piper, Sharon Hillier, and the VOICE Study Team.Association of Tenofovir (TFV) Detection with Reduced Risk of Herpes Simplex virus Type-2 (HSV-2) Acquisition in the VOICE (MTN 003) Study.AIDS Research and Human Retroviruses.Oct 2014.A31-A31.http://doi.org/10.1089/aid.2014.5047a.abstractPublished in Volume: 30 Issue S1: October 30, 2014PDF download

Seroprevalence of herpes simplex virus type 1 and 2 among pregnant women, 1989-2010.

Genital herpes in pregnancy frequently complicates management, although neonatal herpes, a potentially catastrophic complication, is rare1,2. Maternal acquisition of genital herpes simplex virus (HSV) type 1 or 2 near the time of delivery accounts for most neonatal herpes. Neonatal HSV incidence has been stable in recent decades, although a shift toward more HSV-1 infections has been reported1,3. Concurrently, a decline in HSV-1 seroprevalence, but not HSV-2, has been noted among reproductive-aged women in nationwide surveys4,5. We determined trends in the seroprevalence of HSV-1 and HSV-2 among pregnant women delivering in a single urban academic center during two decades in Seattle, Washington.

Epidemiology of Genital Herpes Simplex Virus Type 1 and 2 Infections in Southwestern Finland During a 10-Year Period (2003–2012)

The objective of this study was to analyze the proportion of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) in genital infections during a 10-year period (2003-2012) among outpatients of a clinic of sexually transmitted disease in Southwestern Finland. We analyzed prospectively the proportion of HSV-1- or HSV-2-positive culture samples from our sexually transmitted disease clinic outpatients with genital herpes infection during the years 2003 to 2012 and compared the proportions of positive HSV-1 and HSV-2 findings with the age and sex of the patients. Herpes simplex virus type 2 was typed in 66.4% (557/839) and HSV-1 in 33.6% (282/839) of the patients during the entire study period. The mean age of male patients (26.3 years) with a laboratory-confirmed HSV-1 infection was significantly lower than that in male patients with an HSV-2 infection in 2003 to 2007 (26.3 vs. 32.9 years), with P < 0.0001, and (28.6 vs. 34.0) P < 0.0019 in 2008 to 2012, respectively. More female than male patients had HSV-1 infection; in the first study period (2003-2007), 58% were female, and in 2008 to 2012, it was again 63.6%. There was no significant difference between the age of female patients with HSV-1 and those with HSV-2. Herpes simplex virus type 2 was still the most common causative agent of genital herpes in Southwestern Finland, but the proportion of HSV-1 was increasingly high. The age difference between male patients with HSV-1 and HSV-2 narrowed during the years studied.

Better Neutralization of Herpes Simplex Virus Type 1 (HSV-1) Than HSV-2 by Antibody From Recipients of GlaxoSmithKline HSV-2 Glycoprotein D2 Subunit Vaccine

The Herpevac Trial evaluated a herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit vaccine to prevent genital herpes. Unexpectedly, the vaccine protected against genital HSV-1 infection but not genital HSV-2 infection. We evaluated sera from 30 women seronegative for HSV-1 and HSV-2 who were immunized with gD2 in the Herpevac Trial. Neutralizing antibody titers to HSV-1 were 3.5-fold higher than those to HSV-2 (P < .001). HSV-2 gC2 and gE2 on the virus blocked neutralization by gD2 antibody, while HSV-1 gC1 and gE1 did not block neutralization by gD2 antibody. The higher neutralizing antibody titers to HSV-1 offer an explanation for the Herpevac results, and shielding neutralizing domains provides a potential mechanism.

