Immunogenicity and Safety of a 1-dose Regimen of a Zoster Vaccine Versus Different 2-dose Regimens in Subjects ≥ 70 Years

• The 4 weeks post-dose 1 VZV antibody titres in group 1 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
• The VZV antibody titres individual fold rise from pre-vaccination to 4 weeks post-dose 1 in all groups and 4 weeks post-dose 2 in group 2 and in group 3 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
• The 12 months post-dose 1 VZV antibody titres in group 1 and the 12 months post-dose 2 VZV antibody titres in group 2 and in group 3 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• The VZV antibody titres individual fold rise from pre-vaccination to 12 months post-dose 1 in group 1 and from pre-vaccination to 12 months post-dose 2 in group 2 and in group 3 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• The 24 and 36 months post-dose 1 VZV antibody titres in group 1 and the 24 and 36 months post-dose 2 VZV antibody titres in group 2 and in group 3 [ Time Frame: 24 and 36 months ] [ Designated as safety issue: No ]
• The VZV antibody titres individual fold rise from pre-vaccination to 24 and 36 months post-dose 1 in group 1 and from pre-vaccination to 24 and 36 months post-dose 2 in group 2 and in group 3 [ Time Frame: 24 and 36 months ] [ Designated as safety issue: No ]
• Injection site erythema; Injection site swelling; Injection site pain [ Time Frame: Day 0 to Day 4 ] [ Designated as safety issue: Yes ]
• Unsolicited injection-site adverse reactions; Herpes zoster/ varicella/ zoster-like rash/ varicella-like rash; Other systemic adverse events; Any serious adverse events [ Time Frame: Day 0 to Day 28 following each vaccination ] [ Designated as safety issue: Yes ]
• Deaths; Vaccine-related serious adverse events; Herpes zoster/ zoster-like rash [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

• The 4 weeks post-dose 1 VZV antibody titres in group 1 [ Time Frame: 4 weeks ]
• The VZV antibody titres individual fold rise from pre-vaccination to 4 weeks post-dose 1 in all groups and 4 weeks post-dose 2 in group 2 and in group 3 [ Time Frame: 4 weeks ]
• The 12 months post-dose 1 VZV antibody titres in group 1 and the 12 months post-dose 2 VZV antibody titres in group 2 and in group 3 [ Time Frame: 1 year ]
• The VZV antibody titres individual fold rise from pre-vaccination to 12 months post-dose 1 in group 1 and from pre-vaccination to 12 months post-dose 2 in group 2 and in group 3 [ Time Frame: 1 year ]
• The 24 and 36 months post-dose 1 VZV antibody titres in group 1 and the 24 and 36 months post-dose 2 VZV antibody titres in group 2 and in group 3 [ Time Frame: 24 and 36 months ]
• The VZV antibody titres individual fold rise from pre-vaccination to 24 and 36 months post-dose 1 in group 1 and from pre-vaccination to 24 and 36 months post-dose 2 in group 2 and in group 3 [ Time Frame: 24 and 36 months ]
• Injection site erythema; Injection site swelling; Injection site pain [ Time Frame: Day 0 to Day 4 ]
• Unsolicited injection-site adverse reactions; Herpes zoster/ varicella/ zoster-like rash/ varicella-like rash; Other systemic adverse events; Any serious adverse events [ Time Frame: Day 0 to Day 28 following each vaccination ]
• Deaths; Vaccine-related serious adverse events; Herpes zoster/ zoster-like rash [ Time Frame: 3 years ]

Primary objective:

Immunogenicity To demonstrate that a second dose of ZOSTAVAX® elicits higher varicella-zoster virus (VZV) antibody titres than a first dose of ZOSTAVAX® whether given as a 0-1 month schedule or as a 0-3 month schedule in subjects ≥70 years of age as measured at 4 weeks post-vaccination

Secondary objectives Immunogenicity

• To summarise the VZV antibody titres at 4 weeks post-vaccination after a 1-dose regimen and 4 weeks post-vaccination after each dose of each 2-doses regimen of ZOSTAVAX®.
• To compare the VZV antibody titres at 12 months after completion of a 1-dose regimen with the VZV antibody titres at 12 months after completion of each 2-doses regimen of ZOSTAVAX®
• To summarise the VZV antibody titres at 24 and 36 months after completion of a 1-dose regimen and at 24 and 36 months after completion of each 2-doses regimen of ZOSTAVAX®

• Biological: Zostavax
  One dose (0.65 mL)
• Biological: Zostavax
  Two doses (0.65 mL) at one month interval
• Biological: Zostavax
  Two doses (0.65 mL) at 3 months interval

• Active Comparator: 1
  Intervention: Biological: Zostavax
• Experimental: 2
  Intervention: Biological: Zostavax
• Experimental: 3
  Intervention: Biological: Zostavax

Inclusion Criteria:

1. Age ≥ 70 years
2. Varicella history-positive or residence for > 30 years in a country with endemic VZV infection
3. Signed informed consent form prior to any study procedure

Exclusion Criteria:

1. Febrile illness within the last 72 hours before the first vaccination
2. Prior herpes-zoster episode clinically diagnosed by a physician
3. Prior receipt of varicella or zoster vaccine
4. Exposure to varicella or herpes-zoster within the 4 weeks prior to the first vaccination
5. Significant underlying illness preventing completion of the study vaccination schedules,
6. Known active tuberculosis,
7. Immune deficiency disorder, including active neoplastic disease within the prior 5 years,
8. Immune function impairment caused by medical condition or immunosuppressive therapy, or any other cause,
9. Receipt of any inactivated vaccine within the 2 weeks prior to the first vaccination,
10. Receipt of any other live vaccine within the 4 weeks prior to the first vaccination,
11. Receipt of immunoglobulins or blood-derived products within the 5 months prior to the first vaccination,
12. Concomitant use of non-topical antiviral therapy