A novel formulation of Mtb72F DNA vaccine for immunization against tuberculosis.

Abstract:

Objectives:Mycobacterium tuberculosis (M. tuberculosis), an intracellular pathogen, causes 1.5 million deaths globally. Bacilli Calmette-Guérin (BCG) is commonly administered to protect people against M. tuberculosis infection; however, there are some obstacles with this first-generation vaccine. DNA vaccines, the third generation vaccines, can induce cellular immune responses for tuberculosis (TB) protection. In this study, optimized DNA vaccine (pcDNA3.1-Mtb72F) entrapped in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was used to achieve higher immunogenicity. Materials and Methods:Plasmid Mtb72F was formulated in PLGA NPs using double emulsion method in the presence of TB10.4 and/or CpG as an adjuvant. Female BALB/c mice were immunized either with NP-encapsulated Mtb72F or naked Mtb72F with or without each adjuvant, using the BCG-prime DNA boost regimen. Results:These NPs were approximately 250 nm in diameter and the nucleic acid and protein encapsulation efficiency were 80% and 25%, respectively. The NPs smaller than 200 nm are able to promote cellular rather than humoral responses. The immunization with the formulation consisting of Mtb72F DNA vaccine and TB10.4 entrapped in PLGA NPs showed significant immunogenicity and induced predominantly interferon-ɣ (IFN-ɣ) production and higher INF-ɣ/interleukin-4 (IL-4) ratio in the cultured spleen cells supernatant. Conclusion:PLGA NPs loaded with Mtb72F DNA-based vaccine with TB10.4 could be considered as a promising candidate for vaccination against TB. These results represent an excellent initial step toward development of novel vaccine for TB protection.

journal_name

Iran J Basic Med Sci

authors

Dalirfardouei R,Tafaghodi M,Meshkat Z,Najafi A,Gholoobi A,Nabavinia MS,Sajedifar S,Meshkat M,Badiee A,Ramezani M,Varasteh AR,Naderinasab M

doi

10.22038/ijbms.2020.41806.9881

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

826-832

issue

6

eissn

2008-3866

issn

2008-3874

journal_volume

23

pub_type

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