Different Innate Signatures Induced in Human Monocyte-derived Dendritic Cells by Wild-Type Dengue 3 Virus, Attenuated but Reactogenic Dengue 3 Vaccine Virus, or Attenuated Nonreactogenic Dengue 1-4 Vaccine Virus Strains

Abstract

DNA microarrays were used to assess the innate gene signature in human myeloid dendritic cells infected with chimeric dengue 1-4 vaccines, a wild-type dengue 3 virus, or a classically attenuated serotype 3 vaccine shown to be reactogenic in humans. We observed a very reproducible signature for each of the 4 chimeric dengue vaccines, involving stimulation of type I interferon and associated genes, together with genes encoding chemokines and other mediators involved in the initiation of adaptive responses. In contrast, wild-typeDEN3 virus induced a predominantly inflammatory profile, while the reactogenic attenuated serotype 3 vaccine appeared to induce a blunted response.

Dengue Virus Type 3 Isolated from a Fatal Case with Visceral Complications Induces Enhanced Proinflammatory Responses and Apoptosis of Human Dendritic Cells

“…The data presented here could be of help to enhance understanding of the severe or fatal outcomes observed in several dengue patients, as previously suggested (2). Finally, in view of our data and taking into account previous results by Palmer et al (34) in studies of the deficient activation of T cells by DCs infected with DENV, the high infection and apoptosis levels observed in DENV3/5532-infected mdDCs could impair DENV3 antigen presentation to T lymphocytes, affecting adaptive immune responses.…”

Strategic Applications of Gene Expression: From Drug Discovery/Development to Bedside

“…In general, the gene expression results were consistent with the degree of toxic effects observed in more traditional assays, such as the abnormal toxicity test and the leukopenic toxicity test (72)(73)(74). More recently, the systems vaccinology approach describes using the genome-wide gene expression underlying the host responses to vaccination (75)(76)(77)(78). In these studies, blood signature genes associated with B cell or T cell response were flagged as potential biomarkers to help differentiate vaccine efficacy or immunogenicity.…”

Immunosignatures can predict vaccine efficacy

“…However, gene expression profiles indirectly measure the antibody response, not the specificity of antibody reactivity. In the case of attenuated dengue fever vaccines, gene expression profiles were identical for different serotypes (21) and are not descriptive of the adverse response of vaccination with the wrong serotypes of virus (22,23). Immunosignatures should provide a valuable addition to systems vaccinology, and at times may alone be sufficient for evaluation.…”