Nonreplicating cyst-defective type II Toxoplasma gondii vaccines stimulate protective immunity to acute and chronic infection

Infect Immun. 2015 Mar 16. pii: IAI.02756-14. [Epub ahead of print]

 

Fox BA¹, Bzik DJ¹.

 

Live attenuated vaccine strains such as type I nonreplicating uracil auxotroph mutants are highly effective in eliciting life-long immunity to virulent acute infection by Toxoplasma gondii. However, it is currently unknown whether vaccine elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δku80 genetic background by targeting the deletion of the orotidine 5' -monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication, loss of virulence in mice, and loss of the ability to develop cysts and chronic infection. Vaccination of mice using type II Δku80Δompdc mutants stimulated a fully protective CD8⁺ T cell dependent immunity that prevented acute infection by type I and type II strains of T. gondii, and this vaccination also severely reduced or prevented cyst formation after type II challenge infection. Nonreverting, nonreplicating, and non-cyst forming Δompdc mutants provide new tools to examine protective immune responses elicited by vaccination with a live attenuated type II vaccine.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.

PMID:

25776745

[PubMed - as supplied by publisher]