Not All Antigens Are Created Equally: Progress, Challenges, and Lessons Associated with Developing a Vaccine for Leishmaniasis

Duthie, Malcolm S.; Reed, Steven G.

doi:10.1128/cvi.00108-17

Cited by 19 publications

(16 citation statements)

References 62 publications

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“…Therefore, the development of a single vaccine capable of inducing cross-protection against the different species of the protozoan would be particularly useful in regions where several Leishmania species coexist. During the last few years, while a great number of antigens have been examined as vaccine candidates across various Leishmania species, only a small number have advanced to human or canine clinical trials [45]. In this context, we have previously demonstrated the features of the HisAK70 DNA vaccine against different forms of leishmaniosis caused by Old World species in the murine model.…”

Section: Discussionmentioning

confidence: 99%

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

et al. 2019

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Leishmania amazonensis is the aetiological agent of a broad spectrum of leishmaniosis in South America. It can cause not only numerous cases of cutaneous leishmaniosis but also diffuse cutaneous leishmaniosis. Considering the diversity of parasite species causing different forms of the disease that coexist in the same region, it is desirable to develop a vaccine capable of eliciting cross-protection. We have previously described the use of HisAK70 DNA vaccine for immunization of mice to assess the induction of a resistant phenotype against Leishmania major and infantum infections. In this study, we extended its application in the murine model of infection by using L. amazonensis promastigotes. Our data revealed that 14 weeks post-infection, HisAK70-vaccinated mice showed key biomarkers of protection, such as higher iNOS/arginase activity, IFN-γ/IL-10, IFN-γ/IL-4, and GM-CSF/IL-10 ratios, in addition to an IgG2a-type response when compared to the control group. These findings correlated with the presentation of lower footpad swelling and parasite burdens in the immunized compared to the control mice. Overall, this study suggests that immunization with HisAK70 may be considered a suitable tool to combat leishmaniosis as it is able to induce a potent cellular immune response, which allows to control the infection caused by L. amazonensis.

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Section: Discussionmentioning

confidence: 99%

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

et al. 2019

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“…While the use of ex vivo conditioned DC-based vaccines has significant practical limitations in the field ( 81 ), some have postulated that the protection mediated by ex vivo pulsed DC vaccination is actually mediated by recipient, not donor DCs. Schnitzer et al demonstrated that fragments of antigen-loaded DCs and even DC-derived exosomes induce protection against L. major needle challenge 1 week following vaccination of BALB/c mice.…”

Section: The Potential Of Dc-based Vaccination Strategies To Address mentioning

confidence: 99%

Translating Observations From Leishmanization Into Non-Living Vaccines: The Potential of Dendritic Cell-Based Vaccination Strategies Against Leishmania

2018

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Leishmaniasis is a health-threatening vector-borne disease in almost 90 different countries. While a prophylactic human vaccine is not yet available, the fact that recovery from leishmaniasis establishes lifelong immunity against secondary infection suggests that a vaccine is attainable. In the past, deliberate infection with virulent parasites, termed Leishmanization, was used as a live-vaccine against cutaneous leishmaniasis and effectively protected against vector-transmitted disease in endemic areas. However, the practice was discontinued due to major complications including non-healing skin lesions, exacerbation of skin diseases, and the potential impact of immunosuppression. Instead, tremendous effort has been made to develop killed, live attenuated, and non-living subunit formulations. Many of these formulations produce promising experimental results but have failed in field trials or against experimental challenge with infected sand flies. Recently, experimental models of leishmanization have unraveled the critical role of parasite persistence in maintaining the circulating CD4+ effector T cells responsible for mitigating the inflammatory response early after sand fly challenge and mediating protective immunity. Here, we put forward the notion that for effective vaccine design (especially non-living vaccines), the role of antigen persistence and pre-existing effector CD4+ T cells should be taken into consideration. We propose that dendritic cell-based vaccination strategies warrant greater attention because of their potential to act as long-term antigen depots, thereby emulating this critical requirement of naturally acquired protective immunity against infected sand fly challenge.

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“…The increasing incidence of zoonotic VL and other forms of the disease necessitates the development of new control strategies, such as prophylactic or immunomodulatory vaccines. During the last few years, while a considerable number of components have been examined as vaccine candidates across various Leishmania species, only a small number have progressed to human or canine clinical trials [ 50 ]. A great number of peptide-based vaccines have been tested using individual antigens or a combination of several peptides that are designed as recombinant products by molecular biology [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Epitope Selection for Fighting Visceral Leishmaniosis: Not All Peptides Function the Same Way

et al. 2020

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Visceral leishmaniosis (VL) caused by Leishmania infantum is a disease with an increasing prevalence worldwide. Treatments are expensive, toxic, and ineffective. Therefore, vaccination seems to be a promising approach to control VL. Peptide-based vaccination is a useful method due to its stability, absence of local side effects, and ease of scaling up. In this context, bioinformatics seems to facilitate the use of peptides, as this analysis can predict high binding affinity epitopes to MHC class I and II molecules of different species. We have recently reported the use of HisAK70 DNA immunization in mice to induce a resistant phenotype against L. major, L. infantum, and L. amazonensis infections. In the present study, we used bioinformatics tools to select promising multiepitope peptides (HisDTC and AK) from the polyprotein encoded in the HisAK70 DNA to evaluate their immunogenicity in the murine model of VL by L. infantum. Our results revealed that both multiepitope peptides were able to induce the control of VL in mice. Furthermore, HisDTC was able to induce a better cell-mediated immune response in terms of reduced parasite burden, protective cytokine profile, leishmanicidal enzyme modulation, and specific IgG2a isotype production in immunized mice, before and after infectious challenge. Overall, this study indicates that the HisDTC chimera may be considered a satisfactory tool to control VL because it is able to activate a potent CD4+ and CD8+ T-cell protective immune responses.

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Not All Antigens Are Created Equally: Progress, Challenges, and Lessons Associated with Developing a Vaccine for Leishmaniasis

Cited by 19 publications

References 62 publications

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

Translating Observations From Leishmanization Into Non-Living Vaccines: The Potential of Dendritic Cell-Based Vaccination Strategies Against Leishmania

Epitope Selection for Fighting Visceral Leishmaniosis: Not All Peptides Function the Same Way

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