MTBVAC vaccine is safe, immunogenic and confers protective efficacy against Mycobacterium tuberculosis in newborn mice

Nacho Aguilo, Santiago Uranga, Dessislava Marinova, Marta Monzon, Juan Badiola, Carlos Martin, Nacho Aguilo, Santiago Uranga, Dessislava Marinova, Marta Monzon, Juan Badiola, Carlos Martin

Abstract

Development of novel more efficient preventive vaccines against tuberculosis (TB) is crucial to achieve TB eradication by 2050, one of the Millennium Development Goals (MDG) for the current century. MTBVAC is the first and only live attenuated vaccine based on a human isolate of Mycobacterium tuberculosis developed as BCG-replacement strategy in newborns that has entered first-in-human adult clinical trials. In this work, we characterize the safety, immunogenicity and protective efficacy of MTBVAC in a model of newborn C57/BL6 mice. Our data clearly indicate that MTBVAC is safe for newborn mice, and does not affect animal growth or organ development. In addition, MTBVAC-vaccinated mice at birth showed enhanced immunogenicity and better protection against M. tuberculosis challenge in comparison with BCG.

Keywords: MTBVAC; Neonates; Newborn mice; Tuberculosis vaccine.

Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1
Figure 1
Weight monitoring of C57/BL6 mice immunized at birth for safety evaluation. Groups of at least twelve newborn C57/BL6 mice were vaccinated at birth with MTBVAC, BCG or PBS. Four weeks post-birth, mice were divided by gender and weight was monitored weekly. Data showed in the figure correspond to mice weighed at four and seven weeks post-birth. A representative experiment of two is shown. Data in the graphs are represented as mean ± SEM. Statistical analysis was done using a one-way ANOVA test to compare different vaccination groups for each age and gender. No statistical differences were found.
Figure 2
Figure 2
Immunogenicity conferred by vaccination at birth in C57/BL6 mice. Groups of six newborn C57/BL6 mice were vaccinated with MTBVAC, BCG or PBS. Immunogenicity was studied at eight weeks post-birth. Animals were humanely sacrificed and a cellular suspension from spleen was obtained. Cells were stimulated with PPD (A) or Ag85B (B) for 48 h and subsequently IFNg analysed in cell supernatant by ELISA. A representative experiment of two is shown. Data in the graphs are represented as mean ± SEM. One-way ANOVA test with Bonferroni post analysis was performed to calculate statistical significance. *p 

Figure 3

Protective efficacy conferred by vaccination…

Figure 3

Protective efficacy conferred by vaccination at birth in C57/BL6 mice. Groups of three…

Figure 3
Protective efficacy conferred by vaccination at birth in C57/BL6 mice. Groups of three to nine newborn C57/BL6 mice were vaccinated with MTBVAC, BCG or PBS. At eight weeks post-birth, animals were challenged intranasally with H37Rv and four weeks later CFUs were determined in lungs (A) and spleen (B). Data of two independent experiments are shown in the figure. Data in the graphs are represented as mean ± SEM. One-way ANOVA test with Bonferroni post analysis was performed to calculate statistical significance. *p 
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References
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Figure 3
Figure 3
Protective efficacy conferred by vaccination at birth in C57/BL6 mice. Groups of three to nine newborn C57/BL6 mice were vaccinated with MTBVAC, BCG or PBS. At eight weeks post-birth, animals were challenged intranasally with H37Rv and four weeks later CFUs were determined in lungs (A) and spleen (B). Data of two independent experiments are shown in the figure. Data in the graphs are represented as mean ± SEM. One-way ANOVA test with Bonferroni post analysis was performed to calculate statistical significance. *p 

References

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