Immune responses and protection after DNA vaccination againstToxoplasma gondiicalcium-dependent protein kinase 2 (TgCDPK2)

Abstract

Toxoplasma gondii, an intracellular zoonotic protozoan parasite, is possibly the most widespread parasite of warm-blooded animals and can cause serious public health problems and economic losses worldwide. TgCDPK2, a member of the T. gondii calcium-dependent protein kinase family, was recently identified as an essential regulator for viable cyst development in T. gondii. In the present study, we evaluated the protective immunity induced by DNA vaccination based on a recombinant eukaryotic plasmid, pVAX-TgCDPK2, against acute toxoplasmosis in mice. BALB/c mice were intramuscularly immunized with pVAX-TgCDPK2 plasmid and then challenged by infection with the highly virulent RH strain of T. gondii. The specific immune responses and protective efficacy against T. gondii were analyzed by cytokine and serum antibody measurements, lymphocyte proliferation assays, flow cytometric on lymphocytes and the survival time of mice after challenge. Our results showed that mice immunized with pVAX-TgCDPK2 could elicit special humoral and cellular responses, with higher levels of IgG antibody, and increased levels of Th1-type cytokines IFN-γ, IL-12(p70), and CD3 + CD4 + CD8 − and CD3 + CD8 + CD4 − T cells, and had a prolonged survival time (14.0 ± 2.32 days) compared to control mice. These results demonstrate that pVAX-TgCDPK2 is a potential vaccine candidate against acute toxoplasmosis.

Evaluation of Protective Immune Response Induced by a DNA Vaccine Encoding GRA8 against Acute Toxoplasmosis in a Murine Model

“…When T. gondii invasion occurs for the first time in vivo, the parasite can be captured and processed by antigen-presenting cells and then presented to T lymphocytes, which further build adaptive immunity. When T. gondii invades subsequently, special anti- T. gondii IgG antibodies adhere to the surfaces of the parasites and limit their spread by preventing attachment to host cell receptors, resulting in their elimination by macrophages [ 36 ]. Therefore, humoral response, by promoting macrophages to kill intracellular parasites, has been considered to be of great importance in immunity against T. gondii infection.…”

Calcium-dependent protein kinases are potential targets forToxoplasma gondiivaccine

“…CDPKs not expressed by mammals and fungi which indicates validated targets that can be exploited for a promising target vaccine candidate against toxoplasmosis and anti- T. gondii drugs [ 52 53 54 55 56 ]. Out of 14 CDPKs present in T. gondii , CDPK1, CDPK3, CDPK4, CDPK5, CDPK6, and CDPK7 are the only CDPKs which expressed and conserved in almost all apicomplexan parasites [ 49 57 58 ]. The specific features and main functions of some CDPKs have been embedded in Table 1 .…”

“…Although, as it is well established CD8 + T cell and IFN-γ are obvious to be more fundamental to restrict toxoplasmosis [ 33 ]. Recently, was shown that DNA vaccination with CDPK1, CDPK2, CDPK3, and CDPK5 dramatically increased the number of CD4 + and/or CD8 + T cells in immunized mice [ 52 54 55 56 58 ].…”

“…There are several limitations affecting the immune efficacy of DNA vaccines, which occasionally confined the immunogenicity of them such as dosages of inoculum and the delivery route [ 62 ]; however, 100 µg of the plasmid are routinely injected intramuscularly in mice [ 52 54 55 56 58 ]. It should be noted, following the inoculation, the naked DNA poorly distributed and rapidly degraded by lysosomes and DNAses, thereby, reduce the expression of plasmid DNA [ 72 73 74 ].…”

Avaliação funcional de Toll-Like Receptor 4 (TLR4) em células trofoblásticas humanas vilosa/extravilosa e em vilos placentários humanos de terceiro trimestre gestacional infectados por Toxoplasma gondii

“…A maneira de transmissão varia de acordo com as características físicas e com os hábitos higiênicos da população local. Os humanos adquirem T. gondii pela ingestão de carne crua ou malcozida de bovinos, caprinos, suínos ou aves contendo cistos teciduais, contato com fezes de felídeos contaminados por oocistos, através da ingestão de água ou alimentos contaminados também por oocistos, por transplantes de órgãos ou por transmissão vertical das formas taquizoítos (HILL;DUBEY 2002;GANGNEUX, 2012;CHEN et al, 2017).…”