The TB research program evolves around the preclinical evaluation of improved vaccine regimes by investigating aspects of vaccine safety, immunogenicity, adjuvanticity and protective efficacy in the NHP. Implemented and validated measures include pathology, radiography, bacteriology and clinical surrogates (hematology, clinical chemistry and metabolomics) for standardised readout of NHP TB, systemic inflammation and vaccine-mediated protection as well as for refinement of animal testing. The research focuses on the identification of biomarkers and mechanisms of inflammation, pathogenesis and protection. Multiplex (Luminex) assay and flow cytometry (LSR-II®, FACSaria®) protocols are established for in-depth analysis of innate and adaptive cellular immunity. Besides macaques (M. mulatta, M. fascicularis) we have piloted TB in common marmosets (Callithrix jacchus) as a smaller species that can be used for TB drug studies and advanced bio-imaging. The BPRC joined the Collaboration for TB Vaccine Development (CTVD, at the initiative of the Bill & Melinda Gates Foundation) as a NHP Central Service Facility and currently is implementing advanced PET-CT imaging for refined readout of NHP TB.
MVA.85A boosting of BCG and an attenuated, phoP deficient M. tuberculosis vaccine both show protective efficacy against tuberculosis in rhesus macaques.
Verreck FA, Vervenne RA, Kondova I, van Kralingen KW, Remarque EJ, Braskamp G, van der Werff NM, Kersbergen A, Ottenhoff TH, Heidt PJ, Gilbert SC, Gicquel B, Hill AV, Martin C, McShane H, Thomas AW.
PLoS One. 2009;4(4):e5264. doi: 10.1371/journal.pone.0005264. Epub 2009 Apr 15. Erratum in: PLoS One. 2011;6(2). doi:10.1371/annotation/e599dafd-8208-4655-a792-21cb125f7f66.
Creativity in tuberculosis research and discovery.
Younga D, Verreck FA.
Tuberculosis (Edinb). 2012 Mar;92 Suppl 1:S14-6. doi: 10.1016/S1472-9792(12)70006-9. Review.
Tuberculosis is associated with expansion
of a motile, permissive and immunomodulatory CD16+
monocyte population via the IL-10/STAT3 axis.
Lastrucci C, Bénard A, Balboa L, Pingris K, Souriant S, Poincloux R, Al Saati T, Rasolofo V, González-Montaner P, Inwentarz S, Moranã E, Kondova I, Verreck FAW, Sasiain M, Neyrolles O, Maridonneau-Parini I, Lugo-Villarino G, and Cougoule C. (accepted for publication in Cell Research, 2015).