Vaccine Reaction
Conditions
Keywords
Oral polio vaccine, Trained immunity
Brief summary
OPV is the live attenuated vaccine against polio virus. OPV has been key in almost eradicating polio infection. Intriguingly, OPV has been associated with lower all-cause mortality and morbidity. These beneficial OPV effects were seen in contexts with no circulating polio virus and thus have nothing to do with the specific effects of OPV against polio infection. They have been coined non-specific effects (NSEs). Such NSEs have also been observed for other live attenuated vaccines such as BCG vaccine and measles vaccine. The underlying immunological mechanisms are unknown. Other live vaccines with beneficial NSEs have been shown to induce epigenetic changes leading to trained immunity. They have also been associated with decreased inflammation. In the present study it will be investigates whether OPV can induce trained immunity, reduce inflammation, and induce epigenetic modifications of the innate immune cells in senior citizens in Guinea-Bissau.
Detailed description
The aim is to study the non-specific immunological effects of providing a single dose of OPV to seniors aged 50 and above in Guinea-Bissau: Hypotheses 1. OPV induces innate immune training (substudy A) 2. OPV is associated with reduced systemic inflammation (substudy A) 3. OPV induces epigenetic modifications of the innate immune cells (substudy B) Setting: Bandim Health Project (BHP)'s Health and Demographic Surveillance System (HDSS) in Bissau. Design: Individually randomized trial in BHP's study area. Participants will be randomized 1:1 to OPV or placebo. To limit the amount of blood drawn from one single participant, two substudies with similar design will be conducted, with two different outcomes. The outcomes of the two substudies will be as follows: Substudy A: Immunological impact of OPV. Study the stimulation of cytokine production by heterologous stimuli as a biomarker of trained immunity induction and circulating biomarkers as a mirror of systemic inflammation induced by OPV. Substudy B: Transcriptional and epigenetic reprogramming of immune cells by OPV. Study the transcriptional and epigenetic rewiring of immune cells induced by OPV by single-cell ATAC-Sequencing and RNA-Sequencing.
Interventions
BIOLOGICALOral polio vaccine
Standard oral polio vaccine
OTHERPlacebo
Saline 0.9%
Sponsors
Radboud University Medical Center
Bandim Health Project
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
A placebo will be used.
Intervention model description
Randomised trial
Eligibility
Sex/Gender
MALE
Age
50 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
* Male. * Living in a household which had a Bandim Health Project census visit conducted after 1 January 2017. * Age above 50. * Has a visible BCG scar.
Exclusion criteria
* Previous adverse events to OPV * Suspicion of active viral/bacterial/HIV infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Levels of in vitro proinflammatory cytokines such as IL1-beta, TNF-alfa and IFN-gamma after stimulation of peripheral blood mononuclear cells with non-OPV antigens and mitogens | 1 month after the intervention | Study the ability of cells of producing cytokines in vitro after heterologous stimuli. This is a well-established biomarker of trained immunity (ref: https://pubmed.ncbi.nlm.nih.gov/38198850/). |
| Levels of plasma markers of systemic inflammation such as TNF ligand superfamily member 12 (TWEAK) and sirtuin 2 (SIRT2) | 1 month after the intervention | Study the effect on systemic inflammation induced by OPV. Previous studies have shown that BCG reduce up to a third of proinflammatory proteins as a marker of non-specific effects of that vaccine, we will study if this is the case also for OPV (ref:https://pubmed.ncbi.nlm.nih.gov/32692728/). |
| Amount of pseudo-bulk ATACseq and RNAseq - indicating chromatin accessibility of interferon-stimulated genes associated with the interferon response pathway in PBMCs. | 1 month after the intervention | Study the epigenetic rewiring of immune cells induced by OPV by single-cell ATAC-Sequencing and whole-genome methylation assays. This is a new method to assess if there has been changes to the accessibility of the genes (ref: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022455/). |
| Proportions of immune cell subsets | 1 month after the intervention | Study the transcriptional effects of OPV on immune cell by studying the transcriptional rewiring of immune cells induced by OPV by single-cell RNA-Sequencing (ref: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022455/). |
Countries
Guinea-Bissau
Outcome results
None listed