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

Toll like receptors play a major role in immune responses against Leishmania parasites. To evaluate the efficacy of vaccination with live attenuated L. major and TLR4 agonist in protection against L. major infection. Attenuated L. major 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 L. major promastigotes, group 3 the attenuated line, group 4 the TLR4 agonist, group 5 the wild-type L. major and TLR4 agonist, and group 6 the attenuated line along with TLR4 agonist. Group 7 was control, group 8 received wild-type L. major and group 9 the wild-type along with TLR4 agonist. Vaccinated mice were then challenged with wild-type of L. major. 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. Vaccinated mice with a TLR4 agonist or attenuated L. major 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. Vaccination with the attenuated L. major along with TLR4 agonist promotes a Th1-mediated immune response which leads to the protection of BALB/c mice against L. major infection.