MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies

Andrew D. White*, Laura Sibley, Charlotte Sarfas, Alexandra Morrison, Jennie Gullick, Simon Clark, Fergus Gleeson, Anthony McIntyre, Cecilia Lindestam Arlehamn, Alessandro Sette, Francisco Javier Salguero Bodes, Emma Rayner, Esteban Rodriguez, Eugenia Puentes, Dominick Laddy, Ann Williams, Mike Dennis, Carlos Martin, Sally Sharpe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

A single intradermal vaccination with MTBVAC given to adult rhesus macaques was well tolerated and conferred a significant improvement in outcome following aerosol exposure to M. tuberculosis compared to that provided by a single BCG vaccination. Vaccination with MTBVAC resulted in a significant reduction in M. tuberculosis infection-induced disease pathology measured using in vivo medical imaging, in gross pathology lesion counts and pathology scores recorded at necropsy, the frequency and severity of pulmonary granulomas and the frequency of recovery of viable M. tuberculosis from extrapulmonary tissues following challenge. The immune profiles induced following immunisation with MTBVAC reflect those identified in human clinical trials of MTBVAC. Evaluation of MTBVAC- and TB peptide-pool-specific T-cell cytokine production revealed a predominantly Th1 response from poly- (IFN-γ+TNF-α+IL2+) and multi-(IFN-γ+TNF-α+) functional CD4 T cells, while only low levels of Th22, Th17 and cytokine-producing CD8 T-cell populations were detected together with low-level, but significant, increases in CFP10-specific IFN-γ secreting cells. In this report, we describe concordance between immune profiles measured in clinical trials and a macaque pre-clinical study demonstrating significantly improved outcome after M. tuberculosis challenge as evidence to support the continued development of MTBVAC as an effective prophylactic vaccine for TB vaccination campaigns.

Original languageEnglish
Article number4
Number of pages10
Journalnpj Vaccines
Volume6
Issue number1
Early online date4 Jan 2021
DOIs
Publication statusE-pub ahead of print - 4 Jan 2021

Bibliographical note

Funding Information:
This work was supported by the Department of Health, UK and a grant from Aeras. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. We thank the staff of the Biological Investigations Group at PHE Porton and the PHE macaque colonies for assistance in conducting studies, Laura Hunter for histology support, Faye Lanni and Neil McCloud for bacteriology and aerobiology support, Helen Mearns from SATVI for advice aligning macaque immunological methods with protocols applied in MTBVAC clinical trials.

Fingerprint

Dive into the research topics of 'MTBVAC vaccination protects rhesus macaques against aerosol challenge with M. tuberculosis and induces immune signatures analogous to those observed in clinical studies'. Together they form a unique fingerprint.

Cite this