Abstract
BackgroundToxoplasmosis is a worldwide zoonosis caused by the intracellular parasite Toxoplasma gondii. However, no effective vaccine is yet available. Poly(lactide-co-glycolide) polymers can reduce protein degradation and sustain the release of antigens over a long period, which could generate a long-lasting immune response in vivo. Using a mouse model of toxoplasmosis, we evaluated the protective efficacy of vaccination with two recombinant proteins, which are formulated in biodegradable polymers.MethodsTwo recombinant proteins, rCDPK6 and rROP18, were encapsulated in poly(d,l-lactide-co-glycolide) (PLG), and then injected subcutaneously into Kunming mice. The mice immune responses were evaluated in terms of lympho-proliferation, cytokine expression, and antibodies. The survival of infected mice and brain cyst formation were also evaluated at 6 weeks after challenge with T. gondii RH strain (genotype I) or PRU strain (genotype II).ResultsBoth protein vaccines induced Th1-biased immune responses, with increased specific antibodies and T cells, high levels of interferon-γ and interleukin 2, and strong lymphocyte proliferative responses. The mice immunized with the various protein vaccines survived slightly longer time than the control groups (P > 0.05) after injection with T. gondii RH strain. There were fewer brain cysts in the mice in all the immunized groups than that in the control groups, and the brain cysts were significantly reduced in mice immunized with proteins + 206, rCDPK6 + PLG and rCDPK6 + rROP18 + PLG (P < 0.05) compared controls. Further comparison of the immune responses to the proteins adjuvanted with PLG or Montanide™ ISA 206 VG 6 weeks after the last immunization revealed that antigens encapsulated in PLG conferred greater protective immunity against challenge.ConclusionsThese findings suggest that the two recombinant T. gondii proteins encapsulated in PLG conferred immunity to T. gondii for an extended period, providing the foundation for the further development of a commercial vaccine against toxoplasmosis.
Highlights
Toxoplasmosis is a worldwide zoonosis caused by the intracellular parasite Toxoplasma gondii
Zhang et al BMC Infectious Diseases (2016) 16:168 (Continued from previous page). These findings suggest that the two recombinant T. gondii proteins encapsulated in PLG conferred immunity to T. gondii for an extended period, providing the foundation for the further development of a commercial vaccine against toxoplasmosis
We demonstrated that the TgCDPK1 [26] and TgCDPK3 genes [27] are promising candidates for the development of vaccines against T. gondii infection, and the TgCDPK5 protein elicited only partial protection against chronic parasitic infection [28]
Summary
Toxoplasmosis is a worldwide zoonosis caused by the intracellular parasite Toxoplasma gondii. Using a mouse model of toxoplasmosis, we evaluated the protective efficacy of vaccination with two recombinant proteins, which are formulated in biodegradable polymers. As the most successful parasitic pathogen, Toxoplasma gondii infects a wide range of warm-blooded vertebrate intermediate hosts, including humans [1,2,3]. The parasite is one of the most common pathogens of humans, and nearly one third of the global population is chronically infected [3, 4]. Congenital toxoplasmosis can cause ocular disease, intracranial calcification, hydrocephaly, microcephaly, and psychomotor and mental retardation in infants of women who experienced primary infection with T. gondii during gestation [5,6,7]. The reemergence of food-borne routes of T. gondii transmission to humans has raised public health and food safety concerns in recent years [2, 4, 11]
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