HSV, Herpes Labialis
Conditions
Keywords
Squaric Acid, Squaric acid dibutyl ester, cold sores
Brief summary
Subjects were recruited who were positive for antibody against herpes simplex virus type 1 (HSV-1) and self-reported having in the previous 12 months * 6 or more herpes labialis outbreaks (group A), * 1 or 2 outbreaks (group B), or * zero outbreaks (group C). Twelve subjects in each group were recruited. Blood was collected from these persons and peripheral blood mononuclear cells (PBMCs) isolated and tested for proliferation in vitro when stimulated with HSV-1-infected cell extracts, free HSV-1 virus, or Candida albicans extract. Candida albicans is a ubiquitous infectious fungus and its extract is used as a test of general immune response. RNA was also isolated from the PBMCs after incubation in the three stimuli and expression of 41 immune-related genes quantified by quantitative real-time PCR. Also serum anti-HSV-1 IgG levels were quantified. After the blood collection on day 1, the persons in group A (frequent cold sore sufferers) were treated with a single topical application of 2% squaric acid dibutyl ester (SADBE) in DMSO, applied to the inner aspect of the upper arm. These subjects returned on days 15 and 57 for blood collection, and their PBMCs were tested again on those dates for proliferation in vitro against the same stimuli and for gene expression and for serum anti-HSV-1 IgG levels.
Detailed description
Primary oral infection with the herpes simplex virus (HSV) typically occurs at a young age, is asymptomatic, and is not associated with significant morbidity. After primary oral infection, HSV may persist in a latent state in the trigeminal ganglion and later reactivate as the more common herpes labialis, or cold sores. Common triggers for reactivation are well known and include ultraviolet light, trauma, fatigue, stress, fever, inflammation, and menstruation. These lesions affect up to 45 percent of the U.S. population. They classically manifest as a well-localized cluster of small vesicles along the vermilion border of the lip or adjacent skin. The vesicles subsequently rupture, ulcerate, and crust within 24 to 48 hours. Spontaneous healing occurs over seven to 10 days. In immunocompetent patients, herpes labialis usually is mild and self-limited. However, pain, swelling, and cosmetic concerns may prompt physician consultation. Orally administered antiviral agents, such as acyclovir (Zovirax) or valacyclovir (Valtrex), have a modest clinical benefit if initiated during the prodrome. Topical treatment with 1% penciclovir cream (Denavir) may reduce healing time and pain slightly, even if initiated after the prodrome. However, reduction in healing time with systemic or topical agents is modest. Squaric acid dibutyl ester (SADBE) is a topical immunotherapeutic agent used in the treatment of verruca vulgaris and alopecia areata. During a recent FDA Compounding Advisory Committee Meeting, it was recommended that squaric acid dibutylester be included on the list of bulk drug substances allowed for use in compounding under section 503A of the Federal Food, Drug, and Cosmetic Act. And SADBE has now been so listed under section 503A. A study completed by Lee et al of 29 patients with recalcitrant warts demonstrated complete clearance in 69% of patients with application every 2-4 weeks. Silverberg et al showed a complete clearance in 58% of patients (n=61) when SADBE was applied 3 times weekly. SADBE has also been used with some success in the treatment of alopecia areata. In a review of the literature, Rokhsar et al noted a 50% to 60% success rate of SADBE in use for hair re-growth in this population. SADBE has been reported to cause eczema, lymphadenopathy, blistering, allergic contact dermatitis, skin hypopigmentation, a burning sensation after application, and systemic reactions including fever and arthralgias. A study completed by Oglio et al of eight patients treated with SADBE for warts noted only mild and well tolerated side effects of erythema, desquamation, cutaneous edema, pruritus, burning, and pain. SADBE induces a delayed-type hypersensitivity response which in warts, is believed to induce the killing of virally infected cells by cytotoxic lymphocytes. This influx of lymphocytes into lesional Page 4 of 14 tissue may also enhance the recognition and processing of viral antigens, leading to clonal expansion of effector cells. It is hoped that SADBE will offer subjects a safe and effective therapeutic option to decrease the frequency and severity of future herpes labialis outbreaks through these mechanisms. A placebo-controlled clinical study completed at Massachusetts General Hospital showed that squaric acid prevented recurrence of herpetic lesions. The effect of SADBE of delaying new herpes labialis outbreaks was highly significant (p\<0.01) as compared to placebo.
