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

NCT06266754 | Enrolling By Invitation Phase 4

• 1 other identifier: OPV-IMMUNO-ADULT
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Vaccine Reaction

Keywords

Oral polio vaccine; Trained immunity

Outcome Measures

Primary Outcomes (4)

• 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/).

  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/).

  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/).

  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/).

  1 month after the intervention

Study Arms (2)

Oral polio vaccine

EXPERIMENTAL

Oral polio vaccine, 2 drops on a sugar lump

Biological: Oral polio vaccine

Placebo

PLACEBO COMPARATOR

Saline, 2 drops on a sugar lump

Other: Placebo

Interventions

Oral polio vaccine BIOLOGICAL

Standard oral polio vaccine

Oral polio vaccine

Placebo OTHER

Saline 0.9%

Placebo

Eligibility Criteria

• Age: 50 Years - 120 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Previous adverse events to OPV
• Suspicion of active viral/bacterial/HIV infection.

Sponsors & Collaborators

• Bandim Health Project: lead
• Radboud University Medical Center: collaborator

Study Sites (1)

Bandim Health Project, Apartado 861

Bissau, Guinea-Bissau

Location

MeSH Terms

Interventions

Poliovirus Vaccine, Oral

Intervention Hierarchy (Ancestors)

Poliovirus Vaccines; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Anne Marie R Madsen, MD, PhD

  Bandim Health Project

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: A placebo will be used.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised trial

Study Record Dates

• First Submitted: January 18, 2024
• First Posted: February 20, 2024
• Study Start: January 29, 2024
• Primary Completion: July 31, 2024
• Study Completion: December 31, 2024
• Last Updated: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

GU (1)