Utility of urinary cytokine levels as predictors of the immunogenicity and reactogenicity of AS01-adjuvanted hepatitis B vaccine in healthy adults

Abstract

Plasma cytokines are useful indicators of the inflammatory response to vaccination, and can serve as potential biomarkers of the systemic reactogenicity and immunogenicity of vaccines. Measurement of cytokines in urine may represent a non-invasive alternative to the blood-based markers. To evaluate whether urinary cytokine levels can help predict vaccine responses to an AS01B-adjuvanted vaccine, we measured concentrations of 24 cytokines in the urine from 30 hepatitis B virus (HBV)-naïve adults following administration of AS01B-adjuvanted HBV surface antigen vaccine (NCT01777295). Levels post-dose 2 were compared with the levels measured following a single placebo (saline) injection, which was administered 1 month before the first vaccination in the same participants. Urine was collected at eight timepoints before or up to 1 week following each treatment. Urinary concentrations were normalized to creatinine levels, and paired with previously reported, participant-matched plasma levels, local and systemic reactogenicity scores, and antibody response magnitudes. Of the urine cytokine panel, only few analytes were detectable: IL-8, IL-18 and IL-6 receptor, each showing no clear changes after vaccination as compared to placebo administration, and MCP-1 (CCL2) and IP-10 (CXCL10), which displayed in most participants transient surges post-vaccination. Urine levels did not correlate with the matched plasma levels. Interestingly, urinary IP-10 levels at 1 day post-second vaccination were significantly correlated (P = 0.023) with the concurrent intensity scores of systemic reactogenicity, though not with the local reactogenicity scores or peak antibody responses. No significant correlations were detected for MCP-1. Altogether, most urinary cytokines have limited utility as a proxy for plasma cytokines to help predict the inflammatory response, the immunogenicity or the reactogenicity of AS01B-adjuvanted vaccine, with the possible exception of IP-10. The utility of urinary IP-10 as a potential complementary biomarker of systemic vaccine reactogenicity needs substantiation in larger studies.

Keywords: AS01; Adjuvant; Cytokine; Reactogenicity; Urine; Vaccine.

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Wivine Burny reports financial support was provided by GSK group of companies. Caroline Herve reports financial support was provided by GSK group of companies. Magalie Caubet reports financial support was provided by GSK group of companies. Juan Pablo Yarzabal reports financial support was provided by GSK group of companies. Arnaud M Didierlaurent reports financial support was provided by GSK group of companies. Wivine Burny reports a relationship with GSK group of companies that includes: equity or stocks. Juan Pablo Yarzabal reports a relationship with GSK group of companies that includes: equity or stocks. Arnaud M Didierlaurent reports a relationship with GSK group of companies that includes: equity or stocks. Arnaud M Didierlaurent reports personal fees from Speranza and Lubrizol for consultancy, outside the submitted work]. All authors declare no other financial or non-financial relationships or activities.

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