Protection against LethalNeospora caninumInfection in Mice Induced by Heterologous Vaccination with amic1 mic3KnockoutToxoplasma gondiiStrain

Penarete-Vargas, Diana Marcela; Mévélec, Marie Noëlle; Dion, Sarah; Sèche, Edouard; Dimier‐Poisson, Isabelle; Fandeur, Thierry

doi:10.1128/iai.00703-09

Cited by 17 publications

(5 citation statements)

References 42 publications

(43 reference statements)

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“…Despite considerable efforts, there is currently no effective vaccine against neosporosis on the market. Experimental live vaccines comprised of attenuated N. caninum strains exhibited promising efficacy in pregnant mice and cattle [27][28][29][30][31], while classical subunit vaccines composed of recombinant antigens showed rather limited efficacy [2,32,33]. However, the pharmaceutical industry appears reluctant to invest in a product with a limited shelf life, high production costs, and uncertainty about development of virulence [34].…”

Section: Discussionmentioning

confidence: 99%

A Listeria monocytogenes-Based Vaccine Formulation Reduces Vertical Transmission and Leads to Enhanced Pup Survival in a Pregnant Neosporosis Mouse Model

et al. 2021

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The apicomplexan parasite Neospora caninum is the worldwide leading cause of abortion and stillbirth in cattle. An attenuated mutant Listeria monocytogenes strain (Lm3Dx) was engineered by deleting the virulence genes actA, inlA, and inlB in order to avoid systemic infection and to target the vector to antigen-presenting cells (APCs). Insertion of sag1, coding for the major surface protein NcSAG1 of N. caninum, yielded the vaccine strain Lm3Dx_NcSAG1. The efficacy of Lm3Dx_NcSAG1 was assessed by inoculating 1 × 105, 1 × 106, or 1 × 107 CFU of Lm3Dx_NcSAG1 into female BALB/c mice by intramuscular injection three times at two-week intervals, and subsequent challenge with 1 × 105N. caninum tachyzoites of the highly virulent NcSpain-7 strain on day 7 of pregnancy. Dose-dependent protective effects were seen, with a postnatal offspring survival rate of 67% in the group treated with 1 × 107 CFU of Lm3Dx_NcSAG1 compared to 5% survival in the non-vaccinated control group. At euthanasia (25 days post-partum), IgG antibody titers were significantly decreased in the groups receiving the two higher doses and cytokines recall responses in splenocyte culture supernatants (IFN-γ, IL-4, and IL-10) were increased in the vaccinated groups. Thus, Lm3Dx_NcSAG1 induces immune-protective effects associated with a balanced Th1/Th2 response in a pregnant neosporosis mouse model and should be further assessed in ruminant models.

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Section: Discussionmentioning

confidence: 99%

A Listeria monocytogenes-Based Vaccine Formulation Reduces Vertical Transmission and Leads to Enhanced Pup Survival in a Pregnant Neosporosis Mouse Model

et al. 2021

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“…However, this important stage has scarcely been investigated as an oral infectious material because the tachyzoite is sensitive to gastric juice. It has been reported that tachyzoites can infect cats and mice via the oral route [ 9 , 34 ]. In our previous studies, we have successfully established that tachyzoites infected a mouse model via the oral route [ 45 , 47 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

RecombinantToxoplasma gondiiphosphoglycerate mutase 2 confers protective immunity against toxoplasmosis in BALB/c mice

et al. 2016

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Toxoplasmosis is one of the most widespread zoonoses worldwide. It has a high incidence and can result in severe disease in humans and livestock. Effective vaccines are needed to limit and prevent infection with Toxoplasma gondii. In this study, we evaluated the immuno-protective efficacy of a recombinant Toxoplasma gondii phosphoglycerate mutase 2 (rTgPGAM 2) against T. gondii infection in BALB/c mice. We report that the mice nasally immunised with rTgPGAM 2 displayed significantly higher levels of special IgG antibodies against rTgPGAM 2 (including IgG1, IgG2a and IgAs) and cytokines (including IFN-γ, IL-2 and IL-4) in their blood sera and supernatant of cultured spleen cells compared to those of control animals. In addition, an increased number of spleen lymphocytes and enhanced lymphocyte proliferative responses were observed in the rTgPGAM 2-immunised mice. After chronic infection and lethal challenge with the highly virulent T. gondii RH strain by oral gavage, the survival time of the rTgPGAM 2-immunised mice was longer (P < 0.01) and the survival rate (70%) was higher compared with the control mice (P < 0.01). The reduction rate of brain and liver tachyzoites in rTgPGAM 2-vaccinated mice reached approximately 57% and 69% compared with those of the control mice (P < 0.01). These results suggest that rTgPGAM 2 can generate protective immunity against T. gondii infection in BALB/c mice and may be a promising antigen in the further development of an effective vaccine against T. gondii infection.

