A Heterologous Prime‐Boost Vaccination Regimen Using ORFF DNA and Recombinant ORFF Protein Confers Protective Immunity against Experimental Visceral Leishmaniasis

Tewary, Poonam; Jain, Manju; Sahani, Mayurbhai Himatbhai; Saxena, Shailendra K.; Madhubala, Rentala

doi:10.1086/430348

Cited by 51 publications

(33 citation statements)

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“…Immunostimulatory oligodeoxynucleotides have also been used as potent enhancers of protective immunity in mice immunized with rORFF Ag (26,27). Besides this, we have also shown that a heterologous prime-boost vaccination regimen using ORFF DNA and rORFF protein confers protective immunity against visceral leishmaniasis (28). Coexpression of ORFF with IL-12 resulted in protection against challenge with L. donovani (29).…”

Section: Ubiquitin Conjugation Of Open Reading Frame F Dna Vaccine Lementioning

confidence: 69%

Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani

Sharma

Madhubala

2009

The Journal of Immunology

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Resistance of Leishmania donovani to sodium antimony gluconate has become a critical issue in the current, prolonged epidemic in India. Hence, there is an urgent need for a vaccine that is protective against both antimony-susceptible and -resistant strains of L. donovani. The multigene LD1 locus located on chromosome 35 of Leishmania is amplified in ∼15% of the isolates examined. The open reading frame F (ORFF), a potential vaccine candidate against visceral leishmaniasis, is part of the multigene LD1 locus. ORFF was expressed as a chimeric conjugate of ubiquitin to elicit an Ag-specific cell-mediated immune response. Analysis of the cellular immune responses of ubiquitin-conjugated ORFF (UBQ-ORFF) DNA-immunized, uninfected BALB/c mice demonstrated that the vaccine induced enhanced IFN-γ-producing CD4+ and CD8+ T cells compared with nonubiquitinated ORFF DNA vaccine. Higher levels of IL-12 and IFN-γ and the low levels of IL-4 and IL-10 further indicated that the immune responses with UBQ-ORFF were mediated toward the Th1 rather than Th2 type. Infection of immunized mice with either the antimony-susceptible (AG83) or -resistant (GE1F8R) L. donovani strain showed that UBQ-ORFF DNA vaccine induced higher protection when compared with ORFF DNA. UBQ-ORFF DNA-immunized and -infected mice showed a significant increase in IL-12 and IFN-γ and significant down-regulation of IL-10. High levels of production of nitrite and superoxide, two macrophage-derived oxidants that are critical in controlling Leishmania infection, were observed in protected mice. The feasibility of using ubiquitinated-conjugated ORFF DNA vaccine as a promising immune enhancer for vaccination against both antimony-susceptible and -resistant strains of L. donovani is reported.

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Section: Ubiquitin Conjugation Of Open Reading Frame F Dna Vaccine Lementioning

confidence: 69%

Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani

Sharma

Madhubala

2009

The Journal of Immunology

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“…Vaccination studies of ORFF protein mainly restricted to murine visceral leishmaniasis. Immunization of mice with recombinant ORFF protein in combination with CpG-ODN conferred significant protection against L. donovani infection with enhanced production of IgG2a and IFN-γ [222,223] but the protein alone induced only partial protection [223,224]. Further, the use of IL-12 DNA as an adjuvant with recombinant ORFF protein induced significant protection correlated with increased proliferative response of splenocytes and subsequent release of Th1 cytokine IFN-γ [225].…”

Section: Orffmentioning

confidence: 99%

Vaccine candidates for leishmaniasis: A review

Nagill

Kaur

2011

International Immunopharmacology

111

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“…There is also progress in characterization of defined antigens protective against VL in animal models as sub-unit or DNA vaccines such as KMP11, HASPB, A2 and CPB [21][22][23][24][25][26][27], whereas there are still only a limited number of bona fide vaccine candidates to combat this disease and no vaccine is available for human use yet. We have recently identified a number of L. infantum Ags by serological screening using sera from L. infantum-infected hamsters [28].…”

Section: Introductionmentioning

confidence: 99%

Protective immunization against visceral leishmaniasis using Leishmania sterol 24-c-methyltransferase formulated in adjuvant

Goto

Bogatzki

Bertholet

et al. 2007

Vaccine

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We present here the identification and characterization of Leishmania sterol 24-c-methyltransferase (SMT), as well as data on protection of mice immunized with this Ag formulated in MPL ® -SE. Serological evaluation revealed that SMT is recognized by VL patients. C57BL/6 mice immunized with this vaccine candidate plus MPL ® -SE showed Ag-specific Th1 immune responses characterized by robust production of IFN-γ upon specific Ag re-exposure in vitro. Upon challenge with L. infantum, mice immunized with SMT plus MPL ® -SE showed significant lower parasite burdens in both spleens and livers compared with non-immunized mice or mice injected with adjuvant alone. The results indicate that SMT/MPL ® -SE can be an effective vaccine candidate for use against VL.

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A Heterologous Prime‐Boost Vaccination Regimen Using ORFF DNA and Recombinant ORFF Protein Confers Protective Immunity against Experimental Visceral Leishmaniasis

Abstract: The heterologous prime-boost vaccination strategy may be utilized for visceral leishmaniasis.

Cited by 51 publications

References 46 publications

Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani

Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains ofLeishmania donovani

Vaccine candidates for leishmaniasis: A review

Protective immunization against visceral leishmaniasis using Leishmania sterol 24-c-methyltransferase formulated in adjuvant

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