A Phase 4 interventional study of Oral polio vaccine and Placebo in Vaccine Reaction, sponsored by Bandim Health Project. Enrolling by invitation at 1 site in Guinea-Bissau. Open to male participants aged 50 Years to 120 Years. Per ClinicalTrials.gov, last updated 2024-02-20.
Sponsored by Bandim Health Project · Phase 4, Interventional, and Prevention
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.
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
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.
Exclusion Criteria:
Oral polio vaccine, 2 drops on a sugar lump
Biological: Oral polio vaccine
Saline, 2 drops on a sugar lump
Other: Placebo
Standard oral polio vaccine
Saline 0.9%
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
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/).
Time frame: 1 month after the intervention
Levels of plasma markers of systemic inflammation such as TNF ligand superfamily member 12 (TWEAK) and sirtuin 2 (SIRT2)
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/).
Time frame: 1 month after the intervention
Amount of pseudo-bulk ATACseq and RNAseq - indicating chromatin accessibility of interferon-stimulated genes associated with the interferon response pathway in PBMCs.
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/).
Time frame: 1 month after the intervention
Proportions of immune cell subsets
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/).
Time frame: 1 month after the intervention
Plan to share: No — We collect sensitive data that cannot immediately be shared.
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