• Number of participants reporting solicited injection site reactions and systemic reactions [ Time Frame: Within 7 days after any vaccination ]
  Injection site reactions: pain, erythema, and swelling Systemic reactions: fever, headache, malaise and myalgia
• Number of participants reporting immediate adverse events (AEs) [ Time Frame: Within 30 minutes after each vaccination ]
  Medically relevant unsolicited systemic AEs, including those related to the product administered
• Number of participants reporting unsolicited injection site reactions and systemic AEs [ Time Frame: Within 28 days after each vaccination ]
  Injection site reaction: adverse reaction at and around the injection site considered to be related to the product administered Systemic AEs: systemic manifestations not associated with the vaccination or administration site
• Number of participants reporting serious adverse events (SAEs) [ Time Frame: Up to 6 months after last vaccination ]
  SAEs, including adverse event of special interest (AESIs)
• Geometric mean titers (GMTs) of RVNA [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 ]
  RVNA titer will be measured by RFFIT assay
• Percentage of participants achieving RVNA Titer ≥ 0.5 IU/mL [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 ]
  RVNA titer will be measured by RFFIT assay
• Percentage of participants with RVNA titer ≥ lower limit of quantitation (LLOQ) [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 ]
  RVNA titer will be measured by RFFIT assay LLOQ for RFFIT assay is 0.2 IU/mL
• Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 ]
  RVNA titer will be measured by RFFIT assay
• Percentage of participants with complete or incomplete virus neutralization [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 ]
  Virus neutralization is defined as complete (absence of fluorescent cells) or incomplete (presence of fluorescent cells) at the participant/timepoint level at the starting dilution (1/5) of RFFIT assay

• Percentage of participants reporting solicited injection site reactions and systemic reactions [ Time Frame: Within 7 days post-vaccination ]
  Injection site reactions: pain, erythema, and swelling Systemic reactions: fever, headache, malaise and myalgia
• Number of participants reporting immediate adverse events (AEs) [ Time Frame: Within 30 minutes post-vaccination ]
  Medically relevant unsolicited systemic AEs, including those related to the product administered
• Number of participants reporting unsolicited injection site reactions and systemic AEs [ Time Frame: Within 28 days post-vaccination ]
  Injection site reaction: adverse reaction at and around the injection site considered to be related to the product administered Systemic AEs: systemic manifestations not associated with the vaccination or administration site
• Number of participants reporting serious adverse events (SAEs) [ Time Frame: Up to 6 months post-vaccination ]
  SAEs, including adverse event of special interest (AESIs)
• Geometric mean titers (GMTs) of RVNA [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 (post-vaccination) ]
  RVNA titer will be measured by RFFIT assay
• Percentage of participants achieving RVNA Titer ≥ 0.5 IU/mL [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 (post-vaccination) ]
  RVNA titer will be measured by RFFIT assay
• Percentage of participants with RVNA titer ≥ lower limit of quantitation (LLOQ) [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 (post-vaccination) ]
  RVNA titer will be measured by RFFIT assay LLOQ for RFFIT assay is 0.2 IU/mL
• Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 (post-vaccination) ]
  RVNA titer will be measured by RFFIT assay
• Percentage of participants with complete or incomplete virus neutralization [ Time Frame: Day 0 (pre-vaccination), Day 14, Day 28 and Day 42 (post-vaccination) ]
  Virus neutralization is defined as complete (absence of fluorescent cells) or incomplete (presence of fluorescent cells) at the participant/timepoint level at the starting dilution (1/5) of RFFIT assay

Primary Objective:

To demonstrate that Purified Vero Rabies Vaccine - Serum Free Vaccine generation 2 (VRVg-2) is non-inferior to Verorab and Imovax Rabies vaccines when co-administered with human rabies immunoglobulin (HRIG), in terms of proportion of subjects achieving a rabies virus neutralizing antibody (RVNA) titer ≥ 0.5 IU/mL at D28, ie, 14 days after the fourth vaccine injection.

