A novel formulation of Mtb72F DNA vaccine for immunization against tuberculosis

Document Type : Original Article

Authors

1 Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

2 Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Nanotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran

4 Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

5 Laboratory Division, Fatemieh Hospital, Hamadan University of Medical Sciences, Hamadan, Iran

6 Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

7 Department of Pharmacognosy, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

8 Mashhad University of Medical Sciences, Mashhad, Iran

9 Mashhad Branch, Isalmic Azad University, Mashhad, Iran

10 Immunobiochemistry Lab, Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): 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.

Keywords


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