Table 2 Strategies to increase efficacies of tuberculosis DNA vaccines

A. Use of vaccine cocktails:
Antigena Model Challengea Commentsb Ref.
ESAT-6, MPT64, Ag85B Mouse  MT/airIndividual vaccines: 0.25-0.41; cocktail: 0.63 [40]
ESAT-6, MPT63, MPT64, KatGMouse MT/airIndividual vaccines: 0.40-0.60; cocktail: 0.82[22]
Ag85B, MPT64, GM-CSFMouse MT/airIncreased in vitro proliferation and IFN-γ, but no improved protection [56]
B. Modifications:
AntigenModificationsModelChallengeCommentsRef.
ESAT-6, MPT64, KatG tPa signal peptideMouseMT/airBetter protection when signal peptide had been added e.g., tPa-ESAT-6: 0.72; ESAT-6: 0.41 [23]
Ag85BtPa signal peptideMouseMT/ivInfection contained longer when signal peptide added [28]
ESAT-6, MPT64Ubiquitin fusionsMouse MT/airBetter protection depending on ubiquitin-construct used e.g., Ubiqitin-MPT64: 0.52; MPT64: 0.35[57]
C. Prime-boost strategies:
Prime (DNA) BoostModelChallengeCommentRef.
Ag85AAg85A protein Adjuvant: MPLMouse MT/iv Better than DNA or protein alone, not as good as BCG (DNA: 0.28; DNA/protein: 0.46) [58]
Ag85AAg85A protein Adjuvant: SBAAS2AMouseMT/iv better than DNA or protein alone, as good as BCG (DNA: 0.53, DNA/protein: 1.03)[58]
HSP65 (ML)HSP65 (MT) protein Adjuvant: IFACattleNTimproved and more homogenous proliferative and IFN-γ responsesc  
ESAT-6/MPT63MVA-ESAT-6/MPT63MouseMT/ipIncrease in IFN-γ responses, primeboost as good as BCG fusion DNA/MVA ca. 0.90 to 2.70 [59]
Ag85BBCGMouseMT/airDNA/BCG: 1.67. Partially mediated by CD8 T-cells[60]
HSP65 (ML), HSP70, ApaBCGCattleMB/it Better protection than with BCG alone.(Mean pathology scores: Control or DNA: ca. 7; BCG: 3.2; DNA/BCG: 1.5)d  

aSee Table 1 legend.

b If not listed otherwise, results are given as relative lung protection value compared to BCG (see Table 1 legend).

cVordermeier and Hewinson, unpublished data.

dVordermeier, Hewinson and Buddle, unpublished data.

From: DNA Vaccines against Bacterial Pathogens

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