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.
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.
Biological: SHINGRIX (Zoster Vaccine REcombinant, Adjuvanted)
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 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.
Other Name: Zoster Vaccine Recombinant, Adjuvanted
Drug: Normal Saline
Sterile normal saline, inactive control.
Other Name: saline
Inclusion Criteria:
1. Meet Centers for Medicare and Medicaid definition for Long term care resident.
2. 65 years and older.
3. Have already received or provide consent to receive the 2020 flu vaccine.
4. Negative screen (within the last 2 weeks) for COVID 19 virus.
5. Has a history of chickenpox or shingles.
6. Able to read and speak English.
7. Able to provide informed consent and assent (with guardian/health care proxy).
Exclusion Criteria:
1. Brief Interview of Mental Status (BIMS) score <8 (indicating severe dementia).
2. Prior vaccination with the Shingrix.
3. Positive test for COVID 19 or prior history of COVID 19 infection.
4. 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).
5. 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).
Fran and Earl Ziegler College of Nursing
Oklahoma City, Oklahoma, United States
Barbara W. Carlson, RN, Ph.D., Study Director
Professor, University of Oklahoma Health Sciences Center