Responses to Rabies Vaccine in Adults With or Without Antibiotics
Condition: Rabies Human
MeSH terms: Rabies
Intervention: Rabies Vaccine; Metronidazole; Vancomycin; Neomycin Sulfate
Intervention description: A 1.0 milliliter (mL) dose of Imovax® will be given to participants on Day 0 and Day 28 of the study.; The antibiotic regimen will be given for five days beginning 3 days prior to vaccination, on the vaccination day, and one day after vaccination for a total for 5. The regimen will include 500 milligrams (mg) of Flagyl taken by mouth three times a day.; The antibiotic regimen will be given for five days beginning 3 days prior to vaccination, on the vaccination day, and one day after vaccination for a total for 5. The regimen will include 125 mg of Vancocin taken by mouth four times a day.; The antibiotic regimen will be given for five days beginning 3 days prior to vaccination, on the vaccination day, and one day after vaccination for a total for 5. The regimen will include 500 milligrams (mg) of Neomycin sulfate taken by mouth three times a day.
Intervention MeSH terms: Metronidazole; Vancomycin; Neomycin
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Longitudinal and Randomized
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Rabies Vaccine; Antibiotics; Biopsy

Summary:

      The use of antibiotics changes micro-organisms in the intestines which may impact the body's
      vaccine immune response and alter the effectiveness of the rabies vaccine.

      There will be two randomized groups (1:1 randomization). Group A will start taking an
      antibiotic regimen by mouth 3 days prior to vaccination and continue taking antibiotics the
      day of rabies vaccination and one day after vaccination for a total of 5 days. Group B will
      only receive the rabies vaccination and will not take any antibiotics. The dosage of each
      antibiotic is taken from their respective package inserts and does not exceed the maximum
      dose allowed for each antibiotic.

      The purpose of the study is to look at immune response after rabies vaccination with or
      without the use of antibiotics from day of vaccination to 28 days post vaccination in both
      groups.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy individuals aged 18-49 years.

          -  Able to understand and give informed consent.

          -  Women of child-bearing potential (not surgically sterile via tubal ligation, bilateral
             oophorectomy or hysterectomy or who are not postmenopausal for ≥1 year) must agree to
             practice adequate contraception that may include, but is not limited to, abstinence,
             monogamous relationship with vasectomized partner, barrier methods such as condoms,
             diaphragms, spermicides, intrauterine devices, and licensed hormonal methods for 28
             days before and 28 days after Rabies vaccination.

        Exclusion Criteria:

          -  Receipt of the following:

               -  Receipt of blood products 3 months prior to vaccination or expected receipt
                  through 12 months after vaccination.

               -  Receipt of any live virus vaccines within 28 days prior to vaccination or
                  expected receipt within 28 days after vaccination.

               -  Receipt of any inactivated vaccine within 14 days or expected receipt within 14
                  days after vaccination.

               -  Receipt of any antibiotic 3 months prior to vaccination or expected receipt 28
                  days after vaccination.

               -  Receipt of probiotics and prebiotics 3 months prior to vaccination or expected
                  receipt 28 days after vaccination.

               -  Receipt of proton pump inhibitors, H2 receptor blockers, or antacids 3 months
                  prior to vaccination or expected receipt 28 days after vaccination.

          -  Presence of co-morbidities or immunosuppressive states such as:

               -  Chronic medical problems including (but not limited to) insulin dependent
                  diabetes, severe heart disease (including arrhythmias), severe lung disease, auto
                  immune diseases, thrombocytopenia and grade 4 hypertension. Grade 4 hypertension
                  per CTCAE criteria is defined as Life-threatening consequences (e.g., malignant
                  hypertension, transient or permanent neurologic deficit, hypertensive).

               -  Chronic neurologic conditions including seizure disorder, Parkinson's disease,
                  myasthenia gravis, neuropathy, or history of encephalopathy, meningitis or
                  ototoxicity.

               -  Any history of gastrointestinal disease including (but not only): documented
                  bacterial gastroenteritis or gastroenteritis associated with fever or associated
                  with presence of blood/mucus in stools in the last 3 months, inflammatory bowel
                  disease, and/or gastrointestinal surgery.

               -  Any history of kidney or liver diseases.

               -  Alcohol abuse, drug abuse, or psychiatric conditions that in the opinion of the
                  investigator would preclude compliance with the trial or interpretation of safety
                  or endpoint data.

               -  Any history of lymphoma involving axillary nodes or any history of breast cancer.

               -  Impaired immune function or known chronic infections including, but not limited
                  to, known HIV, tuberculosis, hepatitis B or C; organ transplantation (bone
                  marrow, hematopoietic stem cell, or solid organ transplant); immunosuppression
                  due to cancer; current and/or expected receipt of chemotherapy, radiation
                  therapy, steroids (i.e., more than 20 mg of prednisone given daily or on
                  alternative days for 2 weeks or more in the past 90 days, or high dose inhaled
                  corticosteroids); and any other immunosuppressive therapies, functional or
                  anatomic asplenia, or congenital immunodeficiency. Subjects receiving > 20 mg/day
                  of prednisone or its equivalent daily or on alternate days for more than 2 weeks
                  may enter the study after therapy has been discontinued for more than 3 months
                  and Subjects are excluded if on high dose intranasal steroids defined as > 960
                  mcg/day of beclomethasone dipropionate or equivalent.

               -  Pregnancy or breast feeding

          -  Conditions that could affect the safety of the volunteers, such as:

               -  Severe reactions to prior vaccinations, including anaphylaxis

               -  History of Guillain-Barré syndrome

               -  History of bleeding disorders or current use of warfarin, aspirin, heparin,
                  nonsteroidal anti-inflammatory drugs (NSAIDs) or other blood
                  thinner/anticoagulant medications in the past week (for subjects undergoing lymph
                  node sampling)

               -  Use of anticonvulsants

               -  Use of digoxin or other forms of digitalis

               -  Any allergy to any component of the vaccine or lidocaine (for subjects undergoing
                  lymph node sampling)

               -  Allergy to vancomycin, metronidazole or neomycin as well as other aminoglycosides
                  (gentamicin, tobramycin, amikacin, streptomycin)

          -  Volunteers with any acute illness, including any fever within 3 days prior to
             vaccination.

          -  Social, occupational, or any other condition that in the opinion of the investigator
             might interfere with compliance with the study and vaccine evaluation.

          -  Positive C difficile testing by polymerase chain reaction (PCR) at screening or
             history of C difficile infection.

          -  Any grade 2 safety lab test results at screening

          -  Previously received any rabies vaccine or immunoglobulin.

          -  Are at high risk of exposure to rabies: veterinarians, animal handlers, rabies
             laboratory workers, spelunkers, frequent contact with rabies virus or with possibly
             rabid animals, international travelers who are likely to come in contact with animals
             in parts of the world where rabies is common, and rabies biologics production workers.

          -  Bilateral inflammatory process of upper arms in the past 2 weeks.

          -  Prior breast or axillary biopsy and/or surgery.