Vaccination Route That Induces Transforming Growth Factor β Production Fails To Elicit Protective Immunity against<i>Leishmania donovani</i>Infection

Bhowmick, Sudipta; Mazumdar, Tuhina; Ali, Nahid

doi:10.1128/iai.01739-07

Cited by 44 publications

(44 citation statements)

References 39 publications

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“…Liposome vaccine technology has advanced in recent years, and now several vaccines containing liposome-based adjuvants have been approved for human use or have reached late stages of clinical evaluation [61]. In contrast to a report [62] preferring intra-peritoneal route for liposome-encapsulated antigen, our liposomal formulation given through subcutaneous route was effective. Subcutaneous route is always considered as a slow release route in case of antigen presentation, allowing the body to generate enough resources to counter the invading microorganisms.…”

Section: Discussioncontrasting

confidence: 40%

Evaluation of the immunogenicity and protective efficacy of Killed Leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis

Thakur

Kaur

2014

Med Microbiol Immunol

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Visceral leishmaniasis (VL) caused by Leishmania donovani is a life-threatening disease involving uncontrolled parasitization of vital organs. Drugs to treat leishmaniasis have one or more limitations or insufficiencies in the long run. A safe and efficacious vaccine to control this disease is needed. Killed antigens that could be safer as vaccines have shown limited efficacy in clinical trials. Immunogenic enhancement with appropriate adjuvants may thus be required to elicit protective immunity based on antibodies and effector T-cell functions. Therefore, it is essential to search for adjuvant to enhance the immunogenicity of killed vaccines and to induce protection against leishmaniasis. So, the aim of the present study was to compare the effectiveness of four adjuvants, i.e. alum, saponin, monophosphoryl lipid A, cationic liposome in combination with Killed Leishmania donovani (KLD) antigen against murine VL. Animals were immunized subcutaneously thrice at an interval of 2 weeks with a final volume of 100 μl per dose. Challenge infection was given 2 weeks after last booster. Mice were sacrificed 15 days after last immunization and on 30, 60 and 90 post-infection/challenge days. The protective efficacy of vaccines was revealed by significant reduction in parasite burden and enhanced DTH responses in comparison with the infected controls. Immunized animals also generated significant levels of Th1 cytokines and increased production of IgG2a, thus indicating the generation of a protective Th1 response. All the adjuvants imparted significant protection, but liposomal formulation was most effective followed by KLD + MPL-A, KLD + saponin, KLD + alum and KLD antigen.

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Section: Discussioncontrasting

confidence: 40%

Evaluation of the immunogenicity and protective efficacy of Killed Leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis

Thakur

Kaur

2014

Med Microbiol Immunol

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“…While it is agreed that the route of immunization of protein antigens may also influence the development of an immune response, the effects of various routes on the level and type of immune responses generated and their subsequent impact on challenge infections have remained largely unknown [8]. The effect of route of injection on the immune response has been reported for immunization by particulate antigens [15,16].…”

Section: Discussionmentioning

confidence: 99%

“…More specifically, the route of infection has been reported to be an important variable in different experimental models for Leishmania parasites [6-8]. It was also reported that the route of infection with live Leishmania major vaccine has a critical role in the efficacy of vaccination [9].…”

Section: Introductionmentioning

confidence: 99%

The Route of Leishmania tropica Infection Determines Disease Outcome and Protection against Leishmania major in BALB/c Mice

et al. 2013

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Leishmania tropica is one of the causative agents of leishmaniasis in humans. Routes of infection have been reported to be an important variable for some species of Leishmania parasites. The role of this variable is not clear for L. tropica infection. The aim of this study was to explore the effects of route of L. tropica infection on the disease outcome and immunologic parameters in BALB/c mice. Two routes were used; subcutaneous in the footpad and intradermal in the ear. Mice were challenged by Leishmani major, after establishment of the L. tropica infection, to evaluate the level of protective immunity. Immune responses were assayed at week 1 and week 4 after challenge. The subcutaneous route in the footpad in comparison to the intradermal route in the ear induced significantly more protective immunity against L. major challenge, including higher delayed-type hypersensitivity responses, more rapid lesion resolution, lower parasite loads, and lower levels of IL-10. Our data showed that the route of infection in BALB/c model of L. tropica infection is an important variable and should be considered in developing an appropriate experimental model for L. tropica infections.

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“…These differences have been attributed to differences in the abilities of diverse antigen-presenting cells at different sites to process and present peptides from the HEL protein (43). It has been suggested that enhanced T cell priming by skin-resident DCs and Langerhans cells is the reason why intradermal vaccine inoculation is often superior to intramuscular inoculation (18,19). The influence of the inoculation site on the outcome of L. major infection has been studied largely in the context of site-dependent adaptive immunity, irrespective of dose, and typically with reference to the Th1/Th2 nature of responding CD4 ϩ T cells or the production of the regulatory cytokine IL-10 or transforming growth factor ␤ (TGF-␤) (1, 3-5, 7-9, 41).…”

Section: Discussionmentioning

confidence: 99%

“…Vaccination by different routes has also been shown to influence the efficacy of vaccines against parasitic, bacterial, and viral infections, as well as cancer (3,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). In the case of infections initiated in the skin by the bite of an insect vector, such as Yersinia, Plasmodium, Borrelia, and Leishmania infections (29), the use of an intradermal route of infection would appear to be critical, since the initial interaction between these pathogens and the host takes place primarily in the skin under natural conditions (11,15,(30)(31)(32).…”

mentioning

confidence: 99%

Site-Dependent Recruitment of Inflammatory Cells Determines the Effective Dose of Leishmania major

et al. 2014

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Vaccination Route That Induces Transforming Growth Factor β Production Fails To Elicit Protective Immunity againstLeishmania donovaniInfection

Cited by 44 publications

References 39 publications

Evaluation of the immunogenicity and protective efficacy of Killed Leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis

Evaluation of the immunogenicity and protective efficacy of Killed Leishmania donovani antigen along with different adjuvants against experimental visceral leishmaniasis

The Route of Leishmania tropica Infection Determines Disease Outcome and Protection against Leishmania major in BALB/c Mice

Site-Dependent Recruitment of Inflammatory Cells Determines the Effective Dose of Leishmania major

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