Vaccination using live attenuated Leishmania donovani centrin deleted parasites induces protection in dogs against Leishmania infantum

Genetically Modified Live Attenuated Leishmania donovani Parasites Induce Innate Immunity through Classical Activation of Macrophages That Direct the Th1 Response in Mice

“…6G). Thus, these results suggest that live attenuated parasite-infected BMDM are capable of inducing the proliferation of Th1 type CD4 ϩ T cells in vitro, and the findings are consistent with an enhanced adaptive immune response to live attenuated parasites in various animal models as has been demonstrated elsewhere (40)(41)(42)(43).…”

“…Further, in live attenuated parasite-infected mice, the antigen-presenting abilities of macrophages were skewed toward a more effective Th1 response. These studies confirmed that the protective adaptive immune response generated by live attenuated parasites against wild-type L. donovani challenge previously observed by us (40)(41)(42)(43) is directed by the innate response generated by host macrophages.…”

“…The live attenuated vaccines allow the host immune system to interact with a broad repertoire of antigens considered crucial in the development of protective immunity and, notably, cause no pathology (39). Recently, we demonstrated that these genetically modified L. donovani parasites (Ldp27 Ϫ/Ϫ and LdCen Ϫ/Ϫ ) when used as vaccine candidates induced protection against virulent L. donovani infection in various animal models (mice, hamsters, and dogs), as indicated by control of parasitemia and the induction of a host protective T cell response (40)(41)(42)(43). Since macrophage activation plays an important role in the commitment of T cells to either a protective (Th1) or disease-causing (Th2) phenotype during Leishmania infection (44), it is essential to study the role of macrophages and their phenotypes (M1 and M2) in live attenuated parasite-induced immunity.…”

Visceral Leishmaniasis Control and Elimination: Is There a Role for Vaccines in Achieving Regional and Global Goals?

“…27 These vaccines are intended to mimic the natural course of infection to facilitate a strong, long-lasting, and protective immune response. One candidate vaccine currently being evaluated is an attenuated L. donovani parasite LdCen −/− (in which centrin, a Ca 2+ -binding protein critical for cell division is deleted); thus far, it has been shown to have an adequate safety profile and induce immune responses in mice, hamsters, and dogs, 28,29 and to protect against infection from multiple parasite species in animal models. 30 Another approach uses oxidatively photoinactivated, attenuated promastigotes, which were shown to be safe 31 and protective against VL 32 in small animals, and demonstrated promising results as immunotherapy for canine leishmaniasis in an open-label trial in Naples, Italy.…”

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

“…To target and appropriately skew the anti-Leishmania response, vaccines require both pathogen-specific antigens and immune-stimulating molecules to be rendered effective. Whole and genetically attenuated parasites, such as L. donovani centrin-deleted parasites (LdCen1 Ϫ/Ϫ ), have undergone trials in both dogs and humans (4)(5)(6)(7)(8). Dendritic cell (DC)-based vaccines represent a more refined strategy and have been used in preclinical models.…”