Training the Innate Immune System Against SARS-CoV-2 (COVID-19) Using the Shingrix Vaccine in Nursing Home Residents

Study Overview
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Brief Summary
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The purpose of this study is to measure the effect of the Shingrix vaccine on your immune system and whether that has any effect on the body's ability to fight off other infections such as COVID-19. We hypothesize that: H1: Shingrix vaccination will elevate acute and trained immunity H2: For 6 months following the first injection, increased levels of acute and trained immunity is associated with less disease, including fewer hospitalizations and deaths associated with flu, pneumonia, and COVID-19.

Detailed Description
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The purpose of this pilot study is to provide preliminary data in support of the concept that training of the innate immune system occurs following immunization (2 doses ,3 months apart) with the Shingrix vaccine as compared to placebo (normal saline) in older adults residing in nursing homes. Two hundred nursing home residents, both men and women, aged >65 years, who have not acquired COVID-19 (verified through a screening questionnaire and by both viral antigen and antibody testing at the screen and least one week before the first injection) will get two intramuscular injections containing either the Shingrix vaccine, and the other half, two injections containing a normal saline (placebo comparison) approximately three months apart. Blood samples are collected before the baseline injection (day zero), 1 day after the second injection (91 days post) and 1 month following the second injection (120 days). Weekly symptom checks and monthly antibody testing around day 180- will identify residents with COVID-19 and the severity of COVID-19 symptoms. The primary outcome is the difference in immune cell capacity to produce type I interferon, interferon associated molecules, and proinflammatory mediators after receiving a 2 injection series of the Shingrix vaccine versus normal saline. Secondary outcomes include differences in hospitalization, pulmonary infections, and positive COVID-19 cases (via antibody testing on days 90, 120, and 180) in the Shingrix and normal saline groups. We anticipate that residents receiving the Shingrix vaccine will demonstrate signs of trained immunity compared to a control group receiving saline injections.

Official Title
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Training the Innate Immune System Against SARS-COV-2 (COVID-19) Using the Shingrix Vaccine in Nursing Home Residents: A Randomized, Doubled-Blinded, Comparative Group Observational Study

Conditions
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Herpes Zoster, Allergy and Immunology, Corona Virus Infection

Intervention / Treatment
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* Biological: SHINGRIX (Zoster Vaccine REcombinant, Adjuvanted)
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet Centers for Medicare and Medicaid definition for Long term care resident. 65 years and older. Have already received or provide consent to receive the 2020 flu vaccine. Negative screen (within the last 2 weeks) for COVID 19 virus. Has a history of chickenpox or shingles. Able to read and speak English. Able to provide informed consent and assent (with guardian/health care proxy). Exclusion Criteria: Brief Interview of Mental Status (BIMS) score <8 (indicating severe dementia). Prior vaccination with the Shingrix. Positive test for COVID 19 or prior history of COVID 19 infection. Conditions that confound the interpretation of the innate immune measures. (i.e. Terminal condition, receiving hospice, Stage 3 and 4 open wound, Chemotherapy, immune modulators or other immunosuppressants, autoimmune disorders, and BMI < 20 kg/m2). Conditions that confound interpretation of respiratory symptoms. (i.e Ventilator dependent, receiving more that 2-3 liters/min of oxygen by nasal cannula, chronic diarrhea, recurrent infections).

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two hundred nursing home residents, both men and women, aged >65 years, who have not acquired COVID-19 (verified through a screening questionnaire and by both viral antigen and antibody testing at the screen and least one week before the first injection) will get two intramuscular injections containing either the Shingrix vaccine, and the other half, two injections containing a normal saline (comparison) approximately two months apart. Blood samples are collected before the baseline injection (day zero), 1 day after the second injection (61 days post) and 1 month following the second injection (90 days). Weekly symptom checks and monthly antibody testing around day 180- will identify residents with COVID-19 and the severity of COVID-19 symptoms.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Shingrix<br>Shingrix Dosage: two .5 ml injections into the deltoid muscle, administered 3 months apart (Day 0 and Day 90). | Biological: SHINGRIX (Zoster Vaccine REcombinant, Adjuvanted)<br>* The Shingrix vaccine is a subunit vaccine that contains the recombinant varicella zoster virus (VZV) glycoprotein E (gE), adjuvanted with the proprietary Adjuvant System (AS01B). The AS01B Adjuvant system consists of two immune-stimulants, the saponin, Quillaja saponaria Molina, fraction 21 (QS21), and the toll-like receptor 4 (TLR4) agonist, MPL (3-O-desacyl-40-MPL) that enhance the release of interferon gamma (IFNϒ), which in turn stimulates activation and recruitment of blood monocyte-derived and resident lymph node dendritic cells to take up and present gE to cluster of differentiation 4 (CD4+) T cells.<br>* Other names: Zoster Vaccine Recombinant, Adjuvanted;|
| Placebo Comparator: Normal Saline<br>Sterile Normal Saline Solution, two .5 ml injections into the deltoid muscle, administered 3 months apart (Day 0 and Day 90) | Drug: Normal Saline<br>* Sterile normal saline, inactive control.<br>* Other names: saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidenced of active and trained innate immunity | The primary outcome is change in the release of Type I interferon, interferon gamma, interferon associated molecules, and proinflammatory mediators released from monocytes/macrophages and natural killer cells (including gene activation) after receiving 2 injections of the Shingrix vaccine versus normal saline. | Day 91 and 120 (post vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory Disease Severity (6 month) | cases ( nasal swab for viral antigen and antibody testing), symptoms (symptom checklist), hospitalizations (MDS 3.0 report/chart reviews) and deaths (MDS 3.0 report/chart reviews) associated with flu, pneumonia, and COVID-19. | Days 120 through 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Herpes Zoster, corona virus infection, allergy and immunology