Evaluation of the Mtb72F polyprotein vaccine in a rabbit model of tuberculous meningitis.
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.
Laboratory of Mycobacterial Immunity and Pathogenesis, The Public Health Research Institute, 225 Warren Street, Newark, NJ 07103, USA.
Liana
L
Tsenova
Ryhor
R
Harbacheuski
Andre L
AL
Moreira
Evette
E
Ellison
Wilfried
W
Dalemans
Mark R
MR
Alderson
Barun
B
Mathema
Steven G
SG
Reed
Yasir A W
YA
Skeiky
Gilla
G
Kaplan
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D001835:Body Weight / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D007110:Immunity, Active; D007117:Immunization, Secondary; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D012503:Saponins / Q000008:administration & dosage / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014390:Tuberculosis, Meningeal / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*
C501939:ASO2A adjuvant; D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D004338:Drug Combinations; D008050:Lipid A; D011994:Recombinant Proteins; D012503:Saponins; D032581:Tuberculosis Vaccines