Clinical trial NCT06266754: The Non-Specific Immunological Effects of Providing Oral Polio Vaccine to Seniors in Guinea-Bissau
Official title: The Non-Specific Immunological Effects of Providing Oral Polio Vaccine to Seniors in Guinea-Bissau
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE4
Conditions: Vaccine Reaction
Keywords: Oral polio vaccine
Trained immunity
Lead sponsor: Bandim Health Project
Sponsor class: OTHER
Collaborators: name: Radboud University Medical Center
First posted: 2024-02-20
Enrollment: 80
Sex: MALE
Minimum age (years): 50
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised trial
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 1 month after the intervention
measure: Levels of plasma markers of systemic inflammation such as TNF ligand superfamily member 12 (TWEAK) and sirtuin 2 (SIRT2)
timeFrame: 1 month after the intervention
measure: Amount of pseudo-bulk ATACseq and RNAseq - indicating chromatin accessibility of interferon-stimulated genes associated with the interferon response pathway in PBMCs.
timeFrame: 1 month after the intervention
measure: Proportions of immune cell subsets
timeFrame: 1 month after the intervention
Secondary outcomes:
Other outcomes:
Locations:
city: Bissau
country: Guinea-Bissau
facility: Bandim Health Project, Apartado 861
Study officials:
affiliation: Bandim Health Project
name: Anne Marie R Madsen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: