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

NCT ID: NCT06266754

Last Updated: 2024-02-20

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-29
• Study Completion Date: 2024-12-31

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.

Conditions

Vaccine Reaction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Oral polio vaccine

Oral polio vaccine, 2 drops on a sugar lump

Group Type: EXPERIMENTAL

Oral polio vaccine

Intervention Type: BIOLOGICAL

Standard oral polio vaccine

Placebo

Saline, 2 drops on a sugar lump

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Saline 0.9%

Interventions

Oral polio vaccine

Standard oral polio vaccine

Intervention Type: BIOLOGICAL

Placebo

Saline 0.9%

Intervention Type: OTHER

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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

Bandim Health Project

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne Marie R Madsen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Bandim Health Project

Locations

Bandim Health Project, Apartado 861

Bissau, , Guinea-Bissau

Countries

Guinea-Bissau

Other Identifiers

OPV-IMMUNO-ADULT

Identifier Type: -

Identifier Source: org_study_id