This is a randomized, active-controlled, observer-blinded, dose-escalation multi-center trial of 2 doses of an investigational HZ vaccine (Z-1018) in approximately 764 healthy adults.

Part 1 will enroll approximately 440 participants 50 through 69 years of age (YOA) [inclusive] to 1 of 10 arms of Z-1018 or to Shingrix.

Part 2 will enroll approximately 324 participants ≥ 70 YOA to 1 arm of Z-1018 (selected from Part 1) to be administered in a 1:1 randomization ratio with Shingrix. Part 2 only: after completing the 12-month post-vaccination visit, Part 2 participants will be followed for an additional 4 years for immunopersistence and for herpes zoster (HZ) and post herpetic neuralgia (PHN).

Inclusion Criteria:

1. Willing to participate; informed consent provided for the study
2. Male or female ≥ 50 years of age (Part 1: 50 through 69 years of age, inclusive; Part 2: ≥ 70 years of age
3. In good health in the opinion of the investigator, based upon medical history, physical examination, and laboratory evaluation
4. Able to comprehend and follow all required trial procedures and be available for all visits scheduled in the trial
5. Seronegative for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) as assessed during Screening
6. If female of child-bearing potential and heterosexually active, has practiced adequate contraception for at least 28 days prior to vaccination, has negative pregnancy tests just prior to vaccination, and has agreed to continue adequate contraception through 3 months following the final study injection.

Exclusion Criteria:

1. History of HZ

2. Previous vaccination against varicella (chicken pox) or HZ

3. Febrile illness within 7 days of the first trial injection (defined as at least 1 measured body temperature of ≥ 38°C, regardless of route of measurement)

4. Confirmed SARS-CoV-2/COVID-19 infection as assessed during Screening within 7 days of first trial injection.

5. If female of childbearing potential, is pregnant (known before or established at the time of screening), breastfeeding, or planning a pregnancy or to breastfeed

6. Known or suspected immunodeficiency (including but not limited to HIV/AIDS), or immunocompromised state, as assessed by medical history, past or current laboratory studies, and/or physical examination

7. History of sensitivity to any component of the trial vaccines

8. Has received the following prior to Day 1 trial injection:

   a) ≤ 14 days: i) Any licensed or authorized inactivated vaccines (including vaccines containing mRNA or CpG)

   b) ≤ 28 days: i) Any live vaccine ii) Systemic corticosteroids (≥ 20 mg/ day of prednisone or equivalent for more than 14 consecutive days) or other immunomodulators or immune suppressive medication, with the exception of inhaled steroids iii) Any investigational medicinal agent

   c) ≤ 90 days: i) Granulocyte or granulocyte-macrophage colony-stimulating factor ii) Immunoglobulins or any blood products (receipt of certain monoclonal antibodies may on a case-by-case basis be non-exclusionary if approved via consultation with Sponsor Medical Monitor) iii) Antisense oligonucleotides iv) Drugs/investigational agents with very long half-lives (defined as ≥ 60 days) (eg, radioactive iodine-125, amiodarone, nirsevimab, and evinacumab) v) Infusion of blood products

   d) ≤ 6 months before Day 1 (or likely to require during the trial period): i) chronic administration of immunosuppressants or other immune-modifying drugs

   e) At any time: DNA plasmids or other genetic therapy intended to integrate permanently into host cells

9. Is undergoing chemotherapy or expected to receive chemotherapy during the trial period; and/or has a diagnosis of cancer within the last 5 years other than squamous cell or basal cell carcinoma of the skin

10. History or current evidence of any condition, therapy, laboratory abnormality, or other finding that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

11. Underlying chronic medical condition requiring ongoing follow-up and monitoring by a healthcare provider that might affect the immune response to vaccine (eg, diabetes mellitus, chronic kidney disease)

12. Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial

13. Current or historical autoimmune disease

14. Any skin condition and/or tattoo on both arms that may interfere with the evaluation of safety at the injection site, in the opinion of the treating investigator

15. Any other finding that the Investigator considers will make the participant unsuitable for the trial or unable to comply with the trial requirements