DNA vaccination with a gene encoding Toxoplasma gondii GRA6 induces partial protection against toxoplasmosis in BALB/c mice

Abstract

BackgroundInfection with the protozoan Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. Protection from acute toxoplasmosis is known to be mediated by CD8+ T cells, but the T. gondii antigens and host genes required for eliciting protective immunity have been poorly defined. The T. gondii dense granule protein 6 (GRA6), recently proved to be highly immunogenic and produces fully immune protection in T. gondii infected BALB/c mice with an H-2Ld gene. The CD8+ T cell response of H-2Ld mice infected by the T. gondii strain seemed to target entirely to a single GRA6 peptide HF10-H-2Ld complex.ResultsTo determine whether a GRA6-based DNA vaccine can elicit protective immune responses to T. gondii in BALB/c mice, we constructed a eukaryotic expression vector pcDNA3.1-HisGRA6 and tested its immunogenicity in a mouse model. BALB/c mice were vaccinated intramuscularly with three doses of GRA6 DNA and then challenged with a lethal dose of T. gondii RH strain tachyzoites. All immunized mice developed high levels of serum anti-GRA6 IgG antibodies, and in vitro splenocyte proliferation was strongly enhanced in mice adjuvanted with levamisole (LMS). Immunization with pcDNA3.1-HisGRA6 with LMS resulted in 53.3% survival of challenged BALB/c mice as compared to 40% survival of BALB/c without LMS. Additionally, immunized Kunming mice without an allele of H-2Ld failed to survive.ConclusionsOur result supports the concept that the acquired immune response is MHC restricted. This study has a major implication for vaccine designs using a single antigen in a population with diverse MHC class I alleles.

Induction of long-lasting protective immunity against Toxoplasma gondii in BALB/c mice by recombinant surface antigen 1 protein encapsulated in poly (lactide-co-glycolide) microparticles

“…DNA vaccination for the induction of both specific humoral and cellular immune responses against a lethal tachyzoite challenge has been studied in mice [31,32]. However, in comparison, PLG-rSAG1 microparticles prepared in the present study provide a much higher protection rate (80%) in BALB/c mice than the GRA6 DNA vaccine (53.3%) [32]. In addition, only survival prolongation (by 18 days), but no protection, has been observed in BALB/c mice immunized with another DNA vaccine, pSAG1/14-3-3 [31].…”

Evaluation of protective immune responses induced by DNA vaccines encoding Toxoplasma gondii surface antigen 1 (SAG1) and 14-3-3 protein in BALB/c mice

“…Preventing tissue cyst formation in animals for consumption can help avoid parasite transmission to humans and animals, which is important in the farming industry [12]. Experimental studies showed that DNA vaccination can induce both survival prolongation and brain cyst reduction in rodents [44,45]. An effective and safe vaccine should protect the hosts against T. gondii infection and reduce the potential risk of tissue cyst generation in intermediate hosts and development of oocysts in cats.…”

Vaccination with toxofilin DNA in combination with an alum-monophosphoryl lipid A mixed adjuvant induces significant protective immunity against Toxoplasma gondii

“…DNA vaccinations against toxoplasmosis are well known to induce Th1 immune response [8]. Several single-antigen vaccines such as ROP8, TgCyP, and GRA6, have been successful in facilitating survival following a lethal dose of infection challenge, with a range of survival rates from 37.5 to 50.0% [9–11]. However, the development of a higher efficacy vaccine remains a vital challenge in light of the persistent nature of chronic toxoplasmosis.…”