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.

Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations

“…Evidently, CpG-ODN-adjuvanted recombinant hepatitis B virus vaccine has recently been approved for clinical use [ 32 ]. Thus far, several studies have reported the protective efficacies of protein and DNA vaccines formulated with CpG-ODN adjuvants [ 33 , 34 , 35 , 36 ]. In our current study, we found that the efficacy of the CpG-ODN-adjuvanted T. gondii VLP vaccine was significantly enhanced compared with unadjuvanted VLPs after one, two, and three immunizations.…”

Evaluation of the immune response in BALB/c mice induced by a novel DNA vaccine expressing GRA14 against Toxoplasma gondii

“…Selection of an adjuvant or a delivery system is as important as the selection of a vaccine candidate due to their significant function in increasing the immunogenicity of antigens, via induction of proper immune responses, improvement of the vaccines efficacy and determination of the type of immune responses. 33,40,41 It is more important that the immune responses are presented with right location and amount of antigens. Generally, antigens uptake in macrophages by phagocytosis or endocytosis processes can induce their activation.…”

Induction of mucosal immunity through systemic immunization: Phantom or reality?

“…vaccination can promote both systemic and mucosal immune responses, and protect against mucosal pathogen challenge. [30][31][32][33][34] For example, i.m. immunization with anti-caries DNA vaccine encoding S. mutans antigens fused to cytotoxic T lymphocyte antigen-4 (CTLA-4) elicited strong serum IgG and salivary IgA responses in both rabbits and monkeys.…”