Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | 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

Authors: Magali Matsumiya, Stephanie A Harris, Iman Satti, Lisa Stockdale, Rachel Tanner, Matthew K O’Shea, Michelle Tameris, Hassan Mahomed, Mark Hatherill, Thomas J Scriba, Willem A Hanekom, Helen McShane, Helen A Fletcher

Published in: BMC Infectious Diseases | Issue 1/2014

Login to get access

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
Appendix
Available only for authorised users
Literature
1.
2.
Colditz GA, Brewer TF, Berkey CS, Burdick E, Fineberg HV, Mosteller F: Efficacy of BCG vaccine in the prevention of tuberculosis. JAMA. 1994, 271: 698-702. 10.1001/jama.1994.03510330076038.CrossRefPubMed
3.
Ottenhoff THM, Kaufmann SHE: Vaccines against tuberculosis: where are we and where do we need to go?. PLoS Pathog. 2012, 8: e1002607-10.1371/journal.ppat.1002607.CrossRefPubMedPubMedCentral
4.
Tameris MD, Hatherill M, Landry BS, Scriba TJ, Snowden MA, Lockhart S, Shea JE, McClain JB, Hussey GD, Hanekom WA, Mahomed H, McShane H: Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet. 2013, 6736: 1-8.
5.
Hawkridge T, Scriba TJ, Gelderbloem S, Smit E, Tameris M, Moyo S, Lang T, Veldsman A, Hatherill M, Van Der Merwe L, Fletcher HA, Mahomed H, Hill AVS, Hanekom WA, Hussey GD, McShane H: Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa. J Infect Dis. 2008, 198: 544-552. 10.1086/590185.CrossRefPubMedPubMedCentral
6.
Sander CR, Pathan AA, Beveridge NER, Poulton I, Minassian A, Alder N, Van Wijgerden J, Hill AVS, Gleeson FV, Davies RJO, Pasvol G, McShane H: Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in Mycobacterium tuberculosis-infected individuals. Am J Respir Crit Care Med. 2009, 179: 724-733. 10.1164/rccm.200809-1486OC.CrossRefPubMedPubMedCentral
7.
Minassian AM, Rowland R, Beveridge NER, Poulton ID, Satti I, Harris S, Poyntz H, Hamill M, Griffiths K, Sander CR, Ambrozak DR, Price DA, Hill BJ, Casazza JP, Douek DC, Koup RA, Roederer M, Winston A, Ross J, Sherrard J, Rooney G, Williams N, Lawrie AM, Fletcher HA, Pathan AA, McShane H: A Phase I study evaluating the safety and immunogenicity of MVA85A, a candidate TB vaccine, in HIV-infected adults. BMJ Open. 2011, 1: e000223-CrossRefPubMedPubMedCentral
8.
Scriba TJ, Tameris M, Mansoor N, Smit E, van der Merwe L, Mauff K, Hughes EJ, Moyo S, Brittain N, Lawrie A, Mulenga H, de Kock M, Gelderbloem S, Veldsman A, Hatherill M, Geldenhuys H, Hill AVS, Hussey GD, Mahomed H, Hanekom WA, McShane H: Dose-finding study of the novel tuberculosis vaccine, MVA85A, in healthy BCG-vaccinated infants. J Infect Dis. 2011, 203: 1832-1843. 10.1093/infdis/jir195.CrossRefPubMed
9.
Scriba TJ, Tameris M, Mansoor N, Smit E, van der Merwe L, Isaacs F, Keyser A, Moyo S, Brittain N, Lawrie A, Gelderbloem S, Veldsman A, Hatherill M, Hawkridge A, Hill AVS, Hussey GD, Mahomed H, McShane H, Hanekom WA: Modified vaccinia Ankara-expressing Ag85A, a novel tuberculosis vaccine, is safe in adolescents and children, and induces polyfunctional CD4+ T cells. Eur J Immunol. 2010, 40: 279-290.CrossRefPubMedPubMedCentral
10.
Griffiths KL, Pathan AA, Minassian AM, Sander CR, Beveridge NER, Hill AVS, Fletcher HA, McShane H: Th1/Th17 cell induction and corresponding reduction in ATP consumption following vaccination with the novel Mycobacterium tuberculosis vaccine MVA85A. PLoS One. 2011, 6: e23463-10.1371/journal.pone.0023463.CrossRefPubMedPubMedCentral