Recurrent Herpes Simplex Virus Type-2 Meningitis in an Adolescent Girl

【Herpes simplex virus type 2 (HSV2) meningitis primarily develops during or following a primary genital HSV2 infection that was acquired from sexual contact or through the birth canal during delivery from mother. We describe a 15 year old virgin without history of previous herpes simplex infection who developed 2 episodes of HSV2 meningitis. Although recurrent meningitis due to HSV is primarily seen in young or sexually active adults. HSV2 meningitis should be in the differential diagnosis of recurrent meningitis in adolescent patients.】

Incident Herpes Simplex Virus Type 2 Infection Increases the Risk of Subsequent Episodes of Bacterial Vaginosis

Herpes simplex virus type 2 (HSV-2) infected women have a higher prevalence of bacterial vaginosis (BV) compared to HSV-2-seronegative women. To explore the temporal association between these conditions, we evaluated the frequency of BV episodes before and after HSV-2 acquisition in a prospective study of 406 HSV-2/HIV-1-seronegative Kenyan women, of whom 164 acquired HSV-2. Incident HSV-2 was associated with increased likelihood of BV (adjusted OR, 1.28; 95% CI, 1.05-1.56; P = .01). Our findings strengthen the evidence for a causal link between genital HSV-2 infection and disruption of the vaginal microbiota.

Trends in Seroprevalence of Herpes Simplex Virus Type 2 Among Non-Hispanic Blacks and Non-Hispanic Whites Aged 14 to 49 Years—United States, 1988 to 2010

Genital herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually transmitted infections in the United States. We sought to assess differences in HSV-2 seroprevalence among non-Hispanic blacks and non-Hispanic whites and describe trends over time from 1988 to 2010. Data from National Health and Nutrition Examination Surveys (NHANES) were used to determine national HSV-2 seroprevalence estimates from National Health and Nutrition Examination Surveys 1988 to 1994, 1999 to 2002, 2003 to 2006, and 2007 to 2010. Persons aged 14 to 49 years were included in the analyses. Race/Ethnicity was defined by self-report as non-Hispanic white or non-Hispanic black. Purified glycoprotein specific for HSV-2 was used to detect type-specific antibodies using an immunodot assay. The same assay was used in all surveys. History of diagnosed genital herpes was self-reported. Overall, HSV-2 seroprevalence decreased in the United States between 1988 to 1994 and 2007 to 2010, from 21.2% to 15.5%. Among non-Hispanic white females, HSV-2 seroprevalence decreased from 19.5% (1988-1994) to 15.3% (2007-2010; P < 0.001); HSV-2 seroprevalence remained stable among non-Hispanic black females, 52.5% (1988-1994) to 49.9% (2007-2010; P = 0.1). The female black/white prevalence ratio was 2.7 (95% confidence interval [CI], 2.4-3.0) in 1988 to 1994 increasing to 3.3 (95% CI, 2.9-3.7) in 2007 to 2010 (P = 0.01). Among males, the black/white prevalence ratio was 2.4 (95% CI, 1.9-2.9) in 1988 to 1994 increasing to 4.4 (95% CI, 3.3-5.8) in 2007 to 2010 (P = 0.001). The overall percentage of HSV-2-seropositive survey participants who reported never being told by a doctor or health care professional that they had genital herpes did not change significantly between 1988 to 1994 and 2007 to 2010 and remained high (90.7% and 87.4%, respectively). Although HSV-2 seroprevalence decreased overall, the decrease was most marked among non-Hispanic whites, and racial disparities significantly increased over time. These persistent disparities demonstrate the need for innovative prevention strategies among this at-risk population.

Herpes simplex virus type 2 and HIV disease progression: a systematic review of observational studies

