Immunization with MIC1 and MIC4 induces protective immunity against Toxoplasma gondii

Lourenço, Elaine; Bernardes, Emerson Soares; Silva, Neide M.; Mineo, José Roberto; Panunto-Castelo, Ademílson; Roque-Barreira, Maria Cristina

doi:10.1016/j.micinf.2005.11.013

Cited by 66 publications

(53 citation statements)

References 56 publications

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“…A number of T. gondii antigens have been assessed as vaccine candidates against T. gondii infection. These include the microneme proteins (MIC1, MIC4, and MIC6) (17,22), dense granule proteins (GRA1 to GRA7) (14,19), rhoptry antigens (ROP1 and ROP2) (5,32), the matrix protein MAG1 (7), and surface antigens (SAG1) (19). ROP16 of T. gondii is one of the key virulence factors (25,29), and there have previously been no reported studies evaluating the immunogenicity of T. gondii ROP16.…”

Section: Discussionmentioning

confidence: 99%

Protective Immunity Induced by Toxoplasma gondii Rhoptry Protein 16 against Toxoplasmosis in Mice

Yuan

Zhang

et al. 2011

Clin Vaccine Immunol

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Toxoplasma gondii can infect a large variety of domestic and wild animals and human beings, sometimes causing severe pathology. Rhoptries are involved in T. gondii invasion and host cell interaction and have been implicated as important virulence factors. In this study, we constructed a DNA vaccine expressing rhoptry protein 16 (ROP16) of T. gondii and evaluated the immune responses it induced in Kunming mice. The gene sequence encoding ROP16 was inserted into the eukaryotic expression vector pVAX I. We immunized Kunming mice intramuscularly. After immunization, we evaluated the immune response using a lymphoproliferative assay, cytokine and antibody measurements, and the survival times of mice challenged lethally. The results showed that mice immunized with pVAX-ROP16 developed a high level of specific antibody responses against T. gondii ROP16 expressed in Escherichia coli, a strong lymphoproliferative response, and significant levels of gamma interferon (IFN-␥), interleukin-2 (IL-2), IL-4, and IL-10 production compared with results for other mice immunized with either empty plasmid or phosphate-buffered saline, respectively. The results showed that pVAX-ROP16 induces significant humoral and cellular Th1 immune responses. After lethal challenge, the mice immunized with pVAX-ROP16 showed a significantly (P < 0.05) prolonged survival time (21.6 ؎ 9.9 days) compared with control mice, which died within 7 days of challenge. Our data demonstrate, for the first time, that ROP16 triggers a strong humoral and cellular response against T. gondii and that ROP16 is a promising vaccine candidate against toxoplasmosis, worth further development.

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Section: Discussionmentioning

confidence: 99%

Protective Immunity Induced by Toxoplasma gondii Rhoptry Protein 16 against Toxoplasmosis in Mice

Yuan

Zhang

et al. 2011

Clin Vaccine Immunol

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“…Numerous studies have evaluated responses to vaccines based on protein or DNA components of T. gondii with various degrees of success (1,2,4,5,9,11,22,24,25,28,36,37,40,44,46). Virulent parasite strains, as well as attenuated T. gondii strains, have been paramount in dissecting the immunobiology of host response in regard to understanding adaptive immune responses that may be helpful in vaccine design.…”

mentioning

confidence: 99%

Long-Term Immunity to Lethal Acute or Chronic Type IIToxoplasma gondiiInfection Is Effectively Induced in Genetically Susceptible C57BL/6 Mice by Immunization with an Attenuated Type I Vaccine Strain

Gigley¹,

Fox²,

Bzik³

2009

Infect Immun

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C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized B6 mice chronically infected with ME49 survived for at least 12 months without succumbing to the chronic infection. Potent immunity to type II challenge infections persisted for at least 10 months after vaccination. While the cps1-1 strain-elicited immunity did not prevent the establishment of a chronic infection or clear established brain cysts, cps1-1 strain-elicited CD8؉ immune T cells significantly inhibited recrudescence of brain cysts during chronic ME49 infection. In addition, we show that uracil starvation of the cps1-1 strain induces early markers of bradyzoite differentiation. Collectively, these results suggest that more effective immune control of chronic type II infection in the genetically susceptible B6 background is established by vaccination with the nonreplicating type I uracil auxotroph cps1-1 strain.

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“…In the past few decades, many T. gondii antigens have been assessed as potential vaccine candidates against toxoplasmosis, including the surface antigens (SAG1) (9), dense granule proteins (GRA1 to GRA7) (6), microneme proteins (MIC1, MIC6, and MIC8) (8,10,18), rhoptry antigens (ROP2, ROP16, and ROP18) (22,25,26), and matrix protein MAG1 (2). However, there had been no reported studies evaluating the immunogenicity of T. gondii ROP13.…”

Section: Discussionmentioning

confidence: 99%

Protective Efficacy of a Toxoplasma gondii Rhoptry Protein 13 Plasmid DNA Vaccine in Mice

Wang

Yuan

Petersen

et al. 2012

Clin Vaccine Immunol

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f Toxoplasma gondii is an obligate intracellular parasite infecting humans and other warm-blooded animals, resulting in serious public health problems and economic losses worldwide. Rhoptries are involved in T. gondii invasion and host cell interaction and have been implicated as important virulence factors. In the present study, a DNA vaccine expressing rhoptry protein 13 (ROP13) of T. gondii inserted into eukaryotic expression vector pVAX I was constructed, and the immune protection it induced in Kunming mice was evaluated. Kunming mice were immunized intramuscularly with pVAX-ROP13 and/or with interleukin-18 (IL-18). Then, we evaluated the immune response using a lymphoproliferative assay, cytokine and antibody measurements, and the survival times of mice challenged with the virulent T. gondii RH strain (type I) and the cyst-forming PRU strain (type II). The results showed that pVAX-ROP13 alone or with pVAX/IL-18 induced a high level of specific anti-T. gondii antibodies and specific lymphocyte proliferative responses. Coinjection of pVAX/IL-18 significantly increased the production of gamma interferon (IFN-␥), IL-2, IL-4, and IL-10. Further, challenge experiments showed that coimmunization of pVAX-ROP13 with pVAX/IL-18 significantly (P < 0.05) increased survival time (32.3 ؎ 2.7 days) compared with pVAX-ROP13 alone (24.9 ؎ 2.3 days). Immunized mice challenged with T. gondii cysts (strain PRU) had a significant reduction in the number of brain cysts, suggesting that ROP13 could trigger a strong humoral and cellular response against T. gondii cyst infection and that it is a potential vaccine candidate against toxoplasmosis, which provided the foundation for further development of effective vaccines against T. gondii.

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Immunization with MIC1 and MIC4 induces protective immunity against Toxoplasma gondii

Cited by 66 publications

References 56 publications

Protective Immunity Induced by Toxoplasma gondii Rhoptry Protein 16 against Toxoplasmosis in Mice

Protective Immunity Induced by Toxoplasma gondii Rhoptry Protein 16 against Toxoplasmosis in Mice

Long-Term Immunity to Lethal Acute or Chronic Type IIToxoplasma gondiiInfection Is Effectively Induced in Genetically Susceptible C57BL/6 Mice by Immunization with an Attenuated Type I Vaccine Strain

Protective Efficacy of a Toxoplasma gondii Rhoptry Protein 13 Plasmid DNA Vaccine in Mice

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