Prime and boost immunization with influenza and adenovirus encoding the Toxoplasma gondii surface antigen 2 (SAG2) induces strong protective immunity

Machado, Alexandre Vaz; Caetano, Bráulia Costa; Polidoro, Rafael B.; Salgado, Ana Paula C.; Rabelo, Renata H.; Garcia, Cristiana C.; Bruna-Romero, Oscar; Escriou, Nicolas; Gazzinelli, Ricardo T.

doi:10.1016/j.vaccine.2010.02.003

Cited by 44 publications

(36 citation statements)

References 66 publications

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“…Primary infection with T. gondii results in a strong and persistent Th1-type immune response, defined by the high level of IgG antibody response and large amounts of cytokines, which are essential for the control of infection [48,49]. Their findings have suggested that a good immunization protocol should be able to direct the T-helper cells toward a Th1 rather than a Th2-type response [50].…”

Section: Discussionmentioning

confidence: 99%

DNA prime and peptide boost immunization protocol encoding the Toxoplasma gondii GRA4 induces strong protective immunity in BALB/c mice

et al. 2013

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BackgroundToxoplasma gondii is a widespread intracellular parasite, which infects most vertebrate animal hosts and causes zoonotic infection in humans. Vaccine strategy remains a promising method for the prevention and control of toxoplasmosis. T. gondii GRA4 protein has been identified as a potential candidate for vaccine development. In our study, we evaluated the immune response induced by four different immunization vaccination strategies encoding TgGRA4.MethodsBALB/c mice were intramuscularly (i.m.) immunized four times according to specific immunization schedules. Generally, mice in experimental groups were immunized with polypeptide, pGRA4, peptide/DNA, or DNA/peptide, and mice in the control groups were injected with PBS or pEGFP. After immunization, the levels of IgG antibodies and cytokine productions were determined by enzyme-linked immunosorbent assays (ELISA). The survival time of mice was also evaluated after challenge infection with the highly virulent T. gondii RH strain.ResultsThe results showed that mice vaccinated with different immunization regimens (polypeptide, pGRA4, peptide/DNA, or DNA/peptide) elicited specific humoral and cellular responses, with high levels of total IgG, IgG2a isotype and gamma interferon (IFN-γ), which suggested a specific Th1 immunity was activated. After lethal challenge, an increased survival time was observed in immunized mice (11.8 ± 4.8 days) compared to the control groups injected with PBS or pEGFP (P < 0.05). Mice injected with PBS or pEGFP died within 8 days, and there was no significant difference in the protection level in two groups (P > 0.05).ConclusionsThese results demonstrated that this DNA prime and peptide boost immunization protocol encoding the TgGRA4 can elicit the highest level of humoral and cellular immune responses compared to other immunized groups, which is a promising approach to increase the efficacy of DNA immunization.

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Section: Discussionmentioning

confidence: 99%

DNA prime and peptide boost immunization protocol encoding the Toxoplasma gondii GRA4 induces strong protective immunity in BALB/c mice

et al. 2013

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“…For stimulation, a final concentration of 10 µg/ml of nucleoprotein (NP) of PR8 ASNENMETM peptide (NP; amino acids 366-374; for H-2K b ) was added. ELISPOT assay were performed essentially as previously described [53]. The spots were counted on ImmunoSpot S5 Core Analyzer (CTL).…”

Section: Methodsmentioning

confidence: 99%

Protective Immunity and Safety of a Genetically Modified Influenza Virus Vaccine

et al. 2014

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Recombinant influenza viruses are promising viral platforms to be used as antigen delivery vectors. To this aim, one of the most promising approaches consists of generating recombinant viruses harboring partially truncated neuraminidase (NA) segments. To date, all studies have pointed to safety and usefulness of this viral platform. However, some aspects of the inflammatory and immune responses triggered by those recombinant viruses and their safety to immunocompromised hosts remained to be elucidated. In the present study, we generated a recombinant influenza virus harboring a truncated NA segment (vNA-Δ) and evaluated the innate and inflammatory responses and the safety of this recombinant virus in wild type or knock-out (KO) mice with impaired innate (Myd88 -/-) or acquired (RAG -/-) immune responses. Infection using truncated neuraminidase influenza virus was harmless regarding lung and systemic inflammatory response in wild type mice and was highly attenuated in KO mice. We also demonstrated that vNA-Δ infection does not induce unbalanced cytokine production that strongly contributes to lung damage in infected mice. In addition, the recombinant influenza virus was able to trigger both local and systemic virus-specific humoral and CD8+ T cellular immune responses which protected immunized mice against the challenge with a lethal dose of homologous A/PR8/34 influenza virus. Taken together, our findings suggest and reinforce the safety of using NA deleted influenza viruses as antigen delivery vectors against human or veterinary pathogens.

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“…The immune responses elicited by vaccination with SAG2 have previously been demonstrated to protect mice against tachyzoite infection (Yang et al 2003;Jongert et al 2009;Meng et al 2012;Chuang et al 2013a, b) and cyst formation (Mishima et al 2001;Machado et al 2010). In addition, the SAG2 sequence was cloned in our previous work to produce a recombinant SAG2 (rSAG2) protein (Yang et al 2004).…”

mentioning

confidence: 99%

Sustained release of recombinant surface antigen 2 (rSAG2) from poly(lactide-co-glycolide) microparticles extends protective cell-mediated immunity against Toxoplasma gondii in mice

Chuang

Yang

2014

Parasitology

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SUMMARY Current development efforts of subunit vaccines against Toxoplasma gondii, the aetiological agent of toxoplasmosis, have been focused mainly on tachyzoite surface antigens (SAGs) such as SAG2, due to their attachment roles in the process of host-cell invasion. In the present study, we aimed to produce poly(lactide-co-glycolide) (PLG) microparticles (MPs) containing recombinant SAG2 (rSAG2) to induce improved immunity against T. gondii. The resulting PLG-encapsulated rSAG2 (PLG-rSAG2) MPs, 2·14-3·63 μm in diameter, showed 74-80% entrapment efficiency and gradually released antigenic rSAG2 protein (88·3% of the total protein load) for a long 33-day period. Peritoneal immunization with PLG-rSAG2 MPs in BALB/c mice resulted in not only sustained (10 weeks) lymphocyte proliferation and IFN-γ production but also an improved protective capacity (87%) against a lethal subcutaneous challenge of 1×104 live tachyzoites of T. gondii (RH strain). In conclusion, the sustained release of rSAG2 protein from PLG-rSAG2 MPs extends Th1 cell-mediated immunity (lymphocyte proliferation and IFN-γ production) and induces improved protection against T. gondii tachyzoite infection in mice.

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Prime and boost immunization with influenza and adenovirus encoding the Toxoplasma gondii surface antigen 2 (SAG2) induces strong protective immunity

Cited by 44 publications

References 66 publications

DNA prime and peptide boost immunization protocol encoding the Toxoplasma gondii GRA4 induces strong protective immunity in BALB/c mice

DNA prime and peptide boost immunization protocol encoding the Toxoplasma gondii GRA4 induces strong protective immunity in BALB/c mice

Protective Immunity and Safety of a Genetically Modified Influenza Virus Vaccine

Sustained release of recombinant surface antigen 2 (rSAG2) from poly(lactide-co-glycolide) microparticles extends protective cell-mediated immunity against Toxoplasma gondii in mice

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