The study plans to learn more about how the shingles vaccine, Shingrix (SRX), successfully prevents shingles in older people. Two vaccines are currently approved by the Food and Drug Administration (FDA) to prevent shingles. Zostavax is a live virus vaccine which has been available since 2006 and prevents shingles about 50% of the time, though it is less effective the older a person is when they receive it. Shingrix, which was approved by the FDA in 2017, is not a live virus, but has an additive in the vaccine to boost immune response. It is about 97% effective at preventing shingles regardless of a person's age and so far has been effective for at least 4 years after vaccination. Because Zostavax has live virus in it, giving a "challenge" dose of Zostavax - vOka varicella zoster virus - to people who have received both vaccines (Zostavax or Shingrix) in the past, will allow researchers to learn more about how the body works to prevent shingles and how any shingles vaccination helps protect against shingles.

The primary endpoint of this study was the area under the concentration/time curve of quantitative VZV DNA in plasma. However, all the VZV DNA measurements were below the lower limit of quantitation of the assay. Due to this unexpected outcome, we performed a qualitative analysis of presence or absence of VZV DNA in plasma at Day ≥3 after the vOka challenge.

Inclusion Criteria:

• Age 50-85
• General good health
• Women of non-childbearing potential must be postmenopausal or have undergone hysterectomy or bilateral oophorectomy
• ARM 1 ONLY: Documented evidence of immunization with ZVL or SRX at least 5 years previously
• ARM 2 ONLY; Documented evidence of immunization with ZVL 6-12 months prior to enrollment
• ARM 3 ONLY: Have never received any shingles vaccination

Exclusion Criteria:

• Prior history of herpes zoster (HZ)
• Blood products received in the 3 months prior to study enrollment or planned for the subsequent week for Arm 1; Arm 2 requires same exclusion; Arm 3 extends the exclusion to the week after the vOka challenge, which is 6 months after completing SRX administration.
• Significant immune suppressive illness or therapy
• Concomitant vaccine received within 2 (inactive) or 4 (live) weeks prior to the study or during the first week of the study.
• Women of childbearing potential.
• Pregnancy or breastfeeding.
• Participation in a concurrent clinical study in which the subject will be exposed to and investigational product during the period starting 7 days before the first dose of study vaccine through the completion of the study.

AEs starting within 7 days after injection and Grade ≥ 3 will be recorded and followed until resolution. ZVL - Subjects in Cohort 3 receiving ZVL on Day 0 will be followed for AEs for 7 days. RZV - Subjects in Cohort 4 receiving RZV on Day 0 and Day 60 will also be followed for AEs for 7 days after each injection. Any Grade ≥ 3 will be recorded and followed until resolution. All study procedure AEs will be followed until resolution.