This is a Phase I, first-in-human, randomized, modified double-blind, active-controlled, dose-escalation study to assess the safety and immunogenicity of up to 3 dose levels of mRNA NA vaccines, administered as a single IM injection in healthy adults aged 18 years and older. Two age groups, 18 to 64 years and ≥65 years, will be included in this study.

This study will include a screening visit, 6 study visits occurring on Days 1, 3, 9, 29, 91, and 181, and a safety follow-up telephone call on Day 366.

Inclusion Criteria:

• Aged 18 years or older on the day of inclusion.

• A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:

  1. Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be postmenopausal for at least 1 year, or surgically sterile OR
  2. Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to study intervention administration until at least 12 weeks after study intervention administration

• A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 8 hours before administration of study intervention.

• Informed consent form has been signed and dated.

Exclusion Criteria:

• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
• Known systemic hypersensitivity to any of the study intervention components; history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances
• Moderate or severe acute illness/infection (according to investigator judgement) or febrile illness (temperature ≥100.4°F) on the day of study intervention administration.
• Have known or recently active (12 months) neoplastic disease or a history of any hematologic malignancy.
• Have any diagnosis, current or past, of autoimmune disease.
• Body mass index of 40 kg/m2 or higher.
• Receipt of immune globulins, blood, or blood-derived products in the past 3 months.
• Have taken high-dose inhaled corticosteroid (≥500 μg of fluticasone) within 6 months prior to study vaccination.
• Self-reported or documented seropositivity for HIV, hepatitis B virus, or hepatitis C virus.

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

This study will be blinded to participants, investigators/sub-investigators, outcomes assessors, laboratory personnel, and the sponsor study staff (with the exception noted for study staff involved in the ESDRs). Study staff involved in the ESDRs will be unblinded to group assignment of participants in the sentinel safety cohorts. After the ESDRs are performed for the sentinel safety cohorts, the SMT will continue monitoring the safety aspects of the study as part of blinded periodic safety reviews. Those preparing/administering the study interventions will be unblinded.