Effect of Antimalarial Drugs to Rabies Vaccine for Post-exposure Prophylaxis.

Rabies is present on all continents where U.S. military personnel deploy, including countries
where malaria is also endemic and where U.S. military personnel are required to take malaria
prophylaxis. Rabies post-exposure prophylaxis in unvaccinated individuals who are not on
malaria prophylaxis consists of four, 1.0-mL intramuscular (IM) injections of the purified
chick embryo cell (PCECV) rabies vaccine on days 0, 3, 7, and 14. The current Advisory
Committee on Immunization Practices (ACIP) guidelines recommend that exposed persons who are
taking malaria prophylaxis should receive a fifth dose of rabies vaccine 28 days after the
exposure. These guidelines do not differentiate between drugs used for malaria prophylaxis
This study will administer the post-exposure regimen to volunteers from a US population of
military age who are taking one of three malaria prophylaxis regimens or no malaria
prophylaxis. The goal of this study is to asses if individuals on malaria prophylaxis achieve
the required rabies titer after completion of the four dose regimen.

Obtaining rabies vaccine and rabies immune globulin in a deployed setting can be challenging.
A full understanding of the requirements for protecting exposed individuals is necessary for
appropriate decision making in a resource-constrained environment.

Inclusion Criteria:

1. Provide signed and dated informed consent form.

2. Willing to comply with all study procedures and be available for the duration of the
study.

3. Male or female, aged ≥ 18 to ≤ 60 years on day of inclusion.

4. In good general health based on medical history and physical exam

Exclusion Criteria:

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
last vaccination.

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 are well controlled are not exclusion
criteria.

6. Use of any immunosuppressive drug at the time of the study or 30 days previously.
Topical steroids will not be considered an immunosuppressive drug and their use will
not be considered an exclusion criteria.

7. Any immunosuppressive disorder, such as HIV infection, common variable
immunodeficiency, active cancers or chemotherapy.

8. History of renal insufficiency or requiring dialysis.

9. Have 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.

10. 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.

11. Previous adverse reaction to any of the antimalarial drugs used in this study.

Temporary Exclusion Criteria: Moderate or severe acute illness/infection (according to
investigator judgment) or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) on day 0.. A
prospective subject should not be included in the study until the condition has resolved or
the febrile event has subsided. If the delay for the febrile illness exceeds the window
between screening and vaccination, or if deemed necessary by the investigator, a
prospective subject may be re-screened once the fever has resolved.

Recent or scheduled receipt of any vaccine 4 weeks prior to day 0.