BackgroundHerpes simplex virus type 2 (HSV-2) is a common co-infection among HIV-infected adults that is hypothesized to accelerate HIV disease progression.MethodsWe searched Medline, EMBASE, relevant conference proceedings (2006–12) and bibliographies of identified studies without language restriction for cohort studies examining the impact of HSV-2 on highly active antiretroviral therapy-untreated HIV disease in adults. The exposure of interest was HSV-2 seropositivity or clinical/laboratory markers of HSV-2 activity. The primary outcome was HIV disease progression, defined as antiretroviral initiation, development of AIDS/opportunistic infection, or progression to CD4 count thresholds (≤200 or ≤350 cells/mm3). Secondary outcomes included HIV plasma viral load and CD4 count.ResultsSeven studies were included. No definitive relationship was observed between HSV-2 seropositivity and time to antiretroviral initiation (n=2 studies), CD4≤350 (n=1), CD4≤200 (n=1), death (n=1), viral load (n=6) or CD4 count (n=3). Although two studies each observed trends towards accelerated progression to clinical AIDS/opportunistic infection in HSV-2 seropositives, with pooled unadjusted hazard ratio=1.85 (95% CI=1.12,3.06; I2=2%), most OIs observed in the study for which data were available can occur at high CD4 counts and may not represent HIV progression. In contrast, a single study HSV-2 disease activity found that the presence of genital HSV-2 DNA was associated with a 0.4 log copies/mL increase in HIV viral load.ConclusionsDespite an observation that HSV-2 activity is associated with increased HIV viral load, definitive evidence linking HSV-2 seropositivity to accelerated HIV disease progression is lacking. The attenuating effects of acyclovir on HIV disease progression observed in recent trials may result both from direct anti-HIV activity as well as from indirect benefits of HSV-2 suppression.

The Scarlet H

The Scarlet H

Genital Herpes Simplex Virus Type 2 Infection in Humanized HIV-Transgenic Mice Triggers HIV Shedding and Is Associated With Greater Neurological Disease

Epidemiological studies consistently demonstrate synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1). Higher HIV-1 loads are observed in coinfected individuals, and conversely, HIV-1 is associated with more-severe herpetic disease. A small animal model of coinfection would facilitate identification of the biological mechanisms underlying this synergy and provide the opportunity to evaluate interventions. Mice transgenic for HIV-1 provirus and human cyclin T1 under the control of a CD4 promoter (JR-CSF/hu-cycT1) were intravaginally infected with HSV-2 and evaluated for disease progression, HIV shedding, and mucosal immune responses. HSV-2 infection resulted in higher vaginal HIV loads and genital tissue expression of HIV RNA, compared with HSV-uninfected JR-CSF/hu-cycT1 mice. There was an increase in genital tract inflammatory cells, cytokines, chemokines, and interferons in response to HSV-2, although the kinetics of the response were delayed in HIV-transgenic, compared with control mice. Moreover, the JR-CSF/hu-cycT1 mice exhibited earlier and more-severe neurological disease. The latter was associated with downregulation of secretory leukocyte protease inhibitor expression in neuronal tissue, a molecule with antiinflammatory, antiviral, and neuroprotective properties. JR-CSF/hu-cycT1 mice provide a valuable model to study HIV/HSV-2 coinfection and identify potential mechanisms by which HSV-2 facilitates HIV-1 transmission and HIV modulates HSV-2-mediated disease.

P2.152 Giving Patients What They Want: Disclosure Advice For Sexually Transmitted Infections and Information on Legal Redress Following Infection

BackgroundA recent UK prison sentence for transmission of genital herpes simplex virus (HSV) type 2 has caused STI clinics to reassess patient advice on disclosure. Crown Prosecution Service (CPS) guidance,...

Penile Herpes Simplex Virus Type 1 Infection Presenting Two and a Half Years After Jewish Ritual Circumcision of an Infant

The association between Jewish ritual circumcision and genital herpes simplex virus type 1 infection has been well described. We report a case of genital herpes that first presented at the age of 2½ years. We believe that the infection was acquired asymptomatically through direct orogenital suction performed during circumcision in the newborn period.