11.
De Cassan SC, Pathan AA, Sander CR, Minassian A, Rowland R, Hill AVS, McShane H, Fletcher HA: Investigating the induction of vaccine-induced Th17 and regulatory T cells in healthy, Mycobacterium bovis BCG-immunized adults vaccinated with a new tuberculosis vaccine, MVA85A. Clin Vaccine Immunol. 2010, 17: 1066-1073. 10.1128/CVI.00047-10.CrossRefPubMedPubMedCentral
12.
Dye C, Fine PE: A major event for new tuberculosis vaccines. Lancet. 2013, 6736: 3-5.
13.
Querec TD, Akondy RS, Lee EK, Cao W, Nakaya HI, Teuwen D, Pirani A, Gernert K, Deng J, Marzolf B, Kennedy K, Wu H, Bennouna S, Oluoch H, Miller J, Vencio RZ, Mulligan M, Aderem A, Ahmed R, Pulendran B: Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol. 2009, 10: 116-125.CrossRefPubMed
14.
Gaucher D, Therrien R, Kettaf N, Angermann BR, Boucher G, Filali-Mouhim A, Moser JM, Mehta RS, Drake DR, Castro E, Akondy R, Rinfret A, Yassine-Diab B, Said EA, Chouikh Y, Cameron MJ, Clum R, Kelvin D, Somogyi R, Greller LD, Balderas RS, Wilkinson P, Pantaleo G, Tartaglia J, Haddad EK, Sékaly R-P: Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses. J Exp Med. 2008, 205: 3119-3131. 10.1084/jem.20082292.CrossRefPubMedPubMedCentral
15.
Nakaya HI, Wrammert J, Lee EK, Racioppi L, Marie-Kunze S, Haining WN, Means AR, Kasturi SP, Khan N, Li G-M, McCausland M, Kanchan V, Kokko KE, Li S, Elbein R, Mehta AK, Aderem A, Subbarao K, Ahmed R, Pulendran B: Systems biology of vaccination for seasonal influenza in humans. Nat Immunol. 2011, 12: 786-795. 10.1038/ni.2067.CrossRefPubMedPubMedCentral
16.
Furman D, Jojic V, Kidd B, Shen-Orr S, Price J, Jarrell J, Tse T, Huang H, Lund P, Maecker HT, Utz PJ, Dekker CL, Koller D, Davis MM: Apoptosis and other immune biomarkers predict influenza vaccine responsiveness. Mol Syst Biol. 2013, 9: 659-CrossRefPubMedPubMedCentral
17.
Ravindran R, Khan N, Nakaya HI, Li S, Loebbermann J, Maddur MS, Park Y, Jones DP, Chappert P, Davoust J, Weiss DS, Virgin HW, Ron D, Pulendran B: Vaccine activation of the nutrient sensor GCN2 in dendritic cells enhances antigen presentation. Science. 2013, 2 (December): 1-8.
18.
Pulendran B, Oh JZ, Nakaya HI, Ravindran R, Kazmin DA: Immunity to viruses: learning from successful human vaccines. Immunol Rev. 2013, 255: 243-255. 10.1111/imr.12099.CrossRefPubMedPubMedCentral
19.
20.
Antrobus RD, Lillie PJ, Berthoud TK, Spencer AJ, McLaren JE, Ladell K, Lambe T, Milicic A, Price DA, Hill AVS, Gilbert SC: A T Cell-Inducing Influenza Vaccine for the Elderly: Safety and Immunogenicity of MVA-NP + M1 in Adults Aged over 50 Years. PLoS One. 2012, 7: e48322-10.1371/journal.pone.0048322.CrossRefPubMedPubMedCentral
21.
McElhaney JE, Zhou X, Talbot HK, Soethout E, Bleackley RC, Granville DJ, Pawelec G: The unmet need in the elderly: how immunosenescence, CMV infection, co-morbidities and frailty are a challenge for the development of more effective influenza vaccines. Vaccine. 2012, 30: 2060-2067. 10.1016/j.vaccine.2012.01.015.CrossRefPubMedPubMedCentral
22.
Bodewes R, Fraaij PLA, Osterhaus ADME, Rimmelzwaan GF: Pediatric influenza vaccination: understanding the T-cell response. Expert Rev Vaccines. 2012, 11: 963-971. 10.1586/erv.12.69.CrossRefPubMed
23.
