Adjuvant AS01 activates human monocytes for costimulation and systemic inflammation

Background: The adjuvanted recombinant zoster vaccine (RZV) is highly effective even in adults over 80 years old. The high efficacy of RZV is attributed to its highly reactogenic adjuvant, AS01, but limited studies have been done on AS01's activation of human immune cells. Methods: We stimulated peripheral blood mononuclear cells (PBMC) with AS01 and used flow cytometry and RNA Sequencing (RNAseq) to analyze the impacts on human primary cells. Results: We found that incubation of PBMC with AS01 activated monocytes to a greater extent than any other cell population, including dendritic cells. Both classical and non-classical monocytes demonstrated this activation. RNASeq showed that TNF-alpha and IL1R pathways were highly upregulated in response to AS01 exposure, even in older adults. Conclusions: In a PBMC co-culture, AS01 strongly activates human monocytes to upregulate costimulation markers and induce cytokines that mediate systemic inflammation. Understanding AS01's impacts on human cells opens possibilities to further address the reduced vaccine response associated with aging.