Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response
Date
2014-06
Journal Title
Journal ISSN
Volume Title
Publisher
BioMed Central
Abstract
Background: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a
successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in
BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen,
cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this
population.
Methods: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination
with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the
adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early
gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis
of microarrays (SAM) statistical package and gene set enrichment analysis.
Results: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples.
Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher
IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation
in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely
correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in
how T cell responses develop in these two populations following vaccination with MVA85A.
Conclusion: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of
an adaptive immune response in South African infants but induction of regulatory pathways may be more important
in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an
important aspect of developing successful vaccines and vaccination strategies.
Description
CITATION: Matsumiya, M. et al. 2014. Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response. BMC Infectious Diseases, 14:314, doi:10.1186/1471-2334-14-314.
The original publication is available at http://bmcinfectdis.biomedcentral.com
The original publication is available at http://bmcinfectdis.biomedcentral.com
Keywords
Tuberculosis -- Vaccination -- South Africa, Immunization of children -- South Africa, Natural immunity -- South Africa, Immune response, MVA85A
Citation
Matsumiya, M. et al. 2014. Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response. BMC Infectious Diseases, 14:314, doi:10.1186/1471-2334-14-314.