This study will compare the two vaccines that have been developed to prevent and/or lessen the effects of shingles. One vaccine is live (Zostavax, licensed by FDA) and the other, herpes zoster subunit (HZ/su), contains a piece of the shingles virus (not live) and an ingredient that may enhance the body's immune response to the vaccine, and is currently investigational. The vaccines are being compared to assess their ability to stimulated protection against shingles. The study will provide an opportunity to determine the safety profile of each vaccine in a single trial. The study will also look at the effect of age on the immune response to the two vaccines and on the persistence of these responses.

160 people from the Denver area will participate. Duration is up to 5 years with 10-12 visits in that period. Subjects are randomized into one of 4 arms to receive either Zostavax or HZ/su. In this single blind study all subjects receive 2 injections: one at the first visit (Day 0) and the second at Day 60. HZ/su subjects will receive vaccine at both visits; Zostavax subjects will receive vaccine at the first visit and a placebo at the Day 60 visit. Blood is collected from all subjects at most visits. Some subjects spit into a tube for saliva collection. A urine sample is collected prior to vaccination if subject is a woman of childbearing potential. Subjects are asked to complete a diary to record any reactions in the 30 days after each injection. The Day 90 visit is the last one until the annual visits for blood draws begin at Day 365. Some subjects are also seen at Year 2 and Year 4; all subjects are seen at Year 5 for blood draw.

Inclusion Criteria:

• History of varicella or residence int he US for 30 years
• For Arms C and D - prior live zoster vaccine at least 5 years previously
• For Arms A and B - Age 50-59 or 70-85
• For Arms C and D - Age 70-85
• For women of childbearing potential, a negative pregnancy test and agreement to use adequate contraception from 30 days before until 3 months after the last dose of any study vaccine

Exclusion Criteria:

• History of herpes zoster
• For Arms A and B - prior live zoster vaccine
• Immune compromising illness or therapies or chronic illness
• Allergy to previous herpes zoster vaccine
• Other investigational drugs or vaccines within the past 6 months before the study and until last visit
• Blood products for 3 months prior to or planned during the study
• Concomitant non-topical antiviral therapy within 3 days prior to and 7 days after vaccination.
• Vaccines within 2 weeks (inactive vaccine) or 4 weeks (live vaccine) prior to the study until 30 days after any dose of either vaccine.
• Pregnancy or breast-feeding
• Current drug addiction or alcoholism.