Utilization and Cost of Diagnostic Methods for Sexually Transmitted Infection Screening Among Insured American Youth, 2008

Private sector utilization and cost information on testing for sexually transmitted infections (STIs) in the United States is limited. We used current procedural terminology codes for tests for HIV, human papillomavirus (HPV), genital herpes simplex virus type 2, hepatitis B virus, chlamydia, gonorrhea, trichomoniasis, and syphilis. We extracted outpatient claims for persons aged 15 to 24 years in 2008 from the MarketScan database. Utilization was measured as the number of claims per 100,000 enrollees for tests specific to a given infection. We estimated claims rates and average costs by sex, compared these with Centers for Medicare and Medicaid Services (CMS) fees, and estimated the overall total cost of STI testing. The claims rate for HPV was higher than for any other STI (P < 0.001) at 18,085/100,000, whereas that for trichomoniasis was lower than all other STIs (P < 0.001) at 517/100,000. Claims rates for females were higher than for males (P < 0.001) for all STIs. Average costs were as follows: $24 (HIV), $34 (HPV), $29 (hepatitis B virus), $25 (herpes simplex virus type 2), $43 (chlamydia), $42 (gonorrhea), $28 (trichomoniasis), and $24 (syphilis). Costs exceeded CMS fees for 67 of 78 current procedural terminologies by an average of 40%. The estimated total cost for all STIs was $403.1 million for the privately insured population aged 15 to 24 years. We found that the utilization rates and many test costs varied by sex. Private insurers typically paid more than the CMS fee schedule for testing.

The Estimated Direct Medical Cost of Selected Sexually Transmitted Infections in the United States, 2008

Millions of cases of sexually transmitted infections (STIs) occur in the United States each year, resulting in substantial medical costs to the nation. Previous estimates of the total direct cost of STIs are quite dated. We present updated direct medical cost estimates of STIs in the United States. We assembled recent (i.e., 2002-2011) cost estimates to determine the lifetime cost per case of 8 major STIs (chlamydia, gonorrhea, hepatitis B virus, human immunodeficiency virus (HIV), human papillomavirus, genital herpes simplex virus type 2, trichomoniasis and syphilis). The total direct cost for each STI was computed as the product of the number of new or newly diagnosed cases in 2008 and the estimated discounted lifetime cost per case. All costs were adjusted to 2010 US dollars. Results indicated that the total lifetime direct medical cost of the 19.7 million cases of STIs that occurred among persons of all ages in 2008 in the United States was $15.6 (range, $11.0-$20.6) billion. Total costs were as follows: chlamydia ($516.7 [$258.3-$775.0] million), gonorrhea ($162.1 [$81.1-$243.2] million), hepatitis B virus ($50.7 [$41.3-$55.6] million), HIV ($12.6 [$9.5-$15.7] billion), human papillomavirus ($1.7 [$0.8-$2.9] billion), herpes simplex virus type 2 ($540.7 [$270.3-$811.0] million), syphilis ($39.3 [$19.6-$58.9] million), and trichomoniasis ($24.0 [$12.0-$36.0] million). Costs associated with HIV infection accounted for more than 81% of the total cost. Among the nonviral STIs, chlamydia was the most costly infection. Sexually transmitted infections continue to impose a substantial cost burden on the payers of medical care in the United States. The burden of STIs would be even greater in the absence of STI prevention and control efforts.

Editorial Commentary: Changing Epidemiology of Herpes Simplex Virus Infections

The rapid spread of genital herpes simplex virus (HSV) type 2 in the population was recognized in the late 1970s and early 1980s. Indeed, Time magazine featured an article on the subject and recognized HSV as a social plague because of its propensity to cause recurrent genital ulcerative disease and be transmitted either knowingly or unknowingly by sexual contact [1]. The ability of the virus to establish latency in sensory ganglia and reactivate with the proper provocative stimulus is integral to the pathogenesis of infection. Since then HSV-2 infections have attracted global interest because of the medical and psychological morbidity associated with frequent recurrences and the recognition that once someone is infected, there is no cure [2]. Importantly, life-threatening disease caused by HSV-2 in newborns was recognized because of contact with infected maternal genital secretions [3]. Furthermore, the association between genital ulcerative disease caused by HSV2 and increased probability of acquisition of human immunodeficiency virus (HIV) infection, particularly in the developing world, sparked numerous efforts to develop interventions that prevented recurrences and thereby decreased the probability of HIV acquisition [4]. Although antiviral therapies improved the quality of life, none prevented personto-person transmission or the establishment of latency. The National Institutes of Health and private foundations provided significant funding to elucidate the molecular pathogenesis of the disease, develop new therapeutic and diagnostic strategies, and, more recently, develop a vaccine to prevent HSV-2 infections. As these latter vaccine studies were designed and implemented, the primary goal was to reduce the probability of acquisition of HSV-2. Herein lies the fundamental problem: the disease has changed. Bernstein and colleagues have redefined the epidemiology of primary genital