Meyer J, Harris SA, Satti I, Poulton ID, Poyntz HC, Tanner R, Rowland R, Griffiths KL, Fletcher HA, McShane H: Comparing the safety and immunogenicity of a candidate TB vaccine MVA85A administered by intramuscular and intradermal delivery. Vaccine. 2013, 31: 1026-1033. 10.1016/j.vaccine.2012.12.042.CrossRefPubMed
24.
Kauffmann A, Huber W: Microarray data quality control improves the detection of differentially expressed genes. Genomics. 2010, 95: 138-142. 10.1016/j.ygeno.2010.01.003.CrossRefPubMed
25.
Smyth GK: Limma: linear models for microarray data. Bioinforma Comput Biol Solut using R Bioconductor. Edited by: Gentleman R, Carey V, Dudoit S, Irizarry R, Huber W. 2005, New York: Springer, 397-420.CrossRef
26.
Shi W, Oshlack A, Smyth GK: Optimizing the noise versus bias trade-off for Illumina whole genome expression BeadChips. Nucleic Acids Res. 2010, 38: e204-10.1093/nar/gkq871.CrossRefPubMedPubMedCentral
27.
Ritchie ME, Diyagama D, Neilson J, van Laar R, Dobrovic A, Holloway A, Smyth GK: Empirical array quality weights in the analysis of microarray data. BMC Bioinformatics. 2006, 7: 261-10.1186/1471-2105-7-261.CrossRefPubMedPubMedCentral
28.
Tusher VG, Tibshirani R, Chu G: Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A. 2001, 98: 5116-5121. 10.1073/pnas.091062498.CrossRefPubMedPubMedCentral
29.
Zhang S: A comprehensive evaluation of SAM, the SAM R-package and a simple modification to improve its performance. BMC Bioinformatics. 2007, 8: 230-10.1186/1471-2105-8-230.CrossRefPubMedPubMedCentral
30.
Shen-Orr SS, Tibshirani R, Khatri P, Bodian DL, Staedtler F, Perry NM, Hastie T, Sarwal MM, Davis MM, Butte AJ: Cell type-specific gene expression differences in complex tissues. Nat Methods. 2010, 7: 287-289. 10.1038/nmeth.1439.CrossRefPubMedPubMedCentral
31.
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP: Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005, 102: 15545-15550. 10.1073/pnas.0506580102.CrossRefPubMedPubMedCentral
32.
Mootha VK, Lindgren CM, Eriksson K-F, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstråle M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP, Golub TR, Tamayo P, Spiegelman B, Lander ES, Hirschhorn JN, Altshuler D, Groop LC: PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003, 34: 267-273. 10.1038/ng1180.CrossRefPubMed
33.
Li S, Rouphael N, Duraisingham S, Romero-Steiner S, Presnell S, Davis C, Schmidt DS, Johnson SE, Milton A, Rajam G, Kasturi S, Carlone GM, Quinn C, Chaussabel D, Palucka AK, Mulligan MJ, Ahmed R, Stephens DS, Nakaya HI, Pulendran B: Molecular signatures of antibody responses derived from a systems biology study of five human vaccines. Nat Immunol. 2013, 15: 1-12.CrossRef
34.
Quintin J, Saeed S, Martens JHA, Giamarellos-Bourboulis EJ, Ifrim DC, Logie C, Jacobs L, Jansen T, Kullberg B-J, Wijmenga C, Joosten LAB, Xavier RJ, van der Meer JWM, Stunnenberg HG, Netea MG: Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe. 2012, 12: 223-232. 10.1016/j.chom.2012.06.006.CrossRefPubMed
35.
Zang S, Guo R, Zhang L, Lu Y: Integration of statistical inference methods and a novel control measure to improve sensitivity and specificity of data analysis in expression profiling studies. J Biomed Inform. 2007, 40: 552-560. 10.1016/j.jbi.2007.01.002.CrossRefPubMed
36.
McShane H, Pathan AA, Sander CR, Keating SM, Gilbert SC, Huygen K, Fletcher HA, Hill AV: Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat Med. 2004, 10: 1240-1244. 10.1038/nm1128.CrossRefPubMed