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“…While vaccination with T. gondii failed to prevent fetal transmission after N. caninum challenge in sheep [ 27 ], heterologuous vaccination using a T. gondii Mic1-Mic3-KO strain conferred protection against lethal challenge of N. caninum in mice by both oral and intraperitoneal vaccination routes with 80% and 70% survival rates, respectively. Interestingly, immunization of the mice with the Nc-1 strain conferred the same level of protection when administered orally (70% of survivors), whereas none of the mice that were injected intraperitoneally survived [ 65 ]. However, the genotypes of all these parasite populations are not well defined, and the risks associated with using live parasite populations as live vaccines in cattle may be significant, as there is the concern that these organisms might reverse to a disease-causing phenotype.…”

Section: Vaccines Against Neosporosismentioning

confidence: 99%

Vaccines against a Major Cause of Abortion in Cattle, Neospora caninum Infection

Monney

Debache

Hemphill

2011

Animals

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Simple SummaryWe review the efforts to develop a vaccine against neosporosis, caused by the apicomplexan parasite Neospora caninum. Vertical transmission is the main mode of infection, and can lead to stillbirth, abortion, or birth of weak calves. We provide information on the biology of Neospora caninum and on the disease caused by this parasite, and summarize the current understanding on how the host deals with infection. We review studies on live- and subunit-vaccines, and demonstrate advantages and setbacks in the use of small laboratory animal models in investigations on a disease with high relevance in cattle.AbstractNeosporosis, caused by the apicomplexan parasite Neospora caninum, represents one of the economically most important causes of abortion in cattle. During pregnancy, the parasite infects the placental tissue and the fetus, which can lead to stillbirth, abortion, or birth of weak calves. Alternatively, calves are born without clinical symptoms, but they can carry over the parasite to the next generation. In addition, N. caninum causes neuromuscular disease in dogs. The economic importance of neosporosis has prompted researchers to invest in the development of measures to prevent infection of cattle by vaccination. A good vaccine must stimulate protective cellular immune responses as well as antibody responses at mucosal sites and, systemically, must activate T-helper cells to produce relevant cytokines, and must elicit specific antibodies that aid in limiting parasite proliferation, e.g., by interference with host cell invasion, activation of complement, and/or opsonization of parasites to have them killed by macrophages. Different types of vaccines have been investigated, either in bovines or in the mouse model. These include live vaccines such as naturally less virulent isolates of N. caninum, attenuated strains generated by irradiation or chemical means, or genetically modified transgenic strains. Live vaccines were shown to be very effective; however, there are serious disadvantages in terms of safety, costs of production, and stability of the final product. Subunit vaccines have been intensively studied, as they would have clear advantages such as reduced costs in production, processing and storage, increased stability and shelf life. The parasite antigens involved in adhesion and invasion of host cells, such as surface constituents, microneme-, rhoptry- and dense granule-components represent interesting targets. Subunit vaccines have been applied as bacterially expressed recombinant antigens or as DNA vaccines. Besides monovalent vaccines also polyvalent combinations of different antigens have been used, providing increased protection. Vaccines have been combined with immunostimulating carriers and, more recently, chimeric vaccines, incorporating immuno-relevant domains of several antigens into a single protein, have been developed.

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Protection against LethalNeospora caninumInfection in Mice Induced by Heterologous Vaccination with amic1 mic3KnockoutToxoplasma gondiiStrain

Cited by 17 publications

References 42 publications

A Listeria monocytogenes-Based Vaccine Formulation Reduces Vertical Transmission and Leads to Enhanced Pup Survival in a Pregnant Neosporosis Mouse Model

A Listeria monocytogenes-Based Vaccine Formulation Reduces Vertical Transmission and Leads to Enhanced Pup Survival in a Pregnant Neosporosis Mouse Model

RecombinantToxoplasma gondiiphosphoglycerate mutase 2 confers protective immunity against toxoplasmosis in BALB/c mice

Vaccines against a Major Cause of Abortion in Cattle, Neospora caninum Infection

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