Synergistic effect of rSAG1 and rGRA2 antigens formulated in PLGA microspheres in eliciting immune protection against Toxoplasama gondii.
There is still no human vaccine against Toxoplasma gondii (T. gondii), as one of the most successful parasites. In present study, we designed a subunit vaccine composed of recombinant SAG1 (rSAG1) and recombinant GRA2 (rGRA2) proteins. In order to improve the induced immune responses, rSAG1 and rGRA2 were adsorbed on Poly (DL-lactide-co-glycolide) (PLGA) microspheres (MS) prepared by double emulsion solvent evaporation method. BALB/c mice were subcutaneously vaccinated by rSAG1-adsorbed PLGA MS (rSAG1-PLGA), rGRA2-adsorbed PLGA MS (rGRA2-PLGA), and the mixture of both formulations (rSAG1/rGRA2-PLGA), twice with a 3-week interval. PLGA MS characteristics, protein release, cellular and humoral immune responses, and protection against acute toxoplasmosis were evaluated. All vaccinated mice induced significantly partial protection and longer survival times associated with higher IFN-γ/IL-10 ratio and higher amount of Toxoplasma-specific IgG antibodies compared to control groups. Interestingly, the synergistic effect of rSAG1 and rGRA2 in eliciting more potent cellular and humoral responses and consequently higher protection in comparison to single antigen was confirmed. This study introduces the mixture of rSAG1 and rGRA2 (derived from different stages of Toxoplasma life-cycle) formulated in PLGA MS as a promising candidate in vaccine development against T. gondii.
Molecular Parasitology Laboratory, Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran; Recombinant Protein Production Department, Research and Production Complex, Pasteur Institute of Iran, Karaj, Iran.
Mojgan
M
Allahyari
Molecular Parasitology Laboratory, Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran.
Reyhaneh
R
Mohabati
Molecular Parasitology Laboratory, Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran.
Samira
S
Amiri
Molecular Parasitology Laboratory, Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran.
Ahmad Reza
AR
Esmaeili Rastaghi
Molecular Parasitology Laboratory, Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran.
Jalal
J
Babaie
Department of Immunology, Pasteur Institute of Iran, Tehran, Iran.
Mehdi
M
Mahdavi
Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: vatanara@sina.tums.ac.ir.
Alireza
A
Vatanara
Molecular Parasitology Laboratory, Department of Parasitology, Pasteur Institute of Iran, Tehran, Iran. Electronic address: majid.golkar@gmail.com.
Majid
M
Golkar
D000327:Adsorption; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D004337:Drug Carriers; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011247:Pregnancy; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000517:prevention & control; D022223:Vaccines, Subunit / Q000276:immunology
D000953:Antigens, Protozoan; D004337:Drug Carriers; C106990:Gra2 protein, Toxoplasma gondii; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; C047168:SAG1 antigen, Toxoplasma; D022223:Vaccines, Subunit; D016753:Interleukin-10; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007371:Interferon-gamma
Adsorption; PLGA microspheres; Toxoplasama gondii; Vaccine; rGRA2; rSAG1