HerpeVac Trial for Young Women

This study is a double-blind, randomized, controlled Phase III trial to assess the
prophylactic efficacy and safety of gD-Alum/MPL vaccine in the prevention of genital herpes
disease in young women who are herpes simplex virus (HSV)-1 and -2 seronegative. The primary
efficacy objective is to evaluate vaccine efficacy in the prevention of genital herpes
disease caused by HSV-1 and/or HSV-2 between months 2 and 20 in healthy adult women who were
initially HSV-1 and HSV-2 seronegative. The secondary efficacy objectives are to: evaluate
vaccine efficacy in the prevention of genital herpes disease caused by HSV-1 and/or HSV-2
occurring between the months 7 and 20; evaluate vaccine efficacy in the prevention of HSV-2
infection between months 2 and 20; and to evaluate vaccine efficacy in the prevention of
HSV-2 infection occurring between months 7 and 20. The study will enroll approximately 7,550
women, ages 18-30 years. Participants will be randomized to 1 of 2 possible study groups:
candidate vaccine; or control vaccine (hepatitis A vaccine). The study duration for each
subject will be approximately 20 months. Study procedures will include 9 scheduled study
visits (including the screening visit) and additional unscheduled visits for evaluation of
suspected herpes disease episodes. Three doses of vaccine or control will be administered
intramuscularly in the non-dominant deltoid on a 0, 1, and 6 month schedule. Subjects will
attend clinic visits at screening, months 2, 7, 12, 16, and 20. In subjects who present with
suspected herpes disease between months 17 and 20, an additional visit to collect a serum
sample will be scheduled 3 months after the evaluation for suspected genital herpes.

Inclusion Criteria:

- A female between, and including, 18 and 30 years of age at the time of the first
vaccination.

- Written informed consent obtained from the subject.

- Free of obvious health problems as established by medical history and clinical
examination before entering into the study.

- Seronegative for HSV-1 and HSV-2 by Western blot.

- Subject must be non-childbearing potential, i.e. either surgically sterilized or, if
of child bearing potential, she must be using a highly effective method of birth
control (e.g., intrauterine contraceptive device; oral contraceptives; diaphragm or
condom in combination with contraceptive jelly, cream or foam; Norplant®;
DepoProvera®; contraceptive skin patch or cervical ring) for 30 days prior to
vaccination, have a negative urine pregnancy test and must agree to continue such
precautions for two months after completion of the vaccination series.

- A subject for whom the investigator believes can and will comply with the requirements
of the protocol (e.g. completion of the memory aid/diary cards, return for follow-up
visits, accessible by phone or pager, able to self-sample and not planning on moving
from study area).

Exclusion Criteria:

- Pregnant or nursing female.

- Clinical signs or symptoms of current oro-labial, genital or non-genital HSV disease,
such as swelling, papules, vesicles, pustules, ulcers, crusts, fissures, erythema,
discharge, pain, burning, itching, tingling or dysuria.

- Previous vaccination against herpes.

- Previous administration of monophosphoryl lipid A (MPL) adjuvant (no vaccines
currently licensed in the USA contain this).

- History of any confirmed oro-labial, genital or non-genital HSV disease or infection.

- Use of any investigational or non-registered drug or vaccine other than the study
vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use
during the study period.

- Planned administration/ administration of a non-study vaccine within 30 days of the
first dose of the study vaccine with the following exceptions: Administration of
routine Meningococcal, Hepatitis B, inactivated Influenza, and Diphtheria/Tetanus
vaccine up to 8 days before the first dose of study vaccine is allowed.

- History of allergic disease or reactions likely to be exacerbated by any component of
the study vaccines, e.g. aluminum, MPL, alum-MPL, 2-phenoxyethanol or neomycin.

- Any confirmed or suspected immunosuppressive or immunodeficient condition including,
human immunodeficiency virus (HIV) infection.

- Acute or chronic, clinically significant (unresolved, requiring on-going medical
management or medication, etc.) pulmonary, cardiovascular, hepatic or renal function
abnormality, as determined by medical history or physical examination.

- Acute disease at the time of enrollment (defer vaccination until subject recovers).
Acute disease is defined as the presence of a moderate or severe illness with or
without fever. Study vaccine can be administered to persons with a minor illness such
as diarrhea, mild upper respiratory infection with or without low-grade febrile
illness.

- Oral temperature greater than or equal to 99.5º F (greater than or equal to 37.5º C) /
axillary temperature greater than or equal to 99.5º (greater than or equal to 37.5º C)
/ tympanic temperature on oral setting greater than or equal to 99.5º F (greater than
or equal to 37.5º C).

- Chronic administration (defined as more than 14 days) of immunosuppressants or other
immune-modifying drugs within six months prior to the first vaccine dose. (For
corticosteroids, this will mean prednisone or, equivalent, greater than or equal to
0.5 mg/kg/day. Inhaled or topical steroids are allowed.)

- Administration of immunoglobulins and/or any blood products within the three months
preceding the first dose of study vaccine or planned administration during the study
period.

- Recent history of chronic alcohol consumption (defined as more than 5 oz of ethanol
[absolute alcohol] per day) and/or drug abuse.

- History of sexually transmitted infection within 30 days preceding the first dose of
study vaccine.