Toxoplasma gondii α-amylase deletion mutant is a promising vaccine against acute and chronic toxoplasmosis

Microb Biotechnol. 2020 Nov;13(6):2057-2069. doi: 10.1111/1751-7915.13668. Epub 2020 Sep 22.

Abstract

Individuals with inhibited immunity may develop lethal toxoplasmosis; thus, a safe and effective vaccine is urged to be developed. Toxoplasma gondii (T. gondii) α-amylase (α-AMY) is one of the enzymes responsible for starch digestion. In the present study, we first generated a ME49Δα-amy mutant and discovered that loss of α-AMY robustly grew in vitro but contributed to significant virulence attenuation in vivo. Therefore, we established a mouse model to explore the protective immunity of Δα-amy mutant against acute and chronic toxoplasmosis. The results indicated that the survival rates of short-term or long-term immunized mice re-infected with the tachyzoites of multiple T. gondii strains were nearly 100%. ME49Δα-amy not only could provide protective immunity against tachyzoites infection but also could resist the infection of tissue cysts. Furthermore, we detected that ME49Δα-amy vaccination could effectively eliminate the proliferation of parasites in mice and prevent the formation of cysts. The significant increases of Th1-type cytokines, Th2-type cytokines and specific total IgG and IgG subclasses (IgG2a and IgG1) confirmed efficiency of a combination of cellular and humoral immunity against infection. In conclusion, ME49Δα-amy attenuated strain can produce strong immune responses to provide efficient protection against toxoplasmosis, which signifies that ME49Δα-amy mutant may be a potential vaccine candidate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Cytokines
  • Immunity, Cellular
  • Mice
  • Mice, Inbred BALB C
  • Protozoan Proteins
  • Protozoan Vaccines*
  • Toxoplasma* / genetics
  • Toxoplasmosis* / prevention & control
  • Vaccines, DNA*
  • alpha-Amylases / genetics

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Cytokines
  • Protozoan Proteins
  • Protozoan Vaccines
  • Vaccines, DNA
  • alpha-Amylases