Abstract
BackgroundA widely prevalent disease, toxoplasmosis poses serious health threats to both humans and animals; therefore, development of an ideal DNA vaccine against Toxoplasma gondii is needed eagerly. The purpose of the present study is to assess the protective efficacy of a DNA vaccine encoding the T. gondii toxofilin gene (pEGFP-toxofilin). In addition, toxofilin DNA vaccine combined with the individual adjuvants, alum or monophosphoryl lipid A (MPLA), or a mixture of alum-MPLA adjuvant were screened for their ability to enhance antibody responses.MethodsUsing bioinformatics, we analyzed the gene and amino acid sequences of the toxofilin protein, recognizing and identifying several potential linear B and T helper (Th)-1 cell epitopes. BALB/c mice were immunized three times with either toxofilin DNA vaccine alone or in combination with the adjuvants such as alum, MPLA or an alum-MPLA mixture. The systemic immune response was evaluated by cytokine, the percentage of CD4 (+) and CD8 (+) T cells and specific antibody measurement. Two weeks after the last immunization, protective efficacy was evaluated by challenging intraperitoneally with 1 × 104 tachyzoites of T. gondii or intragastrically with 20 cysts of T. gondii PRU strain.ResultsAll experimentally immunized mice developed strong humoral and cellular immune responses compared with the control groups. Moreover, by comparison with the non-adjuvant toxofilin DNA vaccine group, adding alum adjuvant to toxofilin DNA vaccine resulted in an increase in humoral response and a skewed Th2 response. However, the MPLA adjuvant with toxofilin DNA vaccine induced significantly enhanced humoral and Th1-biased immune responses. Importantly, the co-administration of alum-MPLA adjuvant in combination with the toxofilin DNA vaccine shifted the Th2 immune response to a Th1 response compared with the alum-toxofilin group, and elicited the strongest humoral and Th1 responses among all the groups. At the same time, a longer survival time and less cyst amounts against T. gondii infection were also observed in the alum-MPLA-toxofilin group in comparison with single or no adjuvant groups.ConclusionsToxoplasma gondii toxofilin is a promising vaccine candidate that warrants further development. Co-administration of the alum-MPLA adjuvant mixture with DNA vaccine could effectively enhance immunogenicity and strongly skew the cellular immune response towards a Th1 phenotype.
Highlights
A widely prevalent disease, toxoplasmosis poses serious health threats to both humans and animals; development of an ideal DNA vaccine against Toxoplasma gondii is needed eagerly
Bioinformatic analysis The gene and amino acid sequences of toxofilin were identified from GenBank, the primary characteristics of the gene encoding protein were analyzed by ProtParam, the primary amino acid sequences of toxofilin homologs were downloaded from the National
For four different T. gondii strains, the protein sequence alignment is shown in Fig. 1. and share 96.53% similarity, with toxofilin of the T. gondii RH strain sharing 100%, 91.84%, and 94.29% sequence identity with GT1, ME49, and VANDPR strains, respectively
Summary
A widely prevalent disease, toxoplasmosis poses serious health threats to both humans and animals; development of an ideal DNA vaccine against Toxoplasma gondii is needed eagerly. The primary strategy for the treatment of toxoplasmosis is chemical drugs; such drugs have many drawbacks, including poor tolerance, side effects, and the development of drug resistance and are ineffective for the treatment of T. gondii tissue cysts in warmblooded animals. They can’t prevent reinfection [6]. The development of a higher efficacy vaccine remains a vital challenge in light of the persistent nature of chronic toxoplasmosis
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