Eliciting a potent long-lasting immune response (e.g. Ab, CD4, and CD8 T cells) against the SARS-CoV-2 virus with a vaccine will most likely be essential to reduce morbidity and mortality during future waves of viral propagation. To this end our lab has been working on a way to increase the potency of vaccines for 20 years through engagement of the TNF-receptor family member, OX40. This talk will cover the data generated over the last 20 years in vaccinated hosts boosted with OX40 agonists and present preliminary data in mice injected with a COVID-19 vaccine w/wo OX40 agonists.