Virus-like particle vaccine elicits cross-protection against L. donovani in mice

A virus-like particle vaccine carrying a surface antigen from the parasite Leishmania amazonensis drastically reduced parasite burden in the visceral organs of mice challenged with a different species, L. donovani, according to a study published in Parasites & Vectors. The work addresses a persistent gap in leishmaniasis vaccine research: most candidate vaccines based on promastigote surface antigen, or PSA, have been tested only against the same parasite species used to make the vaccine, leaving cross-species protection largely unexplored. The researchers built their vaccine platform on influenza virus-like particles expressing the PSA of L. amazonensis, which self-assembled in Spodoptera frugiperda insect cells.

The team characterized the particles by SDS-PAGE, western blotting and transmission electron microscopy to confirm successful assembly and antigen expression. L. amazonensis parasites engineered to express mCherry fluorescence were cultured, and a peak growth time point was selected for the work. A key rationale for the approach came from sequence analysis.

The nucleotide and amino acid sequences of PSA from L. amazonensis and L. donovani were found to be highly similar, signifying that cross-reactivity between the two species can occur. This shared similarity underpinned the hypothesis that an immune response raised against one species' antigen might recognize the other. To evaluate heterologous protection, mice were immunized three times at three-week intervals by the intramuscular route, with blood collected one week after each immunization.

Three weeks after the final dose, the animals were challenge-infected and killed two weeks post-infection for sample collection. The researchers then assessed antibody responses, immune cell populations, cytokine production and parasite burden. The results showed that LaPSA-VLP immunization elicited cross-reactive IgG antibodies that reacted with L. donovani antigens, not only those of the species from which the antigen was derived.

Compared with unimmunized controls, vaccinated animals developed germinal center B cells and both CD4-positive and CD8-positive T cells, pointing to engagement of adaptive immune pathways relevant to parasite clearance. Inflammation in the liver was also significantly reduced in vaccinated mice, which the authors attributed to limited production of the cytokines IFN-γ and IL-6. The most striking outcome, however, was the drastic reduction in parasite burden in the visceral organs, which the authors interpret as evidence that the PSA antigen derived from L. amazonensis can confer cross-protection against L. donovani infection in this model.

The article is published open access as an early-release, peer-reviewed accepted manuscript carrying a permanent DOI, citable ahead of the final version of record, which will replace it after further edits. The study's findings are limited to the mouse model and the two-week post-challenge observation window reported, and clinical relevance in humans remains to be established.

Subject of Research: Leishmania amazonensis promastigote surface antigen expressed on virus-like particles elicits cross-protective immunity against L. donovani in mice

Article Title: Leishmania amazonensis promastigote surface antigen expressed on virus-like particles elicits cross-protective immunity against L. donovani in mice

Article References: Heo, S. I., Eom, G.-D., Yoon, K.-W., Mao, J., Nam, H.-W., Lee, J.-H., Kang, H.-J., Chu, K. B., Bae, H., Lee, Y. S., Singh, M. K., Kim, S. S., & Quan, F.-S. (2026). Leishmania amazonensis promastigote surface antigen expressed on virus-like particles elicits cross-protective immunity against L. donovani in mice. Parasites & Vectors. https://doi.org/10.1186/s13071-026-07738-x

Image Credits: AI Generated

DOI: 10.1186/s13071-026-07738-x

Keywords: Leishmania, amazonensis, promastigote, surface, antigen, expressed, virus-like, particles, elicits, cross-protective, immunity, against