This randomized, double-blind, placebo-controlled, non-inferiority crossover study will evaluate the Herpes Zoster Sunbit (HZ/su) vaccine in SLE patients in order to evaluate safety and immunogenicity in patients with variable baseline clinical activities, ages and immunosuppressant exposures. The investigators hypothesize that HZ/su administration will be non-inferior to placebo with respect to the risk of moderate or severe SLE flare(s) occurring within 24 weeks of receiving the first dose of the assigned treatment. In addition, the investigators hypothesize that immunogenicity of the vaccine in SLE patients will be at least 50% of levels observed in healthy subjects from prior large clinical trials.

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Female or male ≥18 years of age at the time of signing the informed consent
3. Meet the 2019 EULAR/ACR Classification Criteria for SLE
4. Female subjects must use 1 effective method of avoiding pregnancy, from the time they sign consent until end of the study period unless the subject is surgically sterile (e.g., bilateral oophorectomy or complete hysterectomy), has a sterile male partner, is at least 1 year postmenopausal, or practices sustained abstinence consistent with the subject's customary lifestyle. Postmenopausal is defined as at least 1 year since last menses and the subject has an elevated follicle-stimulating hormone (FSH) level greater than the threshold laboratory value of post-menopausal women at screening.

Exclusion Criteria:

1. Prior administration of the Herpes Zoster subunit vaccine (Shingrix) or the Varicella-Zoster virus vaccine live (Zostavax)
2. Clinical HZ infection within 12 months prior to screening or during screening
3. Hybrid SLEDAI >12 at screening visit
4. Presence of a mild, moderate, or severe flare per the rSFI at time of screenin
5. Increase in clinical SLEDAI parameters at time of enrollment relative to screening visit
6. Any vaccine, including the final/booster dose of any SARS-CoV-2 vaccine, within six weeks enrollment
7. Receipt of rituximab or cyclophosphamide within nine months of enrollment
8. Participation in an interventional clinical trial of SLE or other therapeutics within six months of enrollment
9. Moderate to severe infectious febrile illness or use of systemic antibiotics (antibacterial, antiviral, antifungal, or antiparasitic agent) within 4 weeks of enrollment
10. Are pregnant, nursing, or planning a pregnancy while enrolled in the study
11. Known primary or secondary immunodeficiency (malignancy, HIV, common variable immune deficiency) or medications used during cancer chemotherapy

The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: Amit Saxena (Amit.Saxena@nyulangone.org). The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.

The investigator who proposed to use the data will have access to the data upon reasonable request. Requests should be directed to Amit.Saxena@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.