A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine for use in the prevention of visceral leishmaniasis

Chakravarty, Jaya; Kumar, Subodh; Trivedi, Sonali; Vijay, K.; Singh, Anup; Ashman, Jill A.; Laughlin, Elsa M.; Coler, Rhea N.; Kahn, Stuart J.; Beckmann, Anna Marie; Cowgill, Karen D.; Reed, Steven G.; Sundar, Shyam; Piazza, Franco M.

doi:10.1016/j.vaccine.2011.02.096

Cited by 145 publications

(93 citation statements)

References 26 publications

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“…25 More research is also needed to understand how to deliver defined antigen vaccine candidates to humans to elicit protection associated with a balanced cytokine response. 27,36 Nevertheless, it is clear that there is no shortage of potential vaccine candidates that have been identified through studies in mice and can now be used in human trials, 37,38 including those reported in our study.…”

mentioning

confidence: 79%

Cytokine Responses to Novel Antigens in a Peri-Urban Population in Brazil Exposed to Leishmania infantum chagasi

Stober¹,

Jerônimo²,

Pontes³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. Visceral leishmaniasis (VL) is fatal if untreated, and there are no vaccines for this disease. High levels of CD4-derived interferon-γ (IFN-γ) in the presence of low levels of interleukin-10 (IL-10) predicts vaccine success. Tumor necrosis factor-α (TNF-α) is also important in this process. We characterized human immune responses in three groups exposed to Leishmania infantum chagasi in Brazil: 1) drug-cured VL patients (recovered VL); 2) asymptomatic persons with positive Leishmania-specific delayed-type hypersensitivity skin reactions (DTH+); and 3) DTH-negative household contacts. Magnitude of DTH correlated with crude Leishmania antigen-driven IFN-γ, TNF-α, and IL-5, but not IL-10. DTH+ persons showed equivalent levels of IFN-γ, but higher levels of IL-10, to tryparedoxin peroxidase and Leishmania homolog of receptor for activated C kinase compared with recovered VL patients. The IFN-γ:IL-10 and TNF-α:IL-10 ratios were higher in recovered VL patients than in DTH+ persons. Seven of 11 novel candidates (R71, L37, N52, L302.06, M18, J41, and M22) elicited cytokine responses (36-71% of responders) in recovered VL patients and DTH+ persons. This result confirmed their putative status as cross-species vaccine/immunotherapeutic candidates.

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confidence: 79%

Cytokine Responses to Novel Antigens in a Peri-Urban Population in Brazil Exposed to Leishmania infantum chagasi

Stober¹,

Jerônimo²,

Pontes³

et al. 2012

The American Society of Tropical Medicine and Hygiene

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“…Development of adjuvants that can be used to design safe and effective vaccines, along with the development of defined vaccine candidates for leishmaniasis, could have a major impact on the control of disease. The LmSTI-1, Leif, and TSA antigens, as well as the Leish 111f/MPL-SE candidate [37,38] have been used in several clinical trials, three of which, conducted in the U.S., Colombia, and India, showed acceptable safety and immunogenicity in healthy volunteers, both sero-negative for leishmaniasis, and sero-positive [39][40][41][42]. A Phase 1 safety and immunogenicity study using adenovirus encoding HASPB and KMP11 is planned for 2013 (Kaye, personal communication), so there is encouraging progress based on vaccines utilizing either protein/adjuvant or viral vector.…”

Section: Defined Vaccine Candidatesmentioning

confidence: 99%

Case study for a vaccine against leishmaniasis

Alvar

Croft

Kaye

et al. 2013

Vaccine

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103

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“…Consequently, different leishmaniasis vaccines have been proposed and are at different stages of development (11,12). These include recombinant proteins with antigens like thiol-specific antioxidant (TSA), Leishmania major homolog to eukaryotic stress-inducible protein (LmSTI1), and Leishmania elongation initiation factor (LeIF), and first clinical trials have been conducted to evaluate safety and immunogenicity (13). Other candidate vaccines based, among others, on plasmids or recombinant parasites or formulations with various adjuvants are in the pipeline (14).…”

Section: Introductionmentioning

confidence: 99%

Modular Multiantigen T Cell Epitope–Enriched DNA Vaccine Against Human Leishmaniasis

et al. 2014

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The leishmaniases are protozoal diseases that severely affect large populations in tropical and subtropical regions. There are only limited treatment options and preventative measures. Vaccines will be important for prevention, control and elimination of leishmaniasis, and could reduce the transmission and burden of disease in endemic populations. We report the development of a DNA vaccine against leishmaniasis that induced T cell-based immunity and is a candidate for clinical trials. The vaccine antigens were selected as conserved in various Leishmania species, different endemic regions, and over time. They were tested with T cells from individuals cured of leishmaniasis, and shown to be immunogenic and to induce CD4(+) and CD8(+) T cell responses in genetically diverse human populations of different endemic regions. The vaccine proved protective in a rodent model of infection. Thus, the immunogenicity of candidate vaccine antigens in human populations of endemic regions, as well as proof of principle for induction of specific immune responses and protection against Leishmania infection in mice, provides a viable strategy for T cell vaccine development.

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A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine for use in the prevention of visceral leishmaniasis

Cited by 145 publications

References 26 publications

Cytokine Responses to Novel Antigens in a Peri-Urban Population in Brazil Exposed to Leishmania infantum chagasi

Cytokine Responses to Novel Antigens in a Peri-Urban Population in Brazil Exposed to Leishmania infantum chagasi

Case study for a vaccine against leishmaniasis

Modular Multiantigen T Cell Epitope–Enriched DNA Vaccine Against Human Leishmaniasis

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