A Randomized, Placebo-controlled Trial, to Evaluate the Safety, Immunogenicity and the Optimal Dose of MOPEVAC-Las Vaccine Candidate Against Lassa Fever

72 subjects will be enrolled in three treatment groups: treatment group A will receive a "low" dose vaccine, treatment group B an "intermediate" dose vaccine and treatment group C a "high" dose vaccine. In addition, 6 subjects will receive a placebo in each treatment group.

Participants will:

• Receive an two injections of MOPEVAC-Las vaccine candidate or placebo, on days 0 and 60
• Visit the clinical site for 11 visits. Among them, one is the screening visit, two correspond to injection visits and 8 are follow-up visits.

Each subject will participate in the trial for 14 months.

Inclusion criteria

• Males and females between the ages of 18 and 55 years (at the time of consent).
• Healthy participant, according to the investigator's clinical judgment, as established by medical history, vital signs, physical examination, and laboratory assessments.
• Participant with a body mass index (BMI) between 18,5 kg/m2 and 30.0 kg/m2.
• Provide written informed consent before initiation of any study procedures.
• A female participant is eligible for this study if she is not pregnant, given by a negative serum pregnancy test at screening and a negative urine pregnancy test at V1 (first injection), nor breastfeeding and if she meets any of the following criteria:

• Of non-childbearing potential (i.e., women who have had a hysterectomy or surgical tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year).
• Of childbearing potential but having sexual relations exclusively with female partners.
• Of childbearing potential but has been and agrees to continue practicing highly effective contraception or abstinence (if this is the preferred and usual lifestyle of the participant) from 30 days prior to vaccination up to 6 months after the last injection (D242).

Highly effective methods of contraception include 1 or more of the following:

• Male partner who is sterile prior to the female participants entry into the study and is the sole sexual partner for the female participant
• Compliant hormonal therapy (oral, intravaginal, transdermal, implantable or injectable)
• An intrauterine hormone-releasing system (IUS)
• An intrauterine device (IUD) with a documented failure rate of < 1%
• A female participant is eligible if she agrees to abstain from donating oocyte from the screening visit up to 6 months after the last injection (D242)
• A male participant is eligible if he agrees to:

• Use a condom (with/without spermicidal product) from the screening visit up to 6 months after the last injection (D242) except if the male participant is sterile; the unique female sexual partner is postmenopausal (defined as no menses for 12 months without an alternative medical cause), is permanently sterilized (e.g. hysterectomy or tubal ligation), or use a highly effective method of contraception; or if he has sexual relations exclusively with male partners
• Not donate sperm from the screening visit up to 6 months after the last injection (D242)
• Not plan to father a child from the screening visit up to 6 months after the last injection (D242)
• Negative HIV 1/2 antibody/antigen test, Hepatitis B surface antigen (HBsAg), and Hepatitis C virus (HCV) antibody.
• Able to understand and comply with planned study procedures and willing to be available for all study-required procedures, visits and calls for the duration of the study.
• Willing to abstain from donating whole blood or blood derivatives, tissue or organ all along the study.
• Affiliated to a social security system (except state medical aid).

Exclusion criteria

• Subjects previously infected by Lassa Virus.
• Previous vaccination with an investigational Lassa fever vaccine.
• Subjects who travelled in the past 12 months prior the first injection or plan to travel during the study in a Lassa-endemic country .
• Subjects who used to live in a Lassa-endemic country, or who are regularly traveling to a Lassa-endemic country.
• History of presence of pulmonary disorders (e.g. COPD, etc.) or asthma in adulthood.
• History of or present thrombocytopenia and/or bleeding disorders.
• History of or present hearing deficiency or tympanic vulnerability (e.g. manifested by recurrent ear infections).
• A positive serum pregnancy test at screening or urine pregnancy test prior to study injection, women who are planning to become pregnant during the study, or women who are breastfeeding.
• Clinically relevant history of or current renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, hematological, endocrine, inflammatory, autoimmune, central nervous system or neurological diseases or clinically relevant abnormal laboratory values.
• Use of immunosuppressive drugs like corticosteroids (excluding topical preparations and inhalers) within 3 months prior to the first vaccination or 6 months for chemotherapies and all along the study.
• A diagnosis of schizophrenia, bipolar disease, or history of hospitalization for a psychiatric condition or previous suicide attempt.
• A history of treatment for any other psychiatric disorder in the past 3 years that increases the risk to the subject in the opinion of the investigator.
• Received immunoglobulin or other blood product within 3 months prior to enrollment or planned receipt of immunoglobulin or a blood product through study completion.
• Vaccination within 3 weeks prior to first injection or planning to receive any licensed vaccine before D88 (e.g. COVID-19 vaccine, Inactivated influenza vaccine).
• History of severe adverse reactions to vaccine administration, including anaphylaxis and related symptoms, such as urticaria, respiratory difficulty, angioedema and abdominal pain to vaccines, or history of known or suspected allergic reaction likely to be exacerbated by any component of the MOPEVAC-Las vaccine.
• Participation in another investigational clinical study within four weeks before the screening visit or planned before the study completion.
• Individuals who are living and/or working with severely immunocompromised people, pregnant women, lactating women, children under 12 months old, or any other individual that, in the judgment of the investigator, might be at increased risk.
• Individual in a direct relationship with an investigator/study team or with the sponsor. Direct dependent relationships include close relatives (e.g. children, parents, partner, siblings, etc.) as well as employees of the clinical study site or the sponsor.
• Any condition that, in the opinion of the investigator, may interfere with the aim of the study or the safety or wellbeing of the subject.
• Subjects with confirmed or suspected immunodeficiency.
• Exposure to an individual with confirmed Lassa virus within the past 3 weeks prior to enrollment.
• Subject with an acute disease and/or fever (body temperature ≥ 38°C) at the time of the 1st vaccination visit.
• Current heavy smoker defined as smoking at least 20 cigarettes (1 pack, or equivalent) per day or former heavy smoker who was an active heavy smoker within the last year prior to the screening visit or has a total smoking history of ≥ 1 pack per day for 10 years or more; or excessive use of electronic cigarettes according to the investigator's judgment.
• Current or history of alcohol or drug abuse during the previous 3 years.
• Presence of tattoos that, in the opinion of the investigator, would preclude evaluation of the injection site.
• Volunteer registered in the French Health Ministry computerized file and not authorized to participate in a clinical trial.