Influenza Virus-Like Particles Displaying Leishmania donovani Promastigote Surface Antigen Induce Cross-Protective Immunity

Virus-like particles expressing the Promastigote surface antigen (PSA) of Leishmania donovani have shown great potential as a vaccine candidate against L. donovani infection. However, their potential as a cross-protective leishmaniasis vaccine candidate has remained unexplored. In this study, we generated the L. donovani PSA-expressing influenza virus-like particle vaccines and evaluated their cross-protective potential against Leishmania amazonensis infection in mice. Virus-like particles expressing the L. donovani PSA on influenza M1 protein (LdPSA-VLP) were self-assembled in insect cells using the baculovirus expression system. To evaluate the efficacy of our LdPSA-VLP vaccine, mice were subcutaneously immunized and then challenged with virulent L. amazonensis. LdPSA-VLP immunization elicited L. amazonensis antigen-specific IgG antibodies. Upon challenge infection with mCherry-expressing L. amazonensis, L. amazonensis-specific antibody-secreting cell responses, germinal center B cell, memory B cell, and CD4⁺/CD8⁺ T cell responses were markedly enhanced in immunized mice. Footpad inflammation was significantly inhibited, as indicated by decreased proinflammatory cytokine production. LdPSA-VLP provided cross-protection against L. amazonensis by reducing footpad swelling and parasite burden in the footpads. Our findings indicate that LdPSA-VLPs could serve as promising cross-protective vaccine candidates against cutaneous leishmaniasis.