Vaccination against the Intracellular PathogensLeishmania majorandL. amazonensisby Directing CD40 Ligand to Macrophages

Chen, Gang; Darrah, Patricia A.; Mosser, David M.

doi:10.1128/iai.69.5.3255-3263.2001

Cited by 20 publications

(17 citation statements)

References 52 publications

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“…The same thing was reported by Rolph and Kaufmann (2001), Chen et al (2001) and Field et al (2007) which uses a combination of CD40 and vaccine of heat-killed Listeria mononcytogenes and Leishmania major. The development of vaccines based on cell-mediated immunity was also reported by Lawrence et al (2012) in a vaccination using HKSA.…”

Section: Vaccination Based On Cell-mediated Immunitysupporting

confidence: 69%

Staphylococcus aureus Vaccine Candidate from MRSA Isolates: The Prospect of a Multivalent Vaccine

Sandi¹,

Wanahari²,

MacPhillamy³

et al. 2015

American Journal of Infectious Diseases

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Staphylococcus aureus (S. aureus) is a major cause various infections in humans and animals throughout the world. The increasing incidence of S. aureus infection, particularly methicillin-resistant Staphylococcus aureus (MRSA) is complicated by the antibiotic-resistance phenomenon. Thus, it requires new strategies to prevent wider scale of its incidence occurring. Preventative methods against infectious diseases through vaccination can prevent, control and reduce the severity of the disease process. Various methods have been used in the development of vaccines to prevent S. aureus infections, but no satisfactory results have been obtained. Recent studies suggests that multivalent vaccines based on cell-mediated immunity is expected to provide better protection against infection. The purpose of this article is to summarize the challenges of S. aureus infection and the current status of its potential solution with the development of a multivalent vaccine and to explain the latest approaches recommended to obtain successful development of S. aureus vaccine by inducing T-cells CD8+, CD4+ and Th17. Seven MRSA Indonesian origin isolates from humans and dairy-cattle were used as candidate vaccines as genotypic characterization had previously been performed (coa, eta, etb, hla, hlb, cap5, cap8, fnbA, fnbB and mecA). Vaccination can be performed with live-attenuated or killed-vaccine and could be combined with an injection of αCD40 monoclonal-antibodies (mAbs) with the aim to induce cellular-based active immunity (T CD8+, CD4+ and Th17). These isolates are expected to be safe vaccine candidates with immunogenic-protective properties based on genetic and antigenic variation to prevent and control staphylococcal infections in humans and animals.

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Section: Vaccination Based On Cell-mediated Immunitysupporting

confidence: 69%

Staphylococcus aureus Vaccine Candidate from MRSA Isolates: The Prospect of a Multivalent Vaccine

Sandi¹,

Wanahari²,

MacPhillamy³

et al. 2015

American Journal of Infectious Diseases

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“…(4,20,31,41). Previously, we have shown that combining CD40L with leishmanial antigens can improve disease outcome in susceptible animal models (7). Also, vaccination with CD40 ligand trimer DNA was shown to provide protection in the BALB/c host (14).…”

Section: Discussionmentioning

confidence: 99%

“…Animals that were vaccinated with wild-type or transgenic organisms were equally protected against rechallenge, indicating that these organisms, although reduced in virulence, retain immunogenicity required to induce an adaptive immune response. Previous studies in our laboratory demonstrated that the combination of L929 cells expressing CD40L with parasite antigens was able to provide significant protection in the susceptible BALB/c mouse (7). Also, CD40L trimer DNA has been used successfully to vaccinate BALB/c mice against L. major (14).…”

Section: Discussionmentioning

confidence: 99%

“…Anti-CD40 antibodies were also shown to induce macrophage killing of parasites and act synergistically with antimony therapy to improve disease outcome (30). Previously, we demonstrated that the addition of CD40L to leishmanial antigens provided protection against challenge with virulent organisms (7). In addition, CD40L trimer DNA has been successfully used as an adjuvant in the BALB/c model of L. major infection (14).…”