Secondary Objective:

• To describe the safety profile of VRVg-2 versus Verorab and Imovax Rabies vaccines when co-administered with HRIG, as well as that of VRVg-2, after each vaccine injection.
• To demonstrate that the proportion of subjects in the VRVg-2 + HRIG group achieving an RVNA titer ≥ 0.5 IU/mL at D28 is at least 95%.
• To describe the immune response induced by VRVg-2 versus Verorab and Imovax Rabies vaccines when co-administered with HRIG, as well as that induced by VRVg-2, at D14 (7 days after the third injection), at D28 (14 days after the fourth injection) and at D42 (14 days after the last injection).

• Biological: VRVg-2

  Pharmaceutical form:Powder and solvent for suspension for injection

  Route of administration: Intramuscular

• Biological: Purified Vero Rabies Vaccine

  Pharmaceutical form:Powder and solvent for suspension for injection

  Route of administration: Intramuscular

  Other Name: Verorab®
• Biological: Human Diploid Cell Vaccine (HDCV)

  Pharmaceutical form:Powder and solvent for suspension for injection

  Route of administration: Intramuscular

  Other Name: IMOVAX® Rabies
• Biological: Rabies immune globulin (human)

  Pharmaceutical form:Solution for injection

  Route of administration: Intramuscular

  Other Name: IMOGAM® Rabies-HT

• Experimental: Group 1: VRVg-2 + HRIG
  VRVg-2 5 injections at Day 0, Day 3, Day 7, Day 14 and Day 28 + Human Rabies Immunoglobulins (HRIG) single injection at Day 0
  Interventions:

  • Biological: VRVg-2
  • Biological: Rabies immune globulin (human)
• Active Comparator: Group 2: Verorab + HRIG
  Verorab 5 injections at Day 0, Day 3, Day 7, Day 14 and Day 28 + HRIG single injection at Day 0
  Interventions:

  • Biological: Purified Vero Rabies Vaccine
  • Biological: Rabies immune globulin (human)
• Active Comparator: Group 3: Imovax Rabies + HRIG
  Imovax Rabies 5 injections at Day 0, Day 3, Day 7, Day 14 and Day 28 + HRIG single injection at Day 0
  Interventions:

  • Biological: Human Diploid Cell Vaccine (HDCV)
  • Biological: Rabies immune globulin (human)
• Experimental: Group 4: VRVg-2
  VRVg-2 5 injections at Day 0, Day 3, Day 7, Day 14 and Day 28
  Intervention: Biological: VRVg-2

Inclusion criteria :

• Men or women aged ≥18 years on the day of inclusion (≥ 18 years means from the day of the 18th birthday onwards, with no upper age limit).
• Able to attend all scheduled visits and to comply with all trial procedures.
• Body Mass Index (BMI): 18.5 Kg/m2 ≤ BMI ≤ 30 Kg/m2.

Exclusion criteria:

• Pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, or surgically sterile.
• Participation at the time of study enrollment or, planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
• Receipt of any vaccine in the 4 weeks (28 days) preceding the first trial vaccination or planned receipt of any vaccine prior to Visit 7.
• Previous vaccination against rabies (in pre- or post-exposure regimen) with either the trial vaccines or another vaccine.
• Receipt of immune globulins, blood or blood-derived products in the past 3 months.
• 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).
• At high risk for rabies exposure during the trial (veterinarians and their staff, animal handlers, rabies researchers, and certain laboratory workers, persons whose activities bring them into frequent contact with rabies virus or potentially rabid bats, raccoons, skunks, cats, dogs, or other species at risk for having rabies, people travelling where rabies is enzootic).
• Known systemic hypersensitivity to any of the vaccine or HRIG components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances.
• Self-reported thrombocytopenia, contraindicating intramuscular (IM) vaccination.
• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination.
• Current alcohol or substance abuse that, in the opinion of the investigator, might interfere with the trial conduct of completion.
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
• Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0 C). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
• Personal history of Guillain-Barré syndrome.
• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.