Interventions
2% squaric acid dibutyl ester (SADBE) (Supplied by Squarex) is topically applied to the inner aspect of the upper arm of the subject and covered with Tegaderm. Subject is advised to wash it off after 3 hours.
Sponsors
Squarex, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
NONE
Intervention model description
Subjects will be recruited in three groups, all of whom are infected with HSV-1, as shown by having IgG against HSV-1: x Group A: 12 subjects with 6 or more herpes labialis outbreaks in the past 12 months x Group B: 12 subjects with 1 to 2 outbreaks in the past 12 months x Group C: 12 subjects with zero outbreaks in the past 12 months Subjects in group A will receive 2% SADBE dose on the arm after their initial blood samples are obtained. Group A subjects will have blood collected and tests repeated 2 and 8 weeks later. Subjects in Groups B and C will be matched to the subjects in Group A so that demographic characteristics (i.e., gender distribution, age and weight) are within broadly similar ranges.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 and \<65 2. Positive test for IgG against herpes simplex virus type 1 (HSV-1). 3. Groups A and B only: Clinical diagnosis of herpes labialis, which may be made at the screening visit based on the patient's self-reported history of symptoms. An active herpes labialis outbreak at the time of entry into the clinical trial will neither be required nor will be an
Exclusion criteria
. 4. Group A only: Self report having six or more episodes of herpes labialis in the past 12 months. Subjects will NOT be told that six-or-more episodes in the previous 12 months is the entry criterion. Subjects will be asked How many separate episodes of cold sores have you had in the previous 12 months? They will be included if they give an answer of six or more and excluded from Group A if they give an answer of five or fewer. 5. Group A only: At least half of the subject's episodes of the previous 12 months should be vesicular in nature and at least half preceded by prodromal symptoms. 6. Group B only: Self report having exactly 1 or 2 episodes of herpes labialis in the past 12 months. Subjects will NOT be told that one or two episodes in the previous 12 months is the entry criterion. Subjects will be asked How many separate episodes of cold sores have you had in the previous 12 months? They will be included if they give an answer of one or two and excluded from Group B if they give a different answer. 7. Group C only: Self report having zero episodes of herpes labialis in the past 12 months. Subjects will NOT be told that zero episodes in the previous 12 months is the entry criterion. Subjects will be asked How many separate episodes of cold sores have you had in the previous 12 months? They will be included if they give an answer of zero and excluded from Group C if they give an answer of one or more.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | Baseline and 8 weeks after baseline (Day 1) +/- 7 days for subjects with less than 6 herpres labialis outbreaks in 12 months, relative to baseline for subjects with 6 or greater herpes labialis outbreaks | RNA gene expression of interleukin-5 (IL5) and interferon gamma (IFNG) genes in PBMCs exposed in vitro to 4 conditions: no stimulus, HSV-1 virus, HSV-1-infected cell extracts, and Candida albicans extract. Measure is qRT-PCR crossing threshold (Ct), where a lower number is higher gene expression. A lower Ct of 1 is approximately a 2-fold higher expression level of the gene. |
| Immune Monitoring - PBMC Proliferation | Baseline | PBMC proliferation in response to 3 stimuli: HSV-1 virus, HSV-1-infected cell extracts, and Candida albicans extract. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 6 or More Herpes Labialis Outbreaks Subjects will be recruited in three groups, all of whom are infected with HSV-1, as shown by having IgG against HSV-1:
Group A: 12 subjects with 6 or more herpes labialis outbreaks in the past 12 months.
Subjects in group A will receive 2% Squaric Acid Dibutyl Ester (SADBE) dose on the arm after their initial blood samples are obtained. Group A subjects will have blood collected and tests repeated 2 and 8 weeks later.
Subjects in Groups B and C will be matched to the subjects in Group A so that demographic characteristics (i.e., gender distribution, age and weight) are within broadly similar ranges.
