Early spatiotemporal evolution of the immune response elicited by adenovirus vector vaccination

As the first responders to immunological challenges, the innate immune system has the potential to shape and regulate the ensuing adaptive immune response. Many clinical studies evaluating the role of various innate populations in initiating vaccine-elicited immunity have been largely relegated to blood. It is also largely unknown how the immune response to vaccination is initiating and evolving at the earliest time points post-vaccination. We sought to investigate the spatiotemporal evolution of the earliest immune responses to intramuscular adenovirus serotype 26 (Ad26) vector vaccination in blood and tissues. Using transcriptomic profiling, we show that Ad26 vector vaccination elicits broad transcriptomic changes as early as 1 hour post-vaccination across blood and tissues marked by IL-1, TNF-α, and IL-6 pro-inflammatory pathways. Immunologic data reveals an influx of Ly6C+ myeloid cells into muscle by 1 hour post-vaccination. A Ly6C+CD64+ population emerges in muscle and subsequently in the draining lymph node, suggesting that myeloid cells may be significant drivers of vaccine-elicited immune responses following intramuscular vaccination. Moreover, levels of IL-6, MIG, MIP-1α, and MIP-1β measured in serum at 6 hours post-vaccination positively correlated with the frequency of vaccine-elicited CD8+ T cell responses evaluated at 60 days post-vaccination. Taken together, our data suggests that the immune response to Ad26 vector vaccination commences by 1 hour across compartments and that events at as early as 6 hours post-vaccination can shape vaccine-elicited CD8+ T cell responses at memory time points.