Enhancing Innate Anti-Viral Resistance Through A Community-Based Intervention - Generation Xchange (GenX)

This randomized controlled trial will test whether a recently developed community-based intergenerational mentoring program known as Generation Xchange (GenX) can enhance antiviral resistance in older African-American women and men in a low-SES urban community. Additional studies will identify the biological processes that promote resistance to respiratory virus infections and viral disease in older African-American women and men.

This randomized controlled intervention trial (planned n=160) will test whether participation in the Generation Xchange (GenX) intergenerational mentoring program can reduces vulnerability to respiratory virus infections (COVID, influenzas, colds), increase antiviral immune activity (Type I interferon responses), and reduce inflammatory immune activity in older African-American women and men living in a socioeconomically disadvantaged urban community. Blood samples will also be collected to determine which biological factors are most important in protecting older African-Americans from respiratory virus infection, and which of those factors is affected by the GenX intervention.

All data collected, assayed, coded, and analyzed by researchers blind to study condition and participant identity

Participants engage in parallel training/educational activities, and subsequently commence GenX program activity after 3 months

GenX trains older adults to collaborate with K-3rd grade teachers in mentoring high-need elementary school students in core reading and math skills.

Blood cell production of Type I interferon activity will stimulated by exposure to a fixed dose of model viral protein (TruCulture Resiquimod R848 tubes) and quantifying Type I interferon concentration in the cell culture supernatant fluid using the standard Armstrong bioassay (Armstrong, J.A. Cytopathic effect inhibition assay for interferon: microculture plate assay. Methods in enzymology 78, 381-387 (1981).) Antiviral activity is quantified as International Units of Interferon activity / mL.

Respiratory virus infection (cold, influenza, COVID) will be assessed by multiplex IgG serological assay (MesoScale Discovery V-PLEX COVID-19 Respiratory Panel 2; https://www.mesoscale.com/products/covid-19-respiratory-panel-2-igg-k15372u/). Concentrations are quantified as WHO international Binding Antibody Units / mL.

Blood plasma and blood cell culture supernatant fluids will be assayed for expression of pro-inflammatory cytokines (e.g., IL1B, IL6, TNF) using the MesoScale Discovery U-PLEX Macrophage M1 Combo 1 hu assay (https://www.mesoscale.com/products/u-plex-macrophage-m1-combo-1-human-k15336k/). Measurement units are pg of cytokine / mL.

Levels of key antiviral immune cells (e.g., dendritic cells, CD8+ T cells, etc.) will be assessed in blood samples by flow cytometry

Inclusion Criteria: Participating in the GenX intergenerational mentoring program All GenX mentors > 50 years of age are eligible to participate in this research GenX program participation requires: Reside in neighborhood of GenX schools (South-Central Los Angeles) Pass basic literacy and cognitive function tests Exclusion Criteria: Any health condition that would put participant at risk by enrollment/participation

Seeman T, Merkin SS, Goldwater D, Cole SW. Intergenerational mentoring, eudaimonic well-being and gene regulation in older adults: A pilot study. Psychoneuroendocrinology. 2020 Jan;111:104468. doi: 10.1016/j.psyneuen.2019.104468. Epub 2019 Sep 27.