Squaric Acid Dibutyl Ester: 2% squaric acid dibutyl ester (SADBE) (Supplied by Squarex) is topically applied to the inner aspect of the upper arm of the subject and covered with Tegaderm. Subject is advised to wash it off after 3 hours. | 12 |
| 1 or 2 Herpes Labialis Outbreaks Subjects will be recruited in three groups, all of whom are infected with HSV-1, as shown by having IgG against HSV-1:
Group B: 12 subjects with 1 to 2 outbreaks in the past 12 months. Subjects in Groups B and C will be matched to the subjects in Group A so that demographic characteristics (i.e., gender distribution, age and weight) are within broadly similar ranges. Invite these back for a further blood draw on Day 0. | 12 |
| Zero Herpes Labialis Outbreaks Subjects will be recruited in three groups, all of whom are infected with HSV-1, as shown by having IgG against HSV-1:
Group C: 12 subjects with zero outbreaks in the past 12 months. Subjects in Groups B and C will be matched to the subjects in Group A so that demographic characteristics (i.e., gender distribution, age and weight) are within broadly similar ranges. Invite these back for a further blood draw on Day 0. | 12 |
| Total | 36 |
Baseline characteristics
| Characteristic | 1 or 2 Herpes Labialis Outbreaks | 6 or More Herpes Labialis Outbreaks | Zero Herpes Labialis Outbreaks | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 12 Participants | 36 Participants |
| Age, Continuous | 51.71 years | 51.71 years | 54.30 years | 52.57 years |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 11 Participants | 9 Participants | 29 Participants |
| Region of Enrollment United States | 12 participants | 12 participants | 12 participants | 36 participants |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 8 Participants | 26 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 3 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Immune Monitoring - PBMC Proliferation
PBMC proliferation in response to 3 stimuli: HSV-1 virus, HSV-1-infected cell extracts, and Candida albicans extract.
Time frame: Baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Immune Monitoring - PBMC Proliferation | HSV-1-infected cell extracts | 16.73 percent proliferation | Standard Error 3.94 |
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Immune Monitoring - PBMC Proliferation | HSV-1 virus | 8.26 percent proliferation | Standard Error 1.98 |
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Immune Monitoring - PBMC Proliferation | Candida extract | 4.47 percent proliferation | Standard Error 1.53 |
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Immune Monitoring - PBMC Proliferation | Normalized all three stimuli | 68.33 percent proliferation | Standard Error 10.42 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Immune Monitoring - PBMC Proliferation | Normalized all three stimuli | 83.21 percent proliferation | Standard Error 13.53 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Immune Monitoring - PBMC Proliferation | HSV-1-infected cell extracts | 19.26 percent proliferation | Standard Error 5.57 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Immune Monitoring - PBMC Proliferation | Candida extract | 4.85 percent proliferation | Standard Error 1.51 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Immune Monitoring - PBMC Proliferation | HSV-1 virus | 11.71 percent proliferation | Standard Error 2.98 |
| Group C: Zero Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Immune Monitoring - PBMC Proliferation | Normalized all three stimuli | 99.98 percent proliferation | Standard Error 13.92 |
| Group C: Zero Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Immune Monitoring - PBMC Proliferation | HSV-1 virus | 12.70 percent proliferation | Standard Error 3.05 |
| Group C: Zero Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Immune Monitoring - PBMC Proliferation | Candida extract | 7.83 percent proliferation | Standard Error 2.19 |
| Group C: Zero Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Immune Monitoring - PBMC Proliferation | HSV-1-infected cell extracts | 20.19 percent proliferation | Standard Error 4.47 |
Primary
Immune Monitoring - PBMC Proliferation
PBMC proliferation in response to 3 stimuli: HSV-1 virus, HSV-1-infected cell extracts, and Candida albicans extract.
Time frame: Day 1 and 8 weeks from Day 1 (Initial visit) +/- 7 days for subjects with 6 or more herpes labalis outbreaks
Population: Only subjects with 6 or more herpes labialis outbreaks were treated, therefore only subjects with 6 or more outbreaks are included in this analysis. This set of data compares them at Day 1, before treatment, and analyzed at 8 weeks from Day 1 treatment. Data were not collected at 8 weeks on the subjects with 1 or 2 outbreaks or with zero outbreaks. Data at day 1 on those groups and the subjects with 6 or more outbreaks is reported in Outcome Measure 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Immune Monitoring - PBMC Proliferation | HSV-1-infected cell extracts | 16.96 percent proliferation | Standard Error 2.62 |
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Immune Monitoring - PBMC Proliferation | HSV-1 virus | 13.37 percent proliferation | Standard Error 2.38 |
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Immune Monitoring - PBMC Proliferation | Candida extract | 7.35 percent proliferation | Standard Error 2.42 |
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Immune Monitoring - PBMC Proliferation | Normalized all three stimuli | 99.97 percent proliferation | Standard Error 13.11 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Immune Monitoring - PBMC Proliferation | Normalized all three stimuli | 73.75 percent proliferation | Standard Error 11.56 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Immune Monitoring - PBMC Proliferation | HSV-1-infected cell extracts | 16.73 percent proliferation | Standard Error 3.94 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Immune Monitoring - PBMC Proliferation | Candida extract | 4.47 percent proliferation | Standard Error 1.53 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Immune Monitoring - PBMC Proliferation | HSV-1 virus | 8.26 percent proliferation | Standard Error 1.98 |
Primary
Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline
RNA gene expression of interleukin-5 (IL5) and interferon gamma (IFNG) genes in PBMCs exposed in vitro to 4 conditions: no stimulus, HSV-1 virus, HSV-1-infected cell extracts, and Candida albicans extract. Measure is qRT-PCR crossing threshold (Ct), where a lower number is higher gene expression. A lower Ct of 1 is approximately a 2-fold higher expression level of the gene.
Time frame: Baseline and 8 weeks after baseline (Day 1) +/- 7 days for subjects with less than 6 herpres labialis outbreaks in 12 months, relative to baseline for subjects with 6 or greater herpes labialis outbreaks
Population: Absolute gene expression for Group A on Day 57, Group B on day 1 and Group C on day 1 compared to Group A on Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 in negative control | 10.073 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 0.544 |
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 with HSV-1-infected cell extract stimulus | 9.624 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 0.666 |
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 with HSV-1 virus stimulus | 9.747 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 0.697 |
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 with Candida stimulus | 10.680 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 0.941 |
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in negative control | 10.033 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 0.82 |
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in HSV-1-infected cell extracts stimulus | 6.040 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.681 |
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in HSV-1 stimulus | 7.384 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.67 |
| Group A: 6 or More Herpes Labialis Outbreaks, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in Candida stimulus | 8.421 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 2.053 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in HSV-1-infected cell extracts stimulus | 3.898 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.9 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in negative control | 10.210 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.32 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 with HSV-1-infected cell extract stimulus | 10.983 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 0.971 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in Candida stimulus | 6.167 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 2.98 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in HSV-1 stimulus | 5.554 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 2.65 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 with Candida stimulus | 10.806 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.093 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 with HSV-1 virus stimulus | 10.736 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 0.88 |
| Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 in negative control | 11.380 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.233 |
| Group C: Zero Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in HSV-1 stimulus | 5.789 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.923 |
| Group C: Zero Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 with HSV-1 virus stimulus | 10.414 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.217 |
| Group C: Zero Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 with Candida stimulus | 11.051 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.332 |
| Group C: Zero Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in negative control | 9.729 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.902 |
| Group C: Zero Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in HSV-1-infected cell extracts stimulus | 4.992 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 2.418 |
| Group C: Zero Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in Candida stimulus | 7.336 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.957 |
| Group C: Zero Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 in negative control | 10.711 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.274 |
| Group C: Zero Herpes Labialis Outbreaks in Prior 12 Months, Day 1 | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 with HSV-1-infected cell extract stimulus | 10.986 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.268 |
| Group A, Day 57. Subjects With 6 or More Outbreaks, 8 Weeks After Single Dose of SADBE. | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 with HSV-1 virus stimulus | 10.595 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 0.957 |
| Group A, Day 57. Subjects With 6 or More Outbreaks, 8 Weeks After Single Dose of SADBE. | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 with Candida stimulus | 10.536 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.215 |
| Group A, Day 57. Subjects With 6 or More Outbreaks, 8 Weeks After Single Dose of SADBE. | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 with HSV-1-infected cell extract stimulus | 10.627 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 0.81 |
| Group A, Day 57. Subjects With 6 or More Outbreaks, 8 Weeks After Single Dose of SADBE. | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IL5 in negative control | 11.431 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.143 |
| Group A, Day 57. Subjects With 6 or More Outbreaks, 8 Weeks After Single Dose of SADBE. | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in negative control | 9.718 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.164 |
| Group A, Day 57. Subjects With 6 or More Outbreaks, 8 Weeks After Single Dose of SADBE. | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in Candida stimulus | 5.327 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 2.696 |
| Group A, Day 57. Subjects With 6 or More Outbreaks, 8 Weeks After Single Dose of SADBE. | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in HSV-1 stimulus | 3.923 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.548 |
| Group A, Day 57. Subjects With 6 or More Outbreaks, 8 Weeks After Single Dose of SADBE. | Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline | IFNG in HSV-1-infected cell extracts stimulus | 3.522 q-RT-PCR crossing threshold cycle (Ct) | Standard Deviation 1.6 |