Leishmaniasis Vaccines: Applications of RNA Technology and Targeted Clinical Trial Designs

Duthie, Malcolm S.; Machado, Bruna Aparecida Souza; Badaró, Roberto; Kaye, Paul M.; Reed, Steven G.

doi:10.3390/pathogens11111259

Cited by 5 publications

(3 citation statements)

References 88 publications

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“…Over the years, a wide array of vaccine strategies have been evaluated against Leishmania parasites with different proven efficacies [14,28,29]. However, several factors have precluded the advancement of more than a few Leishmania-targeting vaccines into clinical trials [28,30]. Leishmaniases cover a wide range of clinical manifestations dependent upon the infecting parasite species.…”

Section: Discussionmentioning

confidence: 99%

A Tailored Approach to Leishmaniases Vaccination: Comparative Evaluation of the Efficacy and Cross-Protection Capacity of DNA vs. Peptide-Based Vaccines in a Murine Model

Mas

Hurtado-Morillas

Martínez‐Rodrigo

et al. 2023

IJMS

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Zoonotic leishmaniases are a worldwide public health problem for which the development of effective vaccines remains a challenge. A vaccine against leishmaniases must be safe and affordable and should induce cross-protection against the different disease-causing species. In this context, the DNA vaccine pHisAK70 has been demonstrated to induce, in a murine model, a resistant phenotype against L. major, L. infantum, and L. amazonensis. Moreover, a chimeric multiepitope peptide, HisDTC, has been obtained by in silico analysis from the histone proteins encoded in the DNA vaccine and has showed its ability to activate a potent CD4+ and CD8+ T-cell protective immune response in mice against L. infantum infection. In the present study, we evaluated the plasmid DNA vaccine pHisAK70 in comparison with the peptide HisDTC (with and without saponin) against L. major and L. infantum infection. Our preliminary results showed that both formulations were able to induce a potent cellular response leading to a decrease in parasite load against L. infantum. In addition, the DNA candidate was able to induce better lesion control in mice against L. major. These preliminary results indicate that both strategies are potentially effective candidates for leishmaniases control. Furthermore, it is important to carry out such comparative studies to elucidate which vaccine candidates are the most appropriate for further development.

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Section: Discussionmentioning

confidence: 99%

A Tailored Approach to Leishmaniases Vaccination: Comparative Evaluation of the Efficacy and Cross-Protection Capacity of DNA vs. Peptide-Based Vaccines in a Murine Model

Mas

Hurtado-Morillas

Martínez‐Rodrigo

et al. 2023

IJMS

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“…RNA vaccine technology has the potential to offer an effective and practical solution to vaccine development. Development of RNA vaccine requires only knowledge of the target gene sequence, eliminating the need for pathogen culture or scale-up recombinant protein production [ 101 ].…”

Section: Vaccination Strategies In Leishmaniasismentioning

confidence: 99%

Leishmania Vaccines: the Current Situation with Its Promising Aspect for the Future

Dinc¹

2022

Korean J Parasitol

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Leishmaniasis is a serious parasitic disease caused by Leishmania spp. transmitted through sandfly bites. This disease is a major public health concern worldwide. It can occur in 3 different clinical forms: cutaneous, mucocutaneous, and visceral Leishmaniasis (CL, MCL, and VL, respectively), caused by different Leishmania spp. Currently, licensed vaccines are unavailable for the treatment of human Leishmaniasis. The treatment and prevention of this disease rely mainly on chemotherapeutics, which are highly toxic and have an increasing resistance problem. The development of a safe, effective, and affordable vaccine for all forms of vector-borne disease is urgently needed to block transmission of the parasite between the host and vector. Immunological mechanisms in the pathogenesis of Leishmaniasis are complex. IL-12-driven Th1-type immune response plays a crucial role in host protection. The essential purpose of vaccination is to establish a protective immune response. To date, numerous vaccine studies have been conducted using live/attenuated/killed parasites, fractionated parasites, subunits, recombinant or DNA technology, delivery systems, and chimeric peptides. Most of these studies were limited to animals. In addition, standardization has not been achieved in these studies due to the differences in the virulence dynamics of the Leishmania spp. and the feasibility of the adjuvants. More studies are needed to develop a safe and effective vaccine, which is the most promising approach against Leishmania infection.

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“…Lm Cen −/− cultures have been produced under GMP conditions, and phase I trials are being planned in the USA and India. The use of mRNA vaccine platforms for leishmaniasis has not been explored yet ( 13 ), but mRNA vaccines encoding Leishmania recombinant LEISH-F2 and LEISH-F3 antigens are in the late preclinical evaluation stage. This mRNA vaccine builds upon the promising outcomes observed in human efficacy trials of the LEISH-F1, F2, and F3 vaccines.…”

Section: Introductionmentioning

confidence: 99%

Memory T cells: promising biomarkers for evaluating protection and vaccine efficacy against leishmaniasis

Nateghi-Rostami,

Sohrabi

2024

Front. Immunol.

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Understanding the immune response to Leishmania infection and identifying biomarkers that correlate with protection are crucial for developing effective vaccines. One intriguing aspect of Leishmania infection is the persistence of parasites, even after apparent lesion healing. Various host cells, including dendritic cells, fibroblasts, and Langerhans cells, may serve as safe sites for latent infection. Memory T cells, especially tissue-resident memory T cells (TRM), play a crucial role in concomitant immunity against cutaneous Leishmania infections. These TRM cells are long-lasting and can protect against reinfection in the absence of persistent parasites. CD4+ TRM cells, in particular, have been implicated in protection against Leishmania infections. These cells are characterized by their ability to reside in the skin and rapidly respond to secondary infections by producing cytokines such as IFN-γ, which activates macrophages to kill parasites. The induction of CD4+ TRM cells has shown promise in experimental immunization, leading to protection against Leishmania challenge infections. Identifying biomarkers of protection is a critical step in vaccine development and CD4+ TRM cells hold potential as biomarkers, as their presence and functions may correlate with protection. While recent studies have shown that Leishmania-specific memory CD4+ T-cell subsets are present in individuals with a history of cutaneous leishmaniasis, further studies are needed to characterize CD4+ TRM cell populations. Overall, this review highlights the importance of memory T cells, particularly skin-resident CD4+ TRM cells, as promising targets for developing effective vaccines against leishmaniasis and as biomarkers of immune protection to assess the efficacy of candidate vaccines against human leishmaniasis.

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Leishmaniasis Vaccines: Applications of RNA Technology and Targeted Clinical Trial Designs

Cited by 5 publications

References 88 publications

A Tailored Approach to Leishmaniases Vaccination: Comparative Evaluation of the Efficacy and Cross-Protection Capacity of DNA vs. Peptide-Based Vaccines in a Murine Model

A Tailored Approach to Leishmaniases Vaccination: Comparative Evaluation of the Efficacy and Cross-Protection Capacity of DNA vs. Peptide-Based Vaccines in a Murine Model

Leishmania Vaccines: the Current Situation with Its Promising Aspect for the Future

Memory T cells: promising biomarkers for evaluating protection and vaccine efficacy against leishmaniasis

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