Influence of Methamphetamine on Genital Herpes Simplex Virus Type 2 Infection in a Mouse Model

Use of the stimulant methamphetamine (METH) is increasingly common, with >35 million users worldwide. There is a known association between stimulant use and an increased incidence of HIV and other sexually transmitted infections (STIs). METH is known to have immune modulatory properties. However, the impact of METH on normal immune responses and disease pathogenesis with STIs has not been fully examined. We used a well-characterized murine model to investigate the impact of METH use on genital herpes simplex virus type 2 infection. Plaque assay and quantitative real-time polymerase chain reaction were used to measure viral replication. Cytokine bead array and enzyme-linked immunosorbent assay were used to determine levels of cytokines during host innate immune response. METH treatment altered behavior, onset of clinical signs, and disease progression. METH-treated mice also had a thinned vaginal epithelium and an increase in virus present in the sensory ganglia. In addition, METH produced a local dysregulation of cytokine secretion that contrasts with its minimal impact on systemic cytokine secretion. Results suggest that the METH alterations of the host immune response partially contribute to enhanced genital herpes disease progression. These findings will improve understanding of METH use on host immune responses and susceptibility to disease.

Inactivated HSV-2 in MPL/alum adjuvant provides nearly complete protection against genital infection and shedding following long term challenge and rechallenge

Herpes Simplex Virus Type 2 (HSV-2) infection can result in life-long recurrent genital disease, asymptomatic virus shedding, and transmission. No vaccine to date has shown significant protection clinically. Here, we used a mouse model of genital HSV-2 infection to test the efficacy of a vaccine consisting of whole, formalin-inactivated HSV-2 (FI-HSV2) formulated with monophosphoryl lipid A (MPL) and alum adjuvants. Vaccine components were administered alone or as a prime-boost immunization together with DNA vaccines encoding a truncated glycoprotein D2 (gD2t) and two conserved HSV-2 genes necessary for virus replication, UL5 (DNA helicase) and UL30 (DNA polymerase). Our results show: (1) compared with mock immunized controls, mice immunized with FI-HSV2 plus MPL/alum consistently showed protection against disease burden and total viral shedding while the mice immunized with gD2t protein with MPL/alum did not; (2) protection against genital disease and viral replication correlated with the type of boost in a prime-boost immunization with little advantage afforded by a DNA prime; (3) intramuscular (i.m.) immunization with FI-HSV2 in MPL/Alhydrogel adjuvant provided nearly complete protection against vaginal HSV-2 shedding after a lethal intravaginal (i.vag.) short-term challenge and long-term rechallenge; (4) single formulation immunization with DNA vaccines, FI-HSV2, and MPL in an aluminum phosphate (Adju-Phos) adjuvant did not increase protection relative to FI-HSV2/MPL/Adju-Phos alone; and (5) addition of MPL/alum to the FI-HSV2 was required for optimal protection against disease, viral replication, and latent virus load in the dorsal root ganglia (DRG). Most notably, an optimized vaccine formulation of FI-HSV2 MPL/Alhydrogel given i.m. completely protected against detectable vaginal HSV-2 shedding in the majority of animals and HSV-2 latent DNA in the DRG of all animals.