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confidence: 99%

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Reduced Pathology following Infection with TransgenicLeishmania majorExpressing Murine CD40 Ligand

et al. 2007

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Leishmanization is the inoculation of live Leishmania into the host to vaccinate against subsequent infections. This approach has been largely discontinued due to safety concerns. We have previously shown that combining CD40 ligand (CD40L) with Leishmania antigen preferentially induces a type 1 immune response and provides some protection to vaccinated mice (G. Chen, P. A. Darrah, and D. M. Mosser, Infect. Immun. 69:3255-3263, 2001). In the present study, we developed transgenic L. major organisms which express and secrete the extracellular portion of CD40L (L. major CD40LE). We hypothesized that these organisms would be less virulent but more immunogenic than wild-type organisms and therefore be more effective at leishmanization. Transgenic parasites expressing CD40L mRNA and protein were developed. BALB/c mice infected with these parasites developed significantly smaller lesions containing fewer parasites than animals infected with wild-type organisms. Infection of resistant C57BL/6 mice with low doses of transgenic parasites induced a significant amount of protection against subsequent high-dose infection with wild-type organisms. These results demonstrate that transgenic organisms expressing CD40L are less virulent than wild-type organisms while retaining full immunogenicity.

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“…Its role in acquired resistance in leishmaniasis is strongly supported by the ability of CD40L to potentiate vaccine-induced immunity to L. major (11,15) and by the failure of mice with induced or genetic deficiencies in CD40 engagement to control infection, which in each case was associated with impaired production of IL-12 (3,6,18,49). That CD40 ligation alone is insufficient for IL-12 production in vivo has been demonstrated in mice, which required a microbial exposure using a soluble antigen derived from Toxoplasma gondii to produce high levels of the cytokine following treatment with agonistic anti-CD40 antibodies (44).…”

Section: Discussionmentioning

confidence: 99%

LeishmaniaPriming of Human Dendritic Cells for CD40 Ligand-Induced Interleukin-12p70 Secretion Is Strain and Species Dependent

et al. 2002

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A major question in the study of leishmaniasis is what dictates clinical disease expression produced by different Leishmania species, i.e., cutaneous versus systemic and healing versus nonhealing. Animal models using a Leishmania species associated with self-limiting cutaneous disease (L. major) have revealed that protective immunity requires CD40/CD40 ligand (CD40L)-dependent, interleukin-12 (IL-12)-driven Th1 responses. We recently showed that L. major can prime human dendritic cells (DCs) for CD40L-triggered IL12p70 secretion and that these cells can drive a Th1 response in autologous T cells from sensitized individuals. Here we show that in contrast to L. major, Leishmania species responsible for visceral disease (L. donovani), as well as species associated with persistent, cutaneous lesions and occasional systemic disease (L. tropica), did not induce CD40L-dependent IL-12p70 production, despite comparable levels of uptake by DCs. Up-regulated surface expression of CD40 did not correlate with IL-12p70 production, and appreciable CD40L-induced IL-12p40 secretion was observed in uninfected as well as infected DCs, regardless of species. Reverse transcription-PCR analysis confirmed that the production of heterodimeric IL-12 was limited by expression of IL-12p35 mRNA, which was dependent on both a microbial priming signal and CD40 engagement for its high-level induction. The intrinsic differences in the ability of Leishmania species to prime DCs for CD40L-dependent IL-12p70 secretion may account, at least in part, for the evolution of healing and nonhealing forms of leishmanial disease.Leishmaniasis is a vector-borne parasitic disease which, depending mainly upon the species of Leishmania, can display a spectrum of clinical manifestations ranging from localized cutaneous lesions that heal spontaneously to generalized systemic disease with fatal outcome. Regardless of species and clinical outcome, all Leishmania infections are initiated by infectious-stage metacyclic promastigotes which are deposited in the skin following a sand fly bite. These forms are taken up by macrophages and replicate as intracellular amastigotes. The pathology that is typical of localized cutaneous disease is immune mediated and is accompanied by the control of infection in the skin. In contrast, the absence of strong acquired immunity, while moderating the development of dermal pathology, results in parasite dissemination and uncontained parasite growth in liver, spleen,

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Vaccination against the Intracellular PathogensLeishmania majorandL. amazonensisby Directing CD40 Ligand to Macrophages

Cited by 20 publications

References 52 publications

<i>Staphylococcus aureus</i> Vaccine Candidate from MRSA Isolates: The Prospect of a Multivalent Vaccine

<i>Staphylococcus aureus</i> Vaccine Candidate from MRSA Isolates: The Prospect of a Multivalent Vaccine

Reduced Pathology following Infection with TransgenicLeishmania majorExpressing Murine CD40 Ligand

LeishmaniaPriming of Human Dendritic Cells for CD40 Ligand-Induced Interleukin-12p70 Secretion Is Strain and Species Dependent

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