Transcriptional profiling of vaccine-induced immune responses in humans and non-human primates

Abstract

There is an urgent need for pre-clinical and clinical biomarkers predictive of vaccine immunogenicity, efficacy and safety to reduce the risks and costs associated with vaccine development. Results emerging from immunoprofiling studies in non-human primates and humans demonstrate clearly that (i) type and duration of immune memory are largely determined by the magnitude and complexity of the innate immune signals and (ii) genetic signatures highly predictive of B-cell and T-cell responses can be identified for specific vaccines. For vaccines with similar composition, e.g. live attenuated viral vaccines, these signatures share common patterns. Signatures predictive of vaccine efficacy have been identified in a few experimental challenge studies. This review aims to give an overview of the current literature on immunoprofiling studies in humans and also presents some of our own data on profiling of licensed and experimental vaccines in non-human primates.

Figure 1

Overall blood gene signatures in non‐human primate immunized with seven marketed or experimental vaccines. Genome‐wise gene expression data were collected from 8 time points including 0 h (baseline), 4 h, 8 h, 24 h, 1 week, 2 weeks, 3 weeks and 4 weeks post vaccination. For each vaccine formulation, a one‐way anova was performed to select for signature genes modulated at any one of 7 time points post vaccination in comparison to the baseline at P ≤ 0.001. The heatmap shows expression values in Log(Ratio) of 23 653 sequences derived from the union of 10 anova gene lists. The signatures are robust and both common and unique signature clusters can be identified among tested vaccines. For examples, genes in clusters 6, 10 and 11 are generally upregulated in all tested vaccines at day 1 (i.e. 4, 8 and 24 h post vaccination) although the intensities are variable among vaccines; genes in clusters 9 and 14 are upregulated at later time points (weeks 2–4) whereas genes in clusters 2 and 13 are generally downregulated. There are also vaccine‐specific gene signatures such as cluster 4, which is specifically upregulated by Menactra and cluster 1, which is predominantly upregulated by MRKAd5 and Havrix.