Simplifying the Rabies Pre-exposure Vaccination
Condition: Rabies
MeSH terms: Rabies
Intervention: Human Diploid Cell Vaccine (HDCV) rabies vaccine
Intervention description: Human Diploid Cell Vaccine (HDCV) rabies Merieux 1 ml vaccine for rabies, provided by Sanofi-Pasteur, administered zvia ID route at two sites
Intervention MeSH terms: Vaccines
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 500.0
Sex: All
Minimum age: 18 Years
Maximum age: 47 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Rabies; Vaccination; Boostability

Summary:

      Rabies is a viral zoonosis that causes an encephalitis, almost invariably fatal. It is widely
      distributed across the globe: the World Health Organization (WHO) estimates that about 2,4
      billion people live in endemic areas for canine rabies. Vaccination of domestic animals is
      limited to industrialized and middle-income countries.

      The development of clinical rabies can be prevented through timely immunization after
      exposure: however, preventive vaccination simplifies the post-exposure procedure
      considerably, as immunoglobulins are no longer needed and less vaccine administrations are
      scheduled. Pre-exposure prophylaxis consists of an intramuscular (IM)of intradermal (ID) dose
      given on days 0, 7 and 21 or 28. The development of immunological memory after this
      vaccination is critical for the establishment of long lasting immunity. Subjects receiving a
      booster dose 1 year after pre-exposure prophylaxis segregate themselves into 'good' and
      'poor' responders; the former may not need further boosters for 10 years, whereas the latter
      may need more frequent boosters.

      Until recently, guidelines in travel medicine recommended pre-exposure vaccination only for
      some risk groups. Since recent studies have shown the effectiveness of the ID vaccination,
      the policies are changing towards pre-exposure vaccination for a larger population, including
      travelers to endemic regions, where immunoglobulins and vaccine are often not readily
      available.

      Based on the above, the investigators must stress the concept of "boostability" after a risk
      exposure. However, the current pre-exposure vaccination scheme could be improved: a schedule
      of 1 week would be less time consuming, would improve compliance and give less interference
      with other prophylaxis measures, e.g. mefloquine. Two small studies suggest that a schedule
      of 1 week interval is as effective and immunogenic as the standard one.

      The investigators will investigate whether the accelerated schedule is as effective as the
      classical schedule, by carrying out a randomized, non-inferiority study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willingness to provide written consent

          -  Seronegative for rabies

          -  Belgian soldiers who are deployable and visit the Travel clinic in Brussels during
             their preparation phase before deployment OR military students at the schools of
             Belgian Defense are eligible in preparation of an overseas exercise or during the
             scheduled vaccination program at the end of their studies

          -  Prepared to follow the study schedule

        Exclusion Criteria:

          -  Subjects who have had rabies vaccination (complete or incomplete) in the past due to
             post-exposure prophylaxis.

          -  Subjects with a known allergy to one of the components of the vaccine.

          -  Immune depressed persons or intake of immunodepressant medication.

          -  Subjects who take mefloquine

          -  Planned deployment to overseas areas within 35 days.