Evaluation of PLGA, lipid-PLGA hybrid nanoparticles, and cationic pH-sensitive liposomes as tuberculosis vaccine delivery systems in a Mycobacterium tuberculosis challenge mouse model - A comparison.
M M Szachniewicz, M A Neustrup, S J F van den Eeden, K E van Meijgaarden, Kees L M C Franken, S van Veen, R I Koning, R W A L Limpens, A Geluk, J A Bouwstra, T H M Ottenhoff
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引用次数: 0
Abstract
Tuberculosis (TB) continues to pose a global threat for millennia, currently affecting over 2 billion people and causing 10.6 million new cases and 1.3 million deaths annually. The only existing vaccine, Mycobacterium Bovis Bacillus Calmette-Guérin (BCG), provides highly variable and inadequate protection in adults and adolescents. This study explores newly developed subunit tuberculosis vaccines that use a multistage protein fusion antigen Ag85b-ESAT6-Rv2034 (AER). The protection efficacy, as well as in vivo induced immune responses, were compared for five vaccines: BCG; AER-CpG/MPLA mix; poly(D,L-lactic-co-glycolic acid) (PLGA); lipid-PLGA hybrid nanoparticles (NPs); and cationic pH-sensitive liposomes (the latter three delivering AER together with CpG and MPLA). All vaccines, except the AER-adjuvant mix, induced protection in Mycobacterium tuberculosis (Mtb)-challenged C57/Bl6 mice as indicated by a significant reduction in bacterial burden in lungs and spleens of the animals. Four AER-based vaccines significantly increased the number of circulating multifunctional CD4+ and CD8+ T-cells producing IL-2, IFNγ, and TNFα, exhibiting a central memory phenotype. Furthermore, AER-based vaccines induced an increase in CD69+ B-cell counts as well as high antigen-specific antibody titers. Unexpectedly, none of the observed immune responses were associated with the bacterial burden outcome, such that the mechanism responsible for the observed vaccine-induced protection of these vaccines remains unclear. These findings suggest the existence of non-classical protective mechanisms for Mtb infection, which could, once identified, provide interesting targets for novel vaccines.
期刊介绍:
The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.