Author/Authors :
Dalirfardouei, Razieh Research Center for Molecular Medicine - Hamadan University of Medical Sciences, Hamadan - Department of Medical Biotechnology - Faculty of Medicine - Mashhad University of Medical Sciences , Tafaghodi, Mohsen Nanotechnology Research Center - Institute of Pharmaceutical Technology - Mashhad University of Medical Sciences , Meshkat, Zahra Antimicrobial Resistance Research Center - Mashhad University of Medical Sciences, Mashhad , Najafi, Adel Laboratory Division - Fatemieh Hospital - Hamadan University of Medical Sciences , Gholoobi, Aida Medical Genetics Research Center - Mashhad University of Medical Sciences , Nabavinia, Maryam Sadat Department of Pharmacognosy - Faculty of Pharmacy and Pharmaceutical Sciences Research Center - Shahid Sadoughi University of Medical Sciences, Yazd , Sajedifar, Samineh Mashhad University of Medical Sciences , Meshkat, Mojtaba Mashhad Branch - Isalmic Azad University, Mashhad , Badiee, Ali Nanotechnology Research Center - Institute of Pharmaceutical Technology - Mashhad University of Medical Sciences , Ramezani, Mohammad Nanotechnology Research Center - Institute of Pharmaceutical Technology - Mashhad University of Medical Sciences , Varasteh, Abdol-Reza Immunobiochemistry Lab - Allergy Research Center - Mashhad University of Medical Sciences , Naderinasab, Mahboubeh Antimicrobial Resistance Research Center - Mashhad University of Medical Sciences, Mashhad
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 (lacticco-
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 :
CpG ODN , DNA vaccine , Mtb72F , Mycobacterium tuberculosis , PLGA nanoparticles , Tuberculosis vaccine
