Abstract
Leishmaniasis is a neglected protozoan parasitic disease that occurs in 88 countries but a vaccine is unavailable. Vaccination with live, killed, attenuated (physically or genetically) Leishmania have met with limited success, while peptide-, protein-, or DNA-based vaccines showed promise only in animal models. Here, we critically assess several technical issues in vaccination and expectation of a host-protective immune response. Several studies showed that antigen presentation during priming and triggering of the same cells in infected condition are not comparable. Altered proteolytic processing, antigen presentation, protease-susceptible sites, and intracellular expression of pathogenic proteins during Leishmania infection may vary dominant epitope selection, MHC-II/peptide affinity, and may deter the reactivation of desired antigen-specific T cells generated during priming. The robustness of the memory T cells and their functions remains a concern. Presentation of the antigens by Leishmania-infected macrophages to antigen-specific memory T cells may lead to change in the T cells’ functional phenotype or anergy or apoptosis. Although cells may be activated, the peptides generated during infection may be different and cross-reactive to the priming peptides. Such altered peptide ligands may lead to suppression of otherwise active antigen-specific T cells. We critically assess these different immunological issues that led to the non-availability of a vaccine for human use.
Highlights
The earliest vaccination protocols by Edward Jenner, Louis Pasteur, and Robert Koch demonstrated that killed, live-attenuated, or xenogenic microorganisms induced host-protective immunity [1]
Phagosomal maturation is a step, which Leishmania targets initially to survive inside macrophages until the time it transforms into acid-resistant amastigote form, inhibiting survive inside macrophages until the time it transforms into acid-resistant amastigote form, the antigen presentation process and affecting the vaccine-primed antigen-specific T cells’ reactivation inhibiting the antigen presentation process and affecting the vaccine-primed antigen-specific T cells’
CD40 and CD80 play a crucial role in anti-Leishmania T-cell activation, wherein L. major-infected macrophages co-cultured with peripheral blood leukocytes (PBL) showed an IFN–γ- and CD40-mediated increase in the expression of CD40 and
Summary
The earliest vaccination protocols by Edward Jenner, Louis Pasteur, and Robert Koch demonstrated that killed, live-attenuated, or xenogenic microorganisms induced host-protective immunity [1]. During the hundred years, the modus operandi of the immune system and the vaccine-induced protective immunity has been gradually deciphered and the central dogma of vaccination has been framed. It holds that an immunogen is capable of inducing long-lived immunological memory and protective immunity against rechallenge with the same pathogen [2]. This concept has been successful in generating potent vaccines for many deadly diseases, leishmaniasis caused by the protozoan parasite. In in the case of Leishmania, all the protocols have failed so far in protecting human vaccines
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