Adjuvant associated peripheral-blood mRNA profiles and kinetics induced by the adjuvanted recombinant-protein candidate tuberculosis vaccine M72/AS01 in BCG-vaccinated adults

Systems biology has the potential to identify gene signatures associated with vaccine immunogenicity or protective efficacy. The main objective of our study was to identify optimal post-vaccination time points for evaluating blood RNA-expression profiles in recipients of the candidate tuberculosis vaccine M72/AS01. In this phase II open-label study (NCT01669096), healthy Bacillus Calmette-Gurin (BCG)-primed, HIV-negative adults were administered two doses (30-days apart) of M72/AS01. Blood samples were collected pre-dose 1, pre-dose 2 and 1, 7, 10, 14, 17 and 30 days post-dose 2. RNA expression in blood and peripheral-blood mononuclear cells (PBMCs) was quantified using microarray technology. The data analysis used as a reference, a PBMC-gene signature that was associated with the protective efficacy of a similarly adjuvanted candidate malaria vaccine. Peripheral-blood CD4+ T-cell reactivity, serum interferon-gamma (IFNG) concentrations and safety were also assessed. Twenty subjects completed the study and 18 subjects received two doses. The observed safety profile was similar to previous trials. Serum IFNG responses and M72-specific CD4+ T cell responses to vaccination were detected as expected, based on previous trial experience. PBMC and whole-blood RNA-expression data at day 14 post-dose 2 relative to pre-vaccination and whole-blood RNA-expression data at 7, 10, and 17 days post-dose 2 relative to pre-vaccination could be used to classify vaccine recipients into gene-signature positive or gene-signature negative groups. In conclusion, whole blood sampled from the 7, 10, 14, or 17 day post-vaccination time points, in addition to pre-vaccination, could be selected to assess potentially clinically relevant responses to M72/AS01 using transcriptome analysis.

164

van den Berg RA, De Mot L, Leroux-Roels G, Bechtold V, Clement F, Coccia M, Jongert E, Evans TG, Gillard P, van der Most RG