The Non-Specific Immunological Effects of Providing Oral Polio Vaccine to Seniors in Guinea-Bissau

Phase 4

• Conditions: Vaccine Reaction
• Interventions: Other: Placebo; Biological: Oral polio vaccine

• Registration Number: NCT06266754
• Lead Sponsor: Bandim Health Project

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.

Study Timeline

• Study First Submitted: 2024-01-18
• Study Start: 2024-01-29
• Status Verified: 2024-02
• Study First Submitted QC: 2024-02-11
• Last Update Submitted: 2024-02-11
• Study First Posted: 2024-02-20
• Last Update Posted: 2024-02-20
• Primary Completion: 2024-07-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: Male
• Target Recruitment: 80

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Saline, 2 drops on a sugar lump
Oral polio vaccine	Oral polio vaccine	Oral polio vaccine, 2 drops on a sugar lump

Primary Outcome Measures

Name	Time	Method
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/).
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/).

Trial Locations

Locations (1)

Bandim Health Project, Apartado 861; 🇬🇼 Bissau, Guinea-Bissau