37.
Naranbhai V, Hill AVS, Abdool Karim SS, Naidoo K, Abdool Karim Q, Warimwe GM, McShane H, Fletcher H: Ratio of monocytes to lymphocytes in peripheral blood identifies adults at risk of incident tuberculosis among HIV-infected adults initiating antiretroviral therapy. J Infect Dis. 2013, 209: 1-10.
38.
Warimwe GM, Murungi LM, Kamuyu G, Nyangweso GM, Wambua J, Naranbhai V, Fletcher HA, Hill AVS, Bejon P, Osier FHA, Marsh K: The ratio of monocytes to lymphocytes in peripheral blood correlates with increased susceptibility to clinical malaria in Kenyan children. PLoS One. 2013, 8: e57320-10.1371/journal.pone.0057320.CrossRefPubMedPubMedCentral
39.
Merekoulias G, Alexopoulos EC, Belezos T, Panagiotopoulou E: Lymphocyte to monocyte ratio as a screening tool for influenza. Plos Curr. 2010, 2: RRN1154-CrossRefPubMedPubMedCentral
40.
Warimwe GM, Fletcher HA, Olotu A, Agnandji ST, Hill AVS, Marsh K, Bejon P: Peripheral blood monocyte-to-lymphocyte ratio at study enrollment predicts efficacy of the RTS,S malaria vaccine: analysis of pooled phase II clinical trial data. BMC Med. 2013, 11: 184-10.1186/1741-7015-11-184.CrossRefPubMedPubMedCentral
41.
Berthoud TK, Fletcher H, Porter D, Thompson F, Hill AVS, Todryk SM: Comparing human T cell and NK cell responses in viral-based malaria vaccine trials. Vaccine. 2009, 28: 21-27. 10.1016/j.vaccine.2009.09.132.CrossRefPubMed
42.
Matsumiya M, Stylianou E, Griffiths K, Lang Z, Meyer J, Harris SA, Rowland R, Minassian AM, Pathan AA, Fletcher H, Mcshane H: Roles for treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A. PLoS One. 2013, 8: 1-14.CrossRef
43.
Holmgaard RB, Zamarin D, Munn DH, Wolchok JD, Allison JP: Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med. 2013, 210: 1389-1402. 10.1084/jem.20130066.CrossRefPubMedPubMedCentral
Metadata
Title
Inflammatory and myeloid-associated gene expression before and one day after infant vaccination with MVA85A correlates with induction of a T cell response
Authors
Magali Matsumiya
Stephanie A Harris
Iman Satti
Lisa Stockdale
Rachel Tanner
Matthew K O’Shea
Michelle Tameris
Hassan Mahomed
Mark Hatherill
Thomas J Scriba
Willem A Hanekom
Helen McShane
Helen A Fletcher
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-314

Other articles of this Issue 1/2014

BMC Infectious Diseases 1/2014 Go to the issue

Research article

Incidence, pathogens and resistance patterns of nosocomial infections at a rural hospital in Gabon

Research article

A peptide fragment from the human COX3 protein disrupts association of Mycobacterium tuberculosisvirulence proteins ESAT-6 and CFP10, inhibits mycobacterial growth and mounts protective immune response

Research article

Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China

Research article

Antibiotic susceptibility of Clostridium difficile is similar worldwide over two decades despite widespread use of broad-spectrum antibiotics: an analysis done at the University Hospital of Zurich

Research article

TGF beta and IL13 in schistosomiasis mansoni associated pulmonary arterial hypertension; a descriptive study with comparative groups

Research article

Quantifying the clinical virulence of Klebsiella pneumoniae producing carbapenemase Klebsiella pneumoniae with a Galleria mellonellamodel and a pilot study to translate to patient outcomes
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits