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Efficacy of recombinant BCG vaccine candidates against Mycobacterium bovis infection in goats
J Figl(1) H Köhler(1) N Wedlich(1) E Liebler-Tenorio(1) K von Pückler(2) S Mamerow(1,7) M Rissmann(1) R Ulrich(7) L Grode(3) G Parzmair(3) G Krishnamoorthy(4) N E Nieuwenhuizen(4) S HE Kaufmann(4,5,6) C Menge(1)
1:Friedrich-Loeffler-Institut, Institute of Molecular Pathogenesis, Jena; 2:Justus-Liebig-University Gießen, Small Animal Clinic – Radiology; 3:Vakzine Projekt Management GmbH; 4:Max Planck Institute for Infection Biology, Department of Immunology, Berlin; 5:Max Planck Institute for Multidisciplinary Sciences, Göttingen; 6:Hagler Institute for Advanced Study, Texas A&M University; 7:Friedrich-Loeffler-Institut, Department of Experimental Animal Facilities and Biorisk Management, Greifswald – Isle of Riems
To generate a tuberculosis (TB) vaccine candidate more potent than Bacillus Calmette-Guérin (BCG), a recombinant BCG strain VPM1002 (BCGΔureC::hly) was genetically engineered to express listeriolysin from Listeria monocytogenes. Derivatives VPM1002 Δpdx1 (PDX) and VPM1002 ΔnuoG (NUOG) were further modified to improve safety and efficacy, respectively. We aimed to comparatively assess the efficacy of the novel vaccine candidates in a Mycobacterium bovis intra-bronchial infection model in goats. Four groups of juvenile goats (n=8) were vaccinated subcutaneously with either BCG, VPM1002, its derivatives, or served as controls. Four months later, all animals were challenged intra-bronchially with 2x10³ CFU of M. bovis and were monitored until 5 months post infection. At necropsy, tissue samples were taken for bacterial culture, and lungs were fixed intra-thoracically and analyzed by computed tomography (CT). After challenge, none of the goats were clinically ill, but CT analysis revealed lung lesions in all goats of the control, VPM1002, PDX, and NUOG groups and in 6/8 BCG-vaccinated animals. The extent of the lesions varied, with high numbers in controls and PDX-vaccinated goats, reduced numbers in BCG-vaccinated goats and lowest numbers in the NUOG and VPM1002 group. M. bovis was re-isolated from the mediastinal and tracheobronchial lymph nodes. The proportion of culture positive animals in the groups corresponded with the average extent of lung lesions documented for the group. In conclusion, genetic modification of BCG has generated derivatives more effective (VPM1002 and NUOG) when applied to protect goats from the detrimental effects of bovine tuberculosis.