GRA24-Based DNA Vaccine Prolongs Survival in Mice Challenged With a Virulent Toxoplasma gondii Strain

Zheng, Bin; Lou, Di; Ding, Jianzu; Zhuo, Xunhui; Ding, Haiyan; Kong, Qingming; Lu, Shaohong

doi:10.3389/fimmu.2019.00418

Cited by 31 publications

(44 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results showed that among the three recombinant proteins, roVP3 induced the highest levels of specific IgG in the serum. IL-2 and INF-γ are mainly secreted by Th1 cells, which promote cellular immune responses and IL-4 and IL-10 are mainly secreted by Th2 cells, which promote humoral immune responses (Wang et al, 2017;Zheng et al, 2019). Comparing SI values and and cytokines, we speculate that roVP2 has a strong effect on cellular immune responses and that roVP3 can induce a strong humoral immune response in the mice, although all the three recombinant proteins could stimulate cellular and humoral immune responses.…”

Section: Discussionmentioning

confidence: 88%

Codon optimization, expression in Escherichia coli, and immunogenicity analysis of deformed wing virus (DWV) structural protein

Fei

Guo

Fan

et al. 2020

PeerJ

View full text Add to dashboard Cite

Background Deformed wing virus (DWV) is a serious threat to honey bees (Apis mellifera) and is considered a major cause of elevated losses of honey bee colonies. However, lack of information on the immunogenicity of DWV structural proteins has hindered the development of effective biocontrol drugs. Methods We optimized the VP1, VP2 and VP3 codons of DWV surface capsid protein genes on the basis of an Escherichia coli codon bias, and the optimized genes of roVP1, roVP2 and roVP3 were separately expressed in E. coli and purified. Next, the three recombinant proteins of roVP1, roVP2 and roVP3 were intramuscularly injected into BALB/c and the immunogenicity was evaluated by the levels of specific IgG and cytokines. Furthermore, anti-roVP-antisera (roVP1 or roVP2 or roVP3) from the immunized mice was incubated with DWV for injecting healthy white-eyed pupae for the viral challenge test, respectively. Results The optimized genes roVP1, roVP2 and roVP3 achieved the expression in E. coli using SDS-PAGE and Western blotting. Post-immunization, roVP2 and roVP3 exhibited higher immunogenicity than roVP1 and stimulated a stronger humoral immune response in the mice, which showed that the recombinant proteins of roVP3 and roVP2 induced a specific immune response in the mice. In the challenge test, data regarding quantitative real-time RT-PCR (qRT-PCR) from challenged pupae showed that the level of virus copies in the recombinant protein groups was significantly lower than that of the virus-only group at 96 h post-inoculation (P < 0.05). Among them, the degree of neutralization using antibodies raised to the recombinant proteins are between approximately 2-fold and 4-fold and the virus copies of the roVP3 group are the lowest in the three recombinant protein groups, which indicated that specific antibodies against recombinant proteins roVP1, roVP2 and roVP3 of DWV could neutralize DWV to reduce the virus titer in the pupae. Collectively, these results demonstrated that the surface capsid protein of DWV acted as candidates for the development of therapeutic antibodies against the virus.

show abstract

Section: Discussionmentioning

confidence: 88%

Codon optimization, expression in Escherichia coli, and immunogenicity analysis of deformed wing virus (DWV) structural protein

Fei

Guo

Fan

et al. 2020

PeerJ

View full text Add to dashboard Cite

show abstract

“…This nding was similar to the results from BALB/c mice immunized with T. gondii exosomes that produced high levels of IFN-γ and IL-12 but no signi cant differences in the levels of IL-4 and IL-10 after T. gondii infection [30]. Pregnant mice immunized with T. gondii GRA17 or GRA24 produced high levels of IL-10, which could modulate the pathological damage in foetal mice induced by a large amount of the Th1 cytokine IFN-γ induced by T. gondii challenge [31,39]. BALB/c mouse vaccination with the recombinant protein rNcSRS2 of N. caninum promoted the upregulation of IL-10 expression [40].…”

Section: Discussionmentioning

confidence: 99%

“…When N. caninum invasion occurs, the parasite can be captured and processed by antigen-presenting cells and then presented to T lymphocytes, which further builds adaptive immunity. When N. caninum invades subsequently, speci c anti-N. caninum 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 [31,32]. Humoural immunity is important in eliminating pathogens, strengthening the elimination of invasive microbes, and building immunological memory to protect against reinfection.…”

Section: Discussionmentioning

confidence: 99%

Protective Immunity Against Neospora Caninum Infection Induced by 14-3-3 Protein in Mice

Zhang

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundNeospora caninum causes infections in a wide range of intermediate hosts and remains a threatening disease worldwide because of the lack of effective drugs and vaccines. Our previous studies demonstrated that N. caninum 14-3-3 protein (Nc14-3-3), which is included in N. caninum extracellular vesicles (NEVs), can induce effective immune responses and stimulate cytokine expression in mouse peritoneal macrophages. However, whether Nc14-3-3 has a protective effect and its mechanisms are poorly understood.MethodsHere, we evaluated immune responses and protective effects of Nc14-3-3 against 2×107 Nc-1 tachyzoites. Antibody (IgG, IgGl and IgG2a) levels and Th1-type (IFN-γ and IL-12) and Th2-type (IL-4 and IL-10) cytokines in mouse serum; survival rates; survival time; and parasite burdens were detected.ResultsIn the present study, the immunostimulatory effect of Nc14-3-3 was confirmed, as it triggered Th1-type cytokine (IFN-γ and IL-12) production in mouse serum two weeks after the final immunization. Moreover, the immunization of C57BL/6 mice with Nc14-3-3 induced high IgG antibody levels and significant increases in CD8+ T lymphocytes in the spleens of mice, indicating that a significant cellular immune response was induced. Mouse survival rates and survival times were significantly prolonged after immunization survival rates were 40% for Nc14-3-3 immunization and 60% for NEV immunization, while mice that received GST, PBS, or blank control all died at 13, 9, and 8 days after intraperitoneal N. caninum challenge. In addition, qPCR analysis indicated that there was a lower parasite burden and milder pathological changes in the mice immunized with Nc14-3-3.ConclusionsOur data demonstrate the vaccination of mice with Nc14-3-3 elicits both cellular and humoural immune responses and provides partial protection against acute neosporosis. Thus, Nc14-3-3 could be an effective antigen candidate for vaccine development for neosporosis.

show abstract

“…Meanwhile, an increase in IL-10 and IL-4 levels was also observed in mice, which received a low dose of lumefantrine ( P ≤ 0.01). IL-10 has a central role in limiting inflammation and inhibiting CD4+ T cell-mediated severe immunopathology (Dupont et al ., 2012), and IL-4 functions to enhance IFN- γ production in the late stage of infection (Zheng et al ., 2019 b ).…”

Section: Discussionmentioning

confidence: 99%

Determination of lumefantrine as an effective drug against Toxoplasma gondii infection – in vitro and in vivo study

et al. 2020

View full text Add to dashboard Cite

Toxoplasma gondii is an obligate intracellular protozoan parasite, which can infect almost all warm-blooded animals, including humans, leading to toxoplasmosis. Currently, the effective treatment for human toxoplasmosis is the combination of sulphadiazine and pyrimethamine. However, both drugs have serious side-effects and toxicity in the host. Therefore, there is an urgent need for the discovery of new anti-T. gondii drugs with high potency and less or no side-effects. Our findings suggest that lumefantrine exerts activity against T. gondii by inhibiting its proliferation in Vero cells in vitro without being toxic to Vero cells (P ≤ 0.01). Lumefantrine prolonged mice infected with T. gondii from death for 3 days at the concentration of 50 μg L−1 than negative control (phosphate-buffered saline treated only), and reduced the parasite burden in mouse tissues in vivo (P ≤ 0.01; P ≤ 0.05). In addition, a significant increase in interferon gamma (IFN-γ) production was observed in high-dose lumefantrine-treated mice (P ≤ 0.01), whereas interleukin 10 (IL-10) and IL-4 levels increased in low-dose lumefantrine-treated mice (P ≤ 0.01). The results demonstrated that lumefantrine may be a promising agent to treat toxoplasmosis, and more experiments on the protective mechanism of lumefantrine should be undertaken in further studies.

show abstract

GRA24-Based DNA Vaccine Prolongs Survival in Mice Challenged With a Virulent Toxoplasma gondii Strain

Cited by 31 publications

References 56 publications

Codon optimization, expression in Escherichia coli, and immunogenicity analysis of deformed wing virus (DWV) structural protein

Codon optimization, expression in Escherichia coli, and immunogenicity analysis of deformed wing virus (DWV) structural protein

Protective Immunity Against Neospora Caninum Infection Induced by 14-3-3 Protein in Mice

Determination of lumefantrine as an effective drug against Toxoplasma gondii infection – in vitro and in vivo study

Contact Info

Product

Resources

About