CpG-adjuvanted virus-like particle vaccine induces protective immunity against Leishmania donovani infection

J Infect Dis. 2024 Oct 24:jiae526. doi: 10.1093/infdis/jiae526. Online ahead of print.

Abstract

Visceral leishmaniasis (VL) poses a significant public health challenge due to the lack of an approved human vaccine. We attempted to enhance the efficacy of virus-like particle vaccines expressing the Leishmania donovani promastigote surface antigen (LdPSA-VLP) by adjuvanting with CpG oligodeoxynucleotide (CpG-ODN). Here, adjuvanted vaccine-induced immune responses and their efficacies in mice challenged with mCherry-expressing L. donovani promastigotes were evaluated. Adjuvanted LdPSA-VLP vaccination significantly elevated parasite-specific IgG, IgG1, IgG2a, and IgG2b serum antibody levels. Additionally, vaccinated mice exhibited enhanced germinal center B cells and splenic T cell activities, compared to unimmunized mice. Importantly, adjuvanted LdPSA-VLPs reduced the levels of inflammatory cytokines IFN-γ and IL-6 in visceral organs, leading to decreased total parasite burden and protection against L. donovani challenge. Our findings indicate that CpG-ODN enhanced the protection conferred by LdPSA-VLPs, offering a promising step toward effective VL vaccine development.

Keywords: Leishmania donovani; CpG oligodeoxynucleotide; LdPSA; vaccine; virus-like particle.