Special Issue "Vaccines for Leishmaniasis and the Implications of Their Development"

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against (re)emerging and Tropical Infections Diseases".

Deadline for manuscript submissions: 31 December 2022 | Viewed by 3098

Special Issue Editors

Dr. Pedro José Alcolea
E-Mail Website
Guest Editor
Department of Molecular Microbiology and Biology of Infections and Service of Proteomics and Genomics, Centro de Investigaciones Biológicas (Consejo Superior de Investigaciones Científicas), Madrid, Spain
Interests: Leishmania genomics; vaccines; protein structure and function
Dr. Ana M. Alonso
E-Mail Website
Co-Guest Editor
Institution of Gender and Women's Studies, CSIC—Centro de Investigaciones Biologicas (CIB), Madrid, Spain
Interests: leishmaniasis

Special Issue Information

Dear Colleagues,

A few efficacious vaccines against canine leishmaniasis are available, though high protection efficiency is desirable. The search for effective vaccines against pathogens is never easy, and it is especially challenging concerning parasites. Unambiguous determination of the protection of an animals or patients against the parasite requires a better understanding of the immune response to Leishmania spp. Currently, parasite burden determination and clinical sign assessment are the only pivotal parameters for this purpose. Strictly speaking, the Th polarization paradigm is valid for the Leishmania major—mouse infection model, whereas canine and human leishmaniases are characterized by a balanced immune response. Increased parasite burden; Th2 response predominance; IL-10 and TGF-β expression; Leishmania-specific cell immunosuppression; and Leishmania-specific IgG, IgM, IgA and IgE are associated with disease progression. Conversely, increased PBMC levels after leishmanial antigen stimulation, IFN-γ and TNF-α expression, T CD4+, CD8+ and B cell proliferation, and positive IDR are related to the achievement of protection against the parasite. The role of antigen-presenting cells is pivotal in a successful immune response against Leishmania, stimulating IL-1, IL-6, and IL-12 production. IL-12 triggers the differentiation of immature T cells into Th1 and Th17. Th17 cells may favor protection against human VL via IFN-γ and IL-17 production but may lead to disease progression in the case of human CL. IFN-γ and IgG2a associations with protection and fluctuations over time depending on the host species are debatable. iNOS induction and subsequent NO production associated with the Th1 response is the most remarkable protection mechanism, but certain parasite strains are resistant to NO. A better understanding of the Leishmania evasion mechanisms is still required, including inhibition of NO production, ROS-mediated host cell killing, blocking of antigen presentation and cytokine production, and recruitment of cells secreting IL-10 such as T regulatory cells. In addition to this complexity, vaccine experimentation for leishmaniasis is especially challenging because rodents are not always an appropriate animal model, particularly for VL, and the commercial reagents used are usually scarcer and of lower quality. Therefore, I encourage you to contribute to this Special Issue with a vaccine trial report (either positive or negative), a vaccine trial review, or a specific industrial development or methods paper, to move vaccine research forward. Immune response research papers and reviews are also welcome, particularly those that organize knowledge and improve our understanding of the immune response and parasite evasion mechanisms.

Dr. Pedro José Alcolea
Dr. Ana Alonso
Guest Editors

Manuscript Submission Information

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Keywords

  • Leishmania
  • Vaccines, immune response assessment
  • Antigen presentation, lymphoblastic proliferation
  • Cytokines, evasion mechanisms
  • Nitric oxide resistance
  • Antigens, vaccine candidates, and adjuvants
  • Parasite burden
  • Clinical signs, diagnosis
  • Immunoinformatics, genomics
  • Therapeutic vaccines, industrial development.

Published Papers (3 papers)

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Research

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Article
Leishmania infantum UBC1 in Metacyclic Promastigotes from Phlebotomus perniciosus, a Vaccine Candidate for Zoonotic Visceral Leishmaniasis
Vaccines 2022, 10(2), 231; https://doi.org/10.3390/vaccines10020231 - 03 Feb 2022
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Abstract
Leishmania parasites cause outstanding levels of morbidity and mortality in many developing countries in tropical and subtropical regions. Numerous gene expression profiling studies have been performed comparing different Leishmania species’ life-cycles and stage forms in regard to their distinct infective ability. Based on [...] Read more.
Leishmania parasites cause outstanding levels of morbidity and mortality in many developing countries in tropical and subtropical regions. Numerous gene expression profiling studies have been performed comparing different Leishmania species’ life-cycles and stage forms in regard to their distinct infective ability. Based on expression patterns, homology to human orthologues, in silico HLA-binding predictions, and annotated functions, we were able to select several vaccine candidates which are currently under study. One of these candidates is the Leishmania infantum ubiquitin-conjugating enzyme E2 (LiUBC1), whose relative levels, subcellular location, in vitro infectivity in the U937 myeloid human cell model, and protection levels in Syrian hamsters against L. infantum infection were studied herein. LiUBC1 displays a low level of similarity with the mammalian orthologs and relevant structure differences, such as the C-terminal domain, which is absent in the human ortholog. LiUBC1 is present in highly infective promastigotes. Knock-in parasites overexpressing the enzyme increased their infectivity, according to in vitro experiments. Syrian hamsters immunized with the recombinant LiUBC1 protein did not show any parasite burden in the spleen, unlike the infection control group. The IFN-γ transcript levels in splenocytes were significantly higher in the LiUBC1 immunized group. Therefore, LiUBC1 induced partial protection against L. infantum in the Syrian hamster model. Full article
(This article belongs to the Special Issue Vaccines for Leishmaniasis and the Implications of Their Development)
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Article
HLA-DRB1 Alleles Associated with Lower Leishmaniasis Susceptibility Share Common Amino Acid Polymorphisms and Epitope Binding Repertoires
Vaccines 2021, 9(3), 270; https://doi.org/10.3390/vaccines9030270 - 17 Mar 2021
Cited by 2 | Viewed by 1540
Abstract
Susceptibility for leishmaniasis is largely dependent on host genetic and immune factors. Despite the previously described association of human leukocyte antigen (HLA) gene cluster variants as genetic susceptibility factors for leishmaniasis, little is known regarding the mechanisms that underpin these associations. To better [...] Read more.
Susceptibility for leishmaniasis is largely dependent on host genetic and immune factors. Despite the previously described association of human leukocyte antigen (HLA) gene cluster variants as genetic susceptibility factors for leishmaniasis, little is known regarding the mechanisms that underpin these associations. To better understand this underlying functionality, we first collected all known leishmaniasis-associated HLA variants in a thorough literature review. Next, we aligned and compared the protection- and risk-associated HLA-DRB1 allele sequences. This identified several amino acid polymorphisms that distinguish protection- from risk-associated HLA-DRB1 alleles. Subsequently, T cell epitope binding predictions were carried out across these alleles to map the impact of these polymorphisms on the epitope binding repertoires. For these predictions, we used epitopes derived from entire proteomes of multiple Leishmania species. Epitopes binding to protection-associated HLA-DRB1 alleles shared common binding core motifs, mapping to the identified HLA-DRB1 amino acid polymorphisms. These results strongly suggest that HLA polymorphism, resulting in differential antigen presentation, affects the association between HLA and leishmaniasis disease development. Finally, we established a valuable open-access resource of putative epitopes. A set of 14 HLA-unrestricted strong-binding epitopes, conserved across species, was prioritized for further epitope discovery in the search for novel subunit-based vaccines. Full article
(This article belongs to the Special Issue Vaccines for Leishmaniasis and the Implications of Their Development)
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Review

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Review
Humoral and Cellular Immune Response in Asymptomatic Dogs with Visceral Leishmaniasis: A Review
Vaccines 2022, 10(6), 947; https://doi.org/10.3390/vaccines10060947 - 14 Jun 2022
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Abstract
Visceral leishmaniasis is one of the deadliest parasitic diseases in the world and affects both humans and dogs. The host immune response to Leishmania infection plays a critical role in the evolution of canine visceral leishmaniasis (CVL) and consequently in the manifestation of [...] Read more.
Visceral leishmaniasis is one of the deadliest parasitic diseases in the world and affects both humans and dogs. The host immune response to Leishmania infection plays a critical role in the evolution of canine visceral leishmaniasis (CVL) and consequently in the manifestation of clinical signs. The asymptomatic form of the disease is a major concern in the diagnosis of CVL and in the transmission control of Leishmania infection. Asymptomatic dogs are found in large proportions in endemic areas and are an unquantifiable source of infection. The present review analyzes the possible relationship between the activation of the antigen-specific immune response of the host and resistance or susceptibility to CVL. The review focuses on works that address the characterization of the humoral and cellular immune response profile, at both the functional and phenotypic levels, in infected dogs. Most studies relate the absence of clinical symptomatology to an increased proliferative response and a Th1 cytokine profile. Despite the numerous findings pointing to a differential immune response in asymptomatic dogs, the contradictory results reported in this review highlight the importance of establishing a precise clinical classification of the disease, performing more longitudinal studies, and including a higher number of animals in trials. Full article
(This article belongs to the Special Issue Vaccines for Leishmaniasis and the Implications of Their Development)
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