Training the Innate Immune System Against SARS-CoV-2 (COVID-19) Using the Shingrix Vaccine in Nursing Home Residents
Condition: Herpes Zoster; Allergy and Immunology; Corona Virus Infection
MeSH terms: Virus Diseases; Herpes Zoster; Coronavirus Infections
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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: 
      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.
    

Intervention name(s): SHINGRIX (Zoster Vaccine REcombinant, Adjuvanted); Normal Saline
Intervention type(s): Biological; Drug
Intervention description(s): 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.; Sterile normal saline, inactive control.
Other intervention name(s): Zoster Vaccine Recombinant, Adjuvanted; saline
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Herpes Zoster; corona virus infection; allergy and immunology