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

Overview

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.

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.