Adjuvantation of whole-killed Leishmania vaccine with anti-CD200 and anti-CD300a antibodies potentiates its efficacy and provides strong protection against virulent parasites

Abstract

The poor abilities of parasitic antigens to induce cell-mediated immunity is one of the major reasons for the limited success of vaccine candidates against all forms of leishmaniasis. Here we find, for the first time, that the adjuvantation of whole-killed Leishmania vaccine with anti-CD200 and anti-CD300a antibodies significantly enhances CD4+ T cells mediated immunity in vaccinated animals and provides strong protection against virulent parasites. The antibody adjuvantation, either alone or with a TLR4 agonist monophosphoryl A (MPL-A), significantly induced the production of pro-inflammatory cytokines viz., IFN-γ, TNF-α, IL-12, and IL-2 by antigen experienced CD4+ T cells, and also enhanced their rate of conversion into their memory phenotypes. The antibody adjuvantation also promoted the establishment of IgG2a-mediated protective humoral immunity against parasitic antigens. The vaccinated animals showed strong resilience against virulent L. donovani parasites as we observed reduced clinical features such as splenomegaly, hepatomegaly, granulomatous tissues in the liver, and significantly less parasitic load in their spleen. The findings of this study demonstrate that the anti-CD200 and anti-CD300a antibodies adjuvantation significantly increases the protective efficacy of the whole-killed Leishmania vaccine. This study opens up a new gateway to diversify the roles of immune inhibitory molecules in vaccine development against leishmaniasis.