The purpose of this study is to compare the effectiveness of a two dose versus a three dose
schedule and intramuscular versus intradermal injection for pre-exposure prophylaxis.
This is an exploratory vaccine trial to evaluate immunogenicity of a non-licensed dosing
schedule and route of administration for a currently FDA licensed rabies vaccine for
pre-exposure prophylaxis against rabies infection. The goal of this study is to characterize
the immune response and persistence of immunity to a shortened dose schedule and intradermal
(ID) administration, relative to the current licensed dosing schedule of the rabies vaccine
(3 dose (0, 7, 21 days) IM). Rabies virus is endemic throughout the world due to high rates
of both wild and domestic animal rabies and the risk to deployed military in endemic areas
is considerable. Currently the commonly supported pre-exposure prophylaxis regimen for
rabies, in the United States is comprised of three, 1.0 ml intramuscular (IM) injections of
the human diploid cell vaccine (HDCV) or purified chick embryo cell (PCEC) rabies vaccine on
days 0, 7, and 21 or 28. Modified, two and three dose schedules of intradermal (ID)
injections of 0.1 ml of HDCV and PCEC are utilized outside the US. These two and three dose
intradermal schedules share a similar safety and immunogenicity profile to intramuscular
vaccinations and are easily boosted at one year after vaccination. A death, from rabies, of
a US Soldier returned from Afghanistan underscores the importance of rabies pre-exposure
prophylaxis for soldiers and the need to evaluate the safest, most effective means of
vaccinating large deploying forces. While the current three dose, 1 ml IM rabies series is
effective, a shortened, equally effective vaccination series with significantly smaller dose
per injection would greatly improve the logistics and cost associated with universal or even
targeted coverage of deploying soldiers. Evaluation of a shorter, smaller-dose, pre-exposure
vaccination series for rabies is the goal of this study.
Male and non-pregnant females aged ≥ 18 to ≤ 60 years on the day of inclusion Able to
comprehend and give informed consent Able to attend all scheduled visits and to comply
with all trial procedures Subject in good health, based on medical history and physical
1. Subject is pregnant, or lactating, or of childbearing potential (to be considered of
non-childbearing potential, a female must be post- menopausal for at least 1 year,
surgically sterile, or using an effective method of contraception or abstinence from
at least 4 weeks prior to the first vaccination and until at least 4 weeks after the
2. Participation in the 4 weeks preceding the first trial vaccination, or planned
participation during the present trial period, in another clinical trial
investigating a vaccine, drug, medical device, or medical procedure.
3. Previous history of receiving the rabies vaccine.
4. Previous history of receiving rabies immune globulin.
5. Any major psychiatric disorder, such as severe depression, severe anxiety disorder,
psychosis, schizophrenia, other major psychiatric disorders, or seizures. History of
mild depression or anxiety disorder that is well controlled is not an exclusion
6. Any history of cardiac arrhythmias, such as: Bradycardia, tachycardia, heart block,
SVT, PAC, VF, VT, or any other conduction abnormalities.
7. Use of any immunosuppressive drug , including topical steroids of potency groups I,
II or III within 30 days of the study period.
8. Any immunosuppressive disorder, such as HIV, common variable, active cancers or
9. History of renal insufficiency or requiring dialysis.
10. Any condition that would, in the opinion of the site investigator, place the subject
at an unacceptable risk of injury or render the subject unable to meet the
requirements of the protocol.
11. Identified as an employee of the Investigator or study center, with direct
involvement in the proposed study or other studies under the direction of that
Investigator or study center, as well as family members (i.e., immediate, husband,
wife and their children, adopted or natural) of the employee or the Investigator.