How do vaccines interact with human cells?

In a recently published study, scientists have identified various transcriptional programs induced in human antigen presenting cells (APCs) by various vaccines. The article published in October issue of Nature Communications sheds new light on the mechanisms of vaccine interaction with human dendritic cells (DCs), a primary APC involved in vaccination response.

Previous studies have shown that vaccination mostly depend on dendritic cells. DCs are highly efficient in presentation of antigen. In response to a pathogen, DCs transcribe various set of genes that then interact with each other. Although, many sub-populations of DCs have been identified in human blood, skin and other tissues, the role of these populations in eliciting specific immune response to different vaccines is not entirely known. Furthermore, it is not much known about the various transcriptional programs initiated in response to different vaccines.

Romain Banchereau and colleagues from Baylor Institute for Immunology Research, Dallas and Jackson Laboratory for Genomic Medicine, Farmington used a unique multi-step approach to understand how human DCs respond to vaccine challenge in vitro. They studied transcriptional changes in DCs that were first generated by culturing monocytes (a precursor to DC) with different cytokines and then exposing them to a number of pathogens. The researchers observed a broad spectrum of unique and common transcriptional responses to pathogens over time. To further understand the biological significance of these transcriptional responses, the scientists generated a framework that groups transcripts into modules based on their co-expression across pathogens, time points, and DCs. They found that modules represented alteration of many biological pathways including interferon response, inflammation, antigen processing and presentation, DC maturation and T cell activation.

The investigators then applied the same approach to study transcriptional responses of various APCs to 13 commercially available vaccines in vitro and observed that response to different vaccine was mediated through unique APC subsets. In a further effort to understand the differences in immune pathways required for vaccination to those that are responsible for pathogenesis of a particular disease, the scientists applied the same framework to analyze transcriptional profile of individuals vaccinated with influenza vaccine and individuals with asymptomatic and symptomatic influenza infections. They found that vaccinated individuals showed similar transcriptional profiles to asymptomatic individuals and both showed a mild signature. In contrast, symptomatic individuals showed strong response. The researchers acknowledge that this approach can help in identifying which pathways are require for vaccination and which for establishing infection and this distinction between two pathways can help in development of safer and more effective vaccines in future.

Overall, this study provides a good understanding of transcriptional response of DCs to current vaccines and will certainly add in development of next generation vaccines, in which specific sub-populations of APCs can be targeted for a more effective response to a particular pathogen.