ANTI TUBERCULOSIS CANDIDATE VACCINE TESTING IN RHESUS MONKEYS: MYCOBACTERIA

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Normal rhesus monkeys (RM) were challenged with a range of concentrations (1 X 102-6 X 106) of Mycobacterium tuberculosis (MTB), strain H37Rv, to determine optimal challenge dose. Groups of RM previously vaccinated and boosted with 2 doses of culture-filtrate protein (CFP) from H37Rv together with QS-21 adjuvant or QS-21 alone were then challenged with 6 X 106 H37Rv MTB and were followed clinically and immunologically. Over several months, all 12 RM showed evidence of tuberculosis clinically or/and at necropsy. Disease progression was more rapid in some and quite slow in other individuals, but no statistically significant association with the vaccinations could be discerned. There were only 4 RM/group, however, and only clear-cut differences could be expected to have shown significance. Longitudinal in vitro blastogenesis responses to Concanavalin A, phytohemagglutinin, tuberculin, CFP and to MTB 10 Kd protein post-challenge with live H37Rv failed to show any consistent statistically significant differences between the 3 groups. These results were consistent with our prior studies that showed no significant blastogenic differences or differences in skin test results using CFP or tuberculin in vaccinated vs unvaccinated groups post-vaccination or post-boosting. The data indicated that the QS-21 adjuvant was itself immunosuppressive; higher doses of CFP in QS-21 tended to overcome the suppression. The results show that QS-21 is not an acceptable adjuvant for use in primates, and leaves open the question as to the possible effectiveness of CFP as a protective vaccine in combination with an appropriate adjuvant. Titration studies are in progress to determine the relative lethality in RM between the H37Rv and the more pathogenic Erdman strain of MTB. At present, there does not