AUTHOR=Li Jixu , Galon Eloiza May , Guo Huanping , Liu Mingming , Li Yongchang , Ji Shengwei , Zafar Iqra , Gao Yang , Zheng Weiqing , Adjou Moumouni Paul Franck , Rizk Mohamed Abdo , Tumwebaze Maria Agnes , Benedicto Byamukama , Ringo Aaron Edmond , Masatani Tatsunori , Xuan Xuenan 

TITLE=PLK:Δgra9 Live Attenuated Strain Induces Protective Immunity Against Acute and Chronic Toxoplasmosis

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.619335

DOI=10.3389/fmicb.2021.619335

ISSN=1664-302X

ABSTRACT=<p>Toxoplasmosis is a zoonotic parasitic disease caused by the obligate intracellular protozoa <italic>Toxoplasma gondii</italic>, which threatens a range of warm-blooded mammals including humans. To date, it remains a challenge to find safe and effective drug treatment or vaccine against toxoplasmosis. In this study, our results found that the development of a mutant strain based on gene disruption of dense granule protein 9 (gra9) in type II PLK strain decreased parasite replication <italic>in vivo</italic>, severely attenuated virulence in mice, and significantly reduced the formation of cysts in animals. Hence, we developed an immunization scheme to evaluate the protective immunity of the attenuated strain of Δ<italic>gra9</italic> in type II PLK parasite as a live attenuated vaccine against toxoplasmosis in the mouse model. Δ<italic>gra9</italic> vaccination-induced full immune responses characterized by significantly high levels of pro-inflammatory cytokine interferon gamma (IFN-γ) and interleukin-12 (IL-12), maintained the high <italic>T. gondii</italic>-specific immunoglobulin G (IgG) level, and mixed high IgG1/IgG2a levels. Their levels provided the complete protective immunity which is a combination of cellular and humoral immunity in mouse models against further infections of lethal doses of type I RH, type II PLK wild-type tachyzoites, or type II PLK cysts. Results showed that Δ<italic>gra9</italic> vaccination proved its immunogenicity and potency conferring 100% protection against acute and chronic <italic>T. gondii</italic> challenges. Together, Δ<italic>gra9</italic> vaccination provided safe and efficient immune protection against challenging parasites, suggesting that <italic>PLK</italic>:Δ<italic>gra9</italic> is a potentially promising live attenuated vaccine candidate.</p>