A Clinical Trial in Healthy Volunteers and Volunteers With Recurrent Genital Herpes to Study the Safety, Tolerability, and Immune Responses After Vaccination With an Investigational Vaccine Designed to Prevent Genital Herpes Lesions

Exclusion Criteria

• •Breastfeeding or intending to become pregnant within the projected duration of the trial starting with Visit 0 until 60 days after receiving the last trial treatment or intending to father children within the projected duration of the trial starting with Visit 0 until 90 days after receiving the last trial treatment.
• •Part A \& B only: Current or history of symptomatic genital herpes infections. Volunteers with oral herpes or herpetic whitlow will not be excluded.
• •Current or history of any form of ocular HSV infection or HSV-related central nervous system disease or complication.
• •History of any serious adverse reactions to vaccines or to vaccine components such as lipids, and including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.
• •Current or history of the following medical conditions:
• •* Uncontrolled or moderate or severe respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease); symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program Expert Panel report;
• •* History of thyroidectomy, or thyroid disease requiring medication during the last 12 months;
• •* History of diabetes mellitus type 1 or type 2, including cases controlled with diet alone (not excluded: history of isolated gestational diabetes);
• •* Hypertension (elevated blood pressure or hypertension during screening or previously that is not well controlled only \[consistently ≤140 mm Hg systolic and ≤90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤150 mm Hg systolic and ≤90 mm Hg diastolic at enrollment\] or if systolic blood pressure ≥150 mm Hg at enrollment or diastolic blood pressure ≥100 mm Hg confirmed by two measurements prior to enrollment);
• •* Malignancy within 5 years of Visit 0, excluding localized basal or squamous cell cancer;
• •* Current or history of cardiovascular diseases, e.g., myocardial infarction, congestive heart failure, cardiomyopathy, or clinically significant arrhythmias, myocarditis, or pericarditis;
• •* Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions);
• •* Seizure disorder: History of seizure(s) within past 3 years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
• •History of psychiatric illness, including alcohol abuse or drug addiction within 1 year before Visit 0, or a history (within the past 5 years) of substance abuse or known medical, psychological, or social conditions which, in the opinion of the investigator, could compromise their wellbeing if they participate as participants in the trial, or that could prevent, limit, or confound the protocol specified assessments.
• •Any of the following associated with immune dysregulation:
• •* Primary immunodeficiencies.
• •* History of solid organ or bone marrow transplantation.
• •* Asplenia: any condition resulting in the absence of a functional spleen.
• •* Currently existing or history of autoimmune disease including and not limited to thyroid autoimmune disease, multiple sclerosis, psoriasis, etc.
• •Use of any non-trial IMP within 28 days before Dose 1 (Visit 1) (Parts A \& B) or before Pre-dose Visit 2 (Part C) in this trial or planned receipt continuously until Visit 6 (Part C) or Visit 12 (Parts A \& B) in this trial, or participation in the active treatment phase of another interventional clinical trial.
• •Previous vaccination with an investigational herpes virus vaccine at any time.
• •Any non-trial vaccination with a licensed live attenuated vaccine within 28 days before and after each dose, or within 14 days before and after each dose for all other licensed vaccines.
• •Received allergy treatment with antigen injections within 28 days before first IMP administration or that are scheduled within 14 days after Visit 1.
• •Received blood/plasma products or immunoglobulin within 120 days before Visit 1 or planned administration starting at Visit 0 until completion of Visit 6 (Part C) or Visit 12 (Parts A \& B).
• •Part A \& B only: Received chronic suppressive antiviral therapy for treatment of recurrent HSV-1 and/or HSV-2 genital herpes infections (i.e., oral acyclovir, oral valacyclovir, oral famciclovir, and/or intravenous ganciclovir) from 1 year prior to Visit 0 until completion of Visit 12.
• •Any existing condition which may affect vaccine injection and/or assessment of local reactions assessment at the injection site, e.g., tattoos, severe scars.
• •Vulnerable individuals as per International Council for Harmonisation (of Technical Requirements for Pharmaceuticals for Human Use) (ICH) E6 definition, i.e., are individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. This includes investigator site staff directly involved in the conduct of the trial and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the trial and their family members.
• •Part A \& B only: Any screening hematology and/or blood chemistry laboratory value that meets the definition of a Grade ≥2 abnormality at Visit 0. For laboratory values for which toxicity grading guidance is not available or for Grade ≤1 abnormalities, participant eligibility will be determined at the discretion of the investigator.
• •Part C only: Any screening hematology and/or blood chemistry laboratory value that meets the definition of a Grade ≥3 abnormality at Visit 0. Grade 2 abnormal laboratory values may be retested; if the result is confirmed, the participant must be excluded. For laboratory values for which toxicity grading guidance is not available, or for Grade ≤1 abnormalities, participant eligibility will be determined at the discretion of the investigator.
• •Part B only: Applicable HSV serology stratum is already full or the HSV serostatus is reported as indeterminate.
• •Part C only: At the end of the first 28-day swabbing period, a participant has submitted fewer than 45 swabs.
• •Part C only: If a participant has evidence of active genital herpes infection (prodrome or lesions) at the Dose 1 visit which had already been delayed due to presence of lesions at previously scheduled Dose 1.