A squalene oil emulsified MPL-A and anti-CD200/CD300a antibodies adjuvanted whole-killed Leishmania vaccine provides durable immunity against L. donovani parasites

Antigenic inefficacy to induce robust immune responses and durable memory are major causes of constantly failing prophylactic approaches in leishmaniasis. Here, we determine the potential of a standardized whole-killed Leishmania vaccine (Leishvacc) adjuvanted with anti-CD200 and anti-CD300a antibodies, either alone or with monophosphoryl lipid A (MPL-SE) emulsified in squalene oil, in restoring the compromised antigen presenting abilities of dendritic cells (DCs), effector properties of CD4⁺T cells and providing protection against Leishmania donovani parasites. In animals vaccinated with antibodies adjuvanted vaccines, either alone or with MPL-SE, the antigen presenting abilities of CD11c⁺ DCs against Leishmania antigens, measured in terms of CD80, CD86, MHC-I, and MHC-II surface receptors and intracellular IL-12 were found enhanced than non-adjuvanted vaccine. We observed more proliferative and pro-inflammatory cytokines i.e. IL-2, IFN-γ, IL-23, and IL-12 producing CD4⁺T cells in antibodies/MPL-SE adjuvanted vaccinated animals further suggesting that this approach helps antigen activated CD4⁺T cells to acquire pro-inflammatory cytokines producing abilities. In antibodies, either alone or with MPL-SE, vaccinated animals, the number of CD4⁺ central memory T cells and their longevity were found significantly enhanced that further evidenced the impact of this vaccination approach in inducing long term protective immunity. The animals, receiving antibodies adjuvanted vaccines, either alone or with MPL-SE, exhibited excellent protection against virulent parasites by restricting their growth, which correlated with the significantly reduced parasitemia, splenomegaly, and hepatomegaly, along with fewer numbers of liver granulomas. Our findings provide an insight to a new immunoprophylactic approach against visceral leishmaniasis, which not only satisfies the safety criteria, but also provides a robust immunogenic response with remarkable potential for parasites control. However, further in-depth investigations are needed to ascertain its ability in inducing long-lasting immunity.