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ABSTRACT
Introduction
Toxoplasma gondii (T.gondii) is a widespread protozoan with significant economic losses and public health importance. But so far, the protective effect of reported DNA-based vaccines fluctuates widely, and no study has demonstrated complete protection.
Areas covered
This review provides an inclusive summary of T. gondii DNA vaccine antigens, adjuvants, and some other parameters. A total of 140 articles from 2000 to 2021 were collected from five databases. By contrasting the outcomes of acute and chronic challenges, we aimed to investigate and identify viable immunological strategies for optimum protection. Furthermore, we evaluated and discussed the impact of several parameters on challenge outcomes in the hopes of developing some recommendations to assist better future horizontal comparisons among research.
Expert opinion
In the coming five years of research, the exploration of vaccine cocktails combining invasion antigens and metabolic antigens with genetic adjuvants or novel DNA delivery methods may offer us desirable protection against this multiple stage of life parasite. In addition to finding a better immune strategy, developing better in silico prediction methods, solving problems posed by variables in practical applications, and gaining a more profound knowledge of T.gondii-host molecular interaction is also crucial towards a successful vaccine.
Article highlights
For sole-gene vaccination, MICs and GRAs are the most promising against acute challenges while ROPs confer the best protection against that of chronic.
For multi-gene vaccination, cocktails with SAGs, GRAs and ROPs perform better in the acute challenge. And cocktails with ROPs, SAGs, GRA7 and T. gondii Profilin can greatly improve cyst reduction in chronic challenges.
In silico analysis can undoubtedly accelerate the exploration of multi-epitope DNA vaccines. However, currently, only a limited impact on further the escalation of survival length after the challenge was observed, and improvement toward a better approach is needed.
Genetic adjuvants (e.g. IL-12, IL-18, A2/B subunits of cholera toxin and Hepatitis B surface antigen) and conventional adjuvants (Levamisole) are of great potential in augmenting the efficacy of T. gondii DNA vaccine.
DNA vaccine delivery by conventional syringe injections is considered to be mediocre in inducing immune responses. Hence, some studies have adapted novel inoculation methods such as gene gun, to optimize the vaccine’s efficacy. Gene gun’s high reproductivity in inducing immune responses is considered to have great potential for future clinical application of DNA vaccination.
The selection of mice strains has a significant influence on the challenge results. Mice strain BALB/c, C3H/HeJ and C57BL/6 are categorized as low, intermediate and high susceptibility to T. gondii infection, respectively. C57BL/6 mice have always observed higher mortality.
Immunization and challenge dose would affect the outcome of the challenge trial with no doubt. Besides dosage, the quality of the plasmid, as well as the parasite vitality, are issues to be concerned.
Declaration of interests
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contributions
All authors have substantially contributed to the conception and design of the review article and interpreting the relevant literature, and been involved in writing the review article or revised it for intellectual content.
Correction Statement
This article has been corrected with minor changes. These changes do not impact the academic content of the article.