Human and Murine Immune Responses to a Novel Leishmania major Recombinant Protein Encoded by Members of a Multicopy Gene Family
John R. Webb,Antonio Campos-Neto,Pamela J. Ovendale,Tricia I. Martin,Erika Jean Stromberg,Roberto Badaró,Steven G. Reed,Steven G. Reed,Steven G. Reed +8 more
TLDR
Immunization of BALB/c mice with recombinant TSA protein resulted in the development of strong cellular immune responses and conferred protective immune responses against infection with L. major, suggesting that the TSA protein may be useful as a component of a subunit vaccine against leishmaniasis.Abstract:
Vaccination of BALB/c mice with Leishmania major promastigote culture filtrate proteins plus Corynebacterium parvum confers resistance to infection with L. major. To define immunogenic components of this protein mixture, we used sera from vaccinated mice to screen an L. major amastigote cDNA expression library. One of the immunoreactive clones thus obtained encoded a novel protein of L. major with a molecular mass of 22.1 kDa. The predicted amino acid sequence of this clone exhibited significant homology to eukaryotic thiol-specific-antioxidant (TSA) proteins. Therefore, we have designated this protein L. major TSA protein. Southern blot hybridization analyses indicate that there are multiple copies of the TSA gene in all species of Leishmania analyzed. Northern blot analyses demonstrated that the TSA gene is constitutively expressed in L. major promastigotes and amastigotes. Recombinant TSA protein containing an amino-terminal six-histidine tag was expressed in Escherichia coli with the pET17b system and was purified to homogeneity by affinity chromatography. Immunization of BALB/c mice with recombinant TSA protein resulted in the development of strong cellular immune responses and conferred protective immune responses against infection with L. major when the protein was combined with interleukin 12. In addition, recombinant TSA protein elicited in vitro proliferative responses from peripheral blood mononuclear cells of human leishmaniasis patients and significant TSA protein-specific antibody titers were detected in sera of both cutaneous-leishmaniasis and visceral-leishmaniasis patients. Together, these data suggest that the TSA protein may be useful as a component of a subunit vaccine against leishmaniasis.read more
Citations
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The immunology of susceptibility and resistance to Leishmania major in mice
TL;DR: Established models of T-helper-2-cell dominance in BALB/c mice infected with Leishmania major — involving the early production of interleukin-4 by a small subset of LeishMania-specific CD4+ T cells — have been refined by accumulating evidence that this response is not sufficient and, under some circumstances, not required to promote susceptibility.
Journal ArticleDOI
Taking toll: lipid A mimetics as adjuvants and immunomodulators.
David H. Persing,Rhea N. Coler,Michael J. Lacy,Johnson David A,Jory R. Baldridge,Robert M. Hershberg,Steven G. Reed +6 more
TL;DR: Preliminary evidence suggests that MLA and a chemically distinct family of lipid A mimetics - the aminoalkyl glucosaminide 4-phosphates - act on Toll-like receptor 4 (TLR4) and have potent immunomodulatory effects when used both as vaccine adjuvants and as stand-alone products.
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Second-generation vaccines against leishmaniasis
Rhea N. Coler,Steven G. Reed +1 more
TL;DR: This article focuses on advances made with second-generation vaccines against leishmaniasis, and identifies several antigens that might be potential vaccine candidates.
Journal ArticleDOI
Adjuvant effect of interleukin-12 in a vaccine against leishmania major
TL;DR: IL-12 is an effective adjuvant for the initiation of protective cell- mediated immunity against leishmaniasis and may be an important component in other vaccines that need to induce cell-mediated immunity.
Journal ArticleDOI
Leish-111f, a Recombinant Polyprotein Vaccine That Protects against Visceral Leishmaniasis by Elicitation of CD4+ T Cells
TL;DR: The Leish-111f+MPL-SE product reported here is the first defined vaccine for leishmaniasis in human clinical trials and has completed phase 1 and 2 safety and immunogenicity testing in normal, healthy human subjects.
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