Molecular Signatures of Immunity and Immunogenicity in Infection and Vaccination

Abstract

Vaccinology aims to understand what factors drive vaccine-induced immunity and protection. For many vaccines, however, the mechanisms underlying immunity and protection remain incompletely characterized at best, and except for neutralizing antibodies induced by viral vaccines, few correlates of protection exist. Recent omics and systems biology big data platforms have yielded valuable insights in these areas, particularly for viral vaccines, but in the case of more complex vaccines against bacterial infectious diseases, understanding is fragmented and limited. To fill this gap, the EC supported ADITEC project (http://www.aditecproject.eu/; http://stm.sciencemag.org/content/4/128/128cm4.full) featured a work package on "Molecular signatures of immunity and immunogenicity," aimed to identify key molecular mechanisms of innate and adaptive immunity during effector and memory stages of immune responses following vaccination. Specifically, technologies were developed to assess the human immune response to vaccination and infection at the level of the transcriptomic and proteomic response, T-cell and B-cell memory formation, cellular trafficking, and key molecular pathways of innate immunity, with emphasis on underlying mechanisms of protective immunity. This work intersected with other efforts in the ADITEC project. This review summarizes the main achievements of the work package.

Keywords: assays; biomarkers; immunity; immunity and infections; vaccines.

Figure 1

Gene set enrichment results generated with the tmod R package. (A) Enrichment in gene modules in each individual at 26 weeks postvaccination compared with baseline. (B) Gene set enrichment in both groups and between the groups at different time points compared with baseline. Red and blue indicate the proportion of genes in a particular module that is upregulated or downregulated respectively. Width of each box relates to its effect size, while brighter colors indicate lower p-values. Panel (B) represents a selection of a larger number of enriched gene modules.

Figure 2

Identification of human CD4+ memory T-cell subsets based on the differential expression of chemokine receptors.

Figure 3

Pentraxin 3 (PTX3) as endogenous adjuvant. PTX3 is locally produced at sites of infection or inflammation by myeloid cells in response to primary pro-inflammatory cytokines and toll-like receptor (TLR) engagement. In addition, the PTX3 gene is rapidly upregulated after treatment with selected adjuvants (MF59; CpG). PTX3 plays essential roles in the immune response to recognized pathogens: it is an active player in the innate immune response to microbes, acting as an opsonin and enhancing phagocytosis. Moreover, PTX3 is involved in immunoglobulin production and class switching from IgM to IgG, promoting humoral adaptive responses. The function of PTX3 as a bridge between the humoral arms of the innate and adaptive immune systems is in agreement with a role as endogenous adjuvant.