Protective Humoral Immune Response Induced by Recombinant Virus-like Particle Vaccine Expressing Leishmania donovani Surface Antigen

ACS Infect Dis. 2023 Dec 8;9(12):2583-2592. doi: 10.1021/acsinfecdis.3c00411. Epub 2023 Nov 28.

Abstract

To date, Leishmania spp. vaccine studies have mainly focused on cellular immunity induction, which plays a crucial role in host protection. In contrast, vaccine-induced humoral immunity is largely neglected. Virus-like particle (VLP) vaccines generated using the baculovirus expression system are well-known inducers of humoral immunity and would serve as a suitable platform for evaluating humoral immunity-mediated protection against visceral Leishmaniasis. In this study, we investigated the humoral immunity evoked through VLPs expressing the L. donovani promastigote surface antigen (PSA-VLPs) and assessed their contribution to protection in mice. PSA-VLPs vaccines were generated using the baculovirus expression system and used for mouse immunizations. Mice were intramuscularly immunized twice with PSA-VLPs and challenged with L. donovani to confirm vaccine-induced protective immunity. PSA-VLP immunization elicited parasite-specific antibody responses in the sera of mice, which were induced in a dose-dependent manner. B cell, germinal center B cell, and memory B cell responses in the spleen were found to be higher in vaccinated mice compared to unimmunized controls. PSA-VLP immunization diminished the production of pro-inflammatory cytokines IFN-γ and IL-6 in the liver. Overall, the PSA-VLPs conferred protection against L. donovani challenge infection by reducing the total parasite burden within the internal organs. These results suggest that PSA-VLPs induced protective immunity against the L. donovani challenge infection.

Keywords: Leishmania donovani; humoral immunity; promastigote surface antigen; protection; virus-like particle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Protozoan