A Lassa Fever Vaccine Trial in Adults and Children Residing in West Africa

Inclusion Criteria:

• Adults, adolescents, and children in good general health as assessed by medicalhistory and physical examination (group-specific criteria apply).

• At least 18 months old on the day of screening and not more than 70 years old on theday of vaccination (group-specific criteria apply).

• Participant or parent/guardian willing to comply with the requirements of theprotocol and available for follow-up for the planned duration of the study.

• In the opinion of the Principal Investigator (PI) or designee and based onAssessment of Informed Consent Understanding (AOU), participant or parent/guardianhas understood the information provided and potential impact and/or risks linked toadministration and participation in the trial; written informed consent will beobtained before any study-related procedures are performed. Children old enough tounderstand the procedures will be asked to assent, in addition to parent/guardianconsent, in accordance with local requirements.

• Willing to undergo HIV testing, risk reduction counselling, and receive HIV testresults (group-specific timepoints apply).

• All participants of child-bearing potential engaging in sexual activity that couldlead to pregnancy must commit to use an effective hormonal contraception orintrauterine device beginning 2 weeks prior and extending for 4 months followingreceipt of vaccine/placebo. Study sites will choose which methods are mostappropriate for their population and this will be specified in the Informed ConsentDocument (ICD).

• All sexually active participants must consistently use male or female condoms withall sexual partners for 4 months following IP administration.

• All participants who are not engaging in sexual activity that could lead topregnancy at screening must agree to utilize an effective method of contraception ifthey begin engaging in sexual activity that could lead to pregnancy, as outlinedabove.

• All participants of childbearing potential must be willing to undergo a pregnancytest at time points indicated in the SOA.

• Willing to forgo donation of blood or any other tissues for transfusion ortransplantation, from screening onward throughout the course of the study.

Additional Inclusion Criteria For HIV-Infected Participants

• Adults who are HIV-infected must meet the following additional inclusion criteria:

• Participant must be aged at least 18 years old on the day of screening and not morethan 50 years old on the day of vaccination.

• Participant must have documented HIV-1 or HIV-2 infection for at least 6 monthsprior to screening.

• Participant must be on a stable (at least 6 months) regimen of Highly ActiveAntiretroviral Therapy (HAART), as defined as potent anti-HIV treatment including acombination of antiretroviral agents (pre- or post-exposure prophylaxis does notcount as HAART).

• Participant entering the study should have a screening viral load <50 copies/ml.

• Participant must be willing to continue their HAART and HIV care follow upthroughout the study as directed by their regular caregiver and be willing to giveaccess to records of their ongoing care.

• Participant must be in an otherwise reasonably good medical condition (absence ofacquired immunodeficiency syndrome [AIDS]-defining illnesses or clinicallysignificant disease), diagnosed based on physical examination, medical history, andthe investigator's clinical judgment.

Additional Inclusion Criteria for Pediatric Participants

• Each potential pediatric study participant must meet all of the following additionalcriteria to be enrolled in the study:

• Parent(s)/legal guardian must have signed an ICD indicating that they understand thepurpose and procedures required for the study, are willing/able to adhere to thestudy requirements and are willing for their child to participate in the study.Assent must be obtained from adolescents and children in accordance with localregulations and practice. Parent(s)/legal guardian must pass the AOU.

• Participant's age on the day of vaccination is within one of the 3 age strata in thestudy: 12-17 years, 6-11 years, or 18 months -5 years.

• Participant must be healthy in the investigator's clinical judgment (and theparent(s)/legal guardian's judgment) based on medical history, physical examinationand vital signs performed at screening.

• A female adolescent who is of childbearing potential must comply with requirementsfor contraception.

• Adolescents who are sexually active must comply with requirement for use of condomsfor 4 months after vaccination.

• Participant has received all routine immunizations appropriate for their age asreported by the parent(s)/legal guardian, according to local routine vaccinationschedules. Participants are allowed to catch up on routine immunizations if neededor as part of national immunization campaigns. However, Exclusion Criteria #9 willapply.

Exclusion Criteria:

• Confirmed HIV-1 or HIV-2 infection (except as outlined for Group 2)

• Any clinically relevant abnormality on history or examination including history ofimmunodeficiency (except for Group 2) or autoimmune disease; use of corticosteroids,immunosuppressive, anticancer, or other medications considered significant by theInvestigator within the previous 6 months. The following exceptions are permittedand will not preclude study participation: use of corticosteroid nasal spray forrhinitis, topical corticosteroids for an acute uncomplicated dermatitis; or a shortcourse (duration of 10 days or less, or a single injection) of corticosteroid for anon-chronic condition (based on Investigator clinical judgment) at least 2 weeksprior to enrollment in this study.

• Any clinically significant chronic medical condition that, in the opinion of theInvestigator, makes the participant unsuitable for participation in the study (except for HIV in Group 2). Note: Participants aged >50years with the followingchronic but controlled conditions may be enrolled:

• Hypertension with systolic ≤150 mmHg and/or diastolic ≤90 mmHg; (regardless oftreatment status)

• Diabetes mellitus with a HbA1C <10% and /or with type 2 diabetes mellitus on stablemedication for at least 2 months prior to enrollment.

• Pregnant or lactating.

• Bleeding disorder that was diagnosed by a physician (eg, factor deficiency,coagulopathy, or platelet disorder that requires special precautions). Note: Aparticipant who states that he or she has easy bruising or bleeding but does nothave a formal diagnosis and has intramuscular (IM) injections and blood drawswithout any adverse experience is eligible.

• Infectious disease: chronic active hepatitis B infection (HBsAg-positive), currenthepatitis C infection, prior clinical diagnosis of Lassa Fever disease (LF) or Ebolavirus disease (EVD) by medical history, active syphilis (positive screening andconfirmatory tests unless adequately treated), positive viral detection test forSARS-CoV-2. Note: COVID-19 screening is not applicable for Group 5.

• History of splenectomy or functional asplenia.

• Any of the following abnormal laboratory parameters listed below:

• Hematology

• Absolute Neutrophil Count (ANC): ≤1,000 cells/mm3 or ≤ 1.0 × 109 cells/L

• Absolute Lymphocyte Count (ALC): ≤650 cells/mm3 or ≤ 0.65 × 109 cells/L

• Hemoglobin: <9.5 g/dl in females; <11.0 g/dl in males; <10 g/dl in children <11years of age

• Platelets <100,000 cells/mm3

• Chemistry

• Creatinine >1.1 x upper limit of normal (ULN) (Note: For participants aged >50 yearsclinically insignificant renal insufficiency defined as creatinine ≤1.3 x ULN isallowed)

• Alanine transaminase (ALT) >1.25 x ULN

• Aspartate transaminase (AST) >1.25 x ULN

• Urinalysis (not applicable for group 5)

• Clinically significant abnormal dipstick confirmed by repeat dipstick on newspecimen or by microscopy

• Protein = 1+ or more

• Blood = 2+ or more (not due to menses) (Urinalysis may be collected within thefollowing 2 weeks if menses interfere)

• Receipt of any vaccine within the previous 28 days or planned receipt within 28 daysafter vaccination with IP. Participation may be delayed until this criterion can befulfilled. Note: prior receipt of VSV-vectored vaccines such as VSV-ZEBOV will bedocumented but is not an exclusion criterion.

• Prior receipt of another investigational Lassa vaccine candidate. Note: receipt ofplacebo in a previous LF vaccine trial will not exclude a participant fromparticipation if documentation is available and the Medical Monitor gives approval.

• Receipt of blood transfusion or blood-derived products within the previous 3 months.

• Participation in another clinical trial or observational study currently, within theprevious 3 months, or expected participation during this study, unless MedicalMonitor approves.

• History of severe local or systemic reactogenicity to any vaccine (eg, anaphylaxis,respiratory difficulties, angioedema, injection site necrosis, or ulceration).

• Psychiatric condition or substance abuse that compromises safety of the participantand precludes compliance with the protocol. Specifically excluded are persons withpsychoses in the last 3 years prior to screening, ongoing risk for suicide, orhistory of suicide attempt or gesture in the last 3 years prior to screening.

• Seizure disorder: A participant who has had a seizure in the last 3 years prior toscreening or has been on any medication to control or prevent seizures for the last 3 years is excluded. Group 5: History of febrile seizures is an exclusion criterion.

• A history of malignancy in the past 5 years (prior to screening) or ongoingmalignancy (a history of a completely excised malignancy that is considered cured isnot an exclusion).

• Active, serious infections requiring parenteral antibiotic, antiviral, antiparasiticor antifungal therapy within 30 days prior to enrollment (except HAART treatment inGroup 2). Asymptomatic malaria infection at study entry will be assessedretrospectively and will not be a basis for exclusion.

• Group specific weight for height restrictions as indicated below:

• Groups 1 and 2: Obesity as defined by Body mass index (BMI) ≥35.

• Group 3: Obesity as defined by weight for height 2 standard deviation (SD) frommedian according to WHO growth charts or underweight as defined by weight for heightor weight for length ≤-2 SD from median according to WHO growth charts

• Groups 4 and 5: Underweight as defined by weight for height or weight for length ≤ 2SD from median according to WHO growth charts (see APPENDIX C) and/or weighing <10kg.

• Group specific hearing thresholds or otoacoustic emission (OAE) results at 0.5-4KHzas indicated below:

• Moderate or greater hearing impairment defined as 35dB in any frequency in eitherear as revealed via the audiometry exam for Groups 1 and 2.

• Mild or greater hearing impairment defined as ≥20dB in any frequency in either earas revealed via the audiometry exam for adolescents and children aged >7years.

For children 7 years of age and younger (or unable to follow pure tone audiometry procedure) "refer" test results as determined by OAE.

• Otorrhea within the past 90 days, sudden or rapid hearing loss within the past 90days, acute or chronic dizziness, otalgia (external ear otalgia is not an exclusion)

• Clinically relevant abnormal otoscopy, that in the opinion of the investigator, mayinterfere with hearing. (Participants with conditions that can be treated prior toenrolment such as cerumen obstruction are not excluded)

• History of acute or chronic or severe neurologic condition (eg, diagnosis ofGuillain-Barré syndrome, epilepsy, Bell's palsy, meningitis, or disease with anyfocal neurologic deficits).

• Current of past significant risk factors for hearing loss (eg, occupational exposureto loud noise or medical illness) that, in the opinion of the investigator, mayinterfere with the detection of changes in hearing during the study.

• History of any condition associated with sensorineural hearing loss that, in theopinion of the investigator, may cause changes in hearing during the study (eg,occupational exposure to loud noise or medical illness).

• If, in the opinion of the PI, it is not in the best interest of the participant toparticipate in the study.