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Open Access Research article

Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response

Magali Matsumiya1*, Stephanie A Harris1, Iman Satti1, Lisa Stockdale1, Rachel Tanner1, Matthew K O’Shea1, Michelle Tameris2, Hassan Mahomed34, Mark Hatherill2, Thomas J Scriba2, Willem A Hanekom2, Helen McShane2 and Helen A Fletcher15*

Author Affiliations

1 Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford, UK

2 South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa

3 Division of Community Health, Stellenbosch University, Stellenbosch, South Africa

4 Metropolitan District Health Services, Western Cape, Government Health, Cape Town, South Africa

5 Current affiliation: London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK

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BMC Infectious Diseases 2014, 14:314  doi:10.1186/1471-2334-14-314

Published: 9 June 2014

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.

Trial registration

ClinicalTrials.gov number NCT00953927

Keywords:
Tuberculosis; Vaccine; Innate immunity; Transcriptomics; MVA85A