Vaccination with Live Attenuated L. Major and TLR4 Agonist Promotes a Th1 Immune Response and Induces Protection against L. Major Infection in BALB/c Mice

Abstract

<strong>Background:</strong> Toll like receptors play a major role in immune responses against <em>Leishmania </em>parasites. <strong>Objective: </strong>To evaluate the efficacy of vaccination with live attenuated <em>L. major</em> and TLR4 agonist in protection against <em>L. major</em> infection. <strong>Methods:</strong> Attenuated <em>L. major</em> was prepared by continuous sub-culturing of the parasite. A total of 90 mice were assigned to 9 groups including 6 groups of BALB/c (G1-6) and 3 groups (G7-9) of C57BL/6 mice. Group 1 was the control groups, group 2 received the wild-type <em>L. major </em>promastigotes, group 3 the attenuated line, group 4 the TLR4 agonist, group 5 the wild-type <em>L. major</em> and TLR4 agonist, and group 6 the attenuated line along with TLR4 agonist. Group 7 was control, group 8 received wild-type <em>L. major </em>and group 9 the wild-type along with TLR4 agonist. Vaccinated mice were then challenged with wild-type of <em>L. major.</em> Lesion size, parasite burden, and the expression levels of IL-4, IFN-γ, IL-2, 1L-17A, IL-10, TGF-β and TLR4 were evaluated before the challenge while parasite burden and lesion size were evaluated. <strong>Results:</strong> Vaccinated mice with a TLR4 agonist or attenuated <em>L. major</em> plus TLR4 agonist produced the highest levels of IFN-γ, IL-2, and IL-17A. Post-challenge analysis revealed that mice vaccinated with the attenuated line along with TLR4 agonist displayed the lowest lesion size and parasite load. These mice developed a predominant Th1 immune response. <strong>Conclusion:</strong> Vaccination with the attenuated <em>L. major</em> along with TLR4 agonist promotes a Th1-mediated immune response which leads to the protection of BALB/c mice against <em>L. major</em> infection.