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Evaluation of the Mtb72F Polyprotein Vaccine in a Rabbit Model of Tuberculous Meningitis

Liana Tsenova,¹ Ryhor Harbacheuski,¹ Andre L. Moreira,³ Evette Ellison,¹ Wilfried Dalemans,⁴ Mark R. Alderson,⁵ Barun Mathema,^2,7 Steven G. Reed,⁶ Yasir A. W. Skeiky,^5, and Gilla Kaplan^1*

Laboratory of Mycobacterial Immunity and Pathogenesis,¹ Tuberculosis Center, PHRI, Newark, New Jersey 07103,² Memorial Sloan Kettering Cancer Center, New York, New York 10021,³ GlaxoSmithKline Biologicals, Rixensart, Belgium,⁴ Corixa Corporation, Seattle, Washington 98104,⁵ Infectious Disease Research Institute, Seattle, Washington 98104,⁶ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York 10032⁷

Received 12 September 2005/ Returned for modification 9 November 2005/ Accepted 26 January 2006

Using a rabbit model of tuberculous meningitis, we evaluated the protective efficacy of vaccination with the recombinant polyprotein Mtb72F, which is formulated in two alternative adjuvants, AS02A and AS01B, and compared this to vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) alone or as a BCG prime/Mtb72F-boost regimen. Vaccination with Mtb72F formulated in AS02A (Mtb72F+AS02A) or Mtb72F formulated in AS01B (Mtb72F+AS01B) was protective against central nervous system (CNS) challenge with Mycobacterium tuberculosis H37Rv to an extent comparable to that of vaccination with BCG. Similar accelerated clearances of bacilli from the cerebrospinal fluid, reduced leukocytosis, and less pathology of the brain and lungs were noted. Weight loss of infected rabbits was less extensive for Mtb72F+AS02A-vaccinated rabbits. In addition, protection against M. tuberculosis H37Rv CNS infection afforded by BCG/Mtb72F in a prime-boost strategy was similar to that by BCG alone. Interestingly, Mtb72F+AS01B induced better protection against leukocytosis and weight loss, suggesting that the polyprotein in this adjuvant may boost immunity without exacerbating inflammation in previously BCG-vaccinated individuals.

Editor: J. L. Flynn

Present address: Aeras Global TB Vaccine Foundation, Bethesda, MD 20814.

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