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

Vaccine Reaction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06266754
• Other study ID #: OPV-IMMUNO-ADULT
• Status: Enrolling by invitation
• Phase: Phase 4
• Start date: January 29, 2024
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: Bandim Health Project
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 80
• Est. completion date: December 31, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 50 Years to 120 Years

Eligibility

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.

Related Conditions & MeSH terms

• Vaccine Reaction

Intervention

Biological:
• Oral polio vaccine
Standard oral polio vaccine

Other:
• Placebo
Saline 0.9%

Locations

Country	Name	City	State
Guinea-Bissau	Bandim Health Project, Apartado 861	Bissau

Sponsors (2)

Lead Sponsor	Collaborator
Bandim Health Project	Radboud University Medical Center

Country where clinical trial is conducted

Guinea-Bissau, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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