title: Vaccination with Toxoplasma lysate antigen and CpG oligodeoxynucleotides: comparison of immune responses in intranasal versus intramuscular administrations.
abstract: Toxoplasma gondii (T. gondii) is one of the most successful intracellular protozoan parasites on earth and highly prevalent in most warm-blooded vertebrates. There are no drugs that target the chronic cyst stage of this infection; therefore, development of an effective vaccine would be an important advance in disease control. Oligodeoxynucleotides (ODN) which contain immunostimulatory CG motifs (CpG ODN) can promote T-helper 1 (Th1) responses, an adjuvant activity that is desirable for vaccination against intracellular pathogen. In this study, we compare the immune responses of Toxoplasma susceptible C57BL/6 mice following intranasal and intramuscular vaccination with Toxoplasma lysate antigen (TLA) with or without CpG ODN as adjuvant. Immunized and control non-immunized mice were challenged with 85 cyst of the moderately virulent Beverley strain of T. gondii. Intranasal vaccination gave significantly a higher protection compared to other groups as indicated by prolonged survival and significantly reduced brain cyst burden (P < 0.01). Intranasal vaccination stimulated cellular immunity towards Th1 response characterized by significant INF-γ production (P < 0.01). Furthermore, fecal IgA antibody levels as an indicator of mucosal immune responses were significantly higher (P < 0.05) in intranasal vaccinated group before the challenge compared to all other groups. Intranasal vaccination was not able to upgrade the Th1 humoral arm. In contrast, intramuscular vaccination enhanced humoral immunity towards a type Th1 pattern characterized by a significant increase of specific IgG and Ig2a. Our results suggest that intranasal administration of CpG/TLA would provide a stable, pronounced, and effective vaccine against toxoplasmosis through stimulation of Th1 cellular immunity and mucosal IgA.
authors.affiliation: Department of Medical Parasitology, Faculty of Medicine, Umm AL-Qura University, Makkah, Kingdom of Saudi Arabia, malky197@hotmail.com.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: EL-Malky
authors.forename: Saeed A
authors.initials: SA
authors.lastname: Al-Harthi
authors.forename: Raafat T
authors.initials: RT
authors.lastname: Mohamed
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: EL Bali
authors.forename: Niveen S
authors.initials: NS
authors.lastname: Saudy
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D018928:Immunity, Mucosal; D007070:Immunoglobulin A; D007273:Injections, Intramuscular; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014122:Toxoplasma / Q000378:metabolism*; D014123:Toxoplasmosis / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; C408982:CPG-oligonucleotide; D007070:Immunoglobulin A; D009838:Oligodeoxyribonucleotides; D016052:Protozoan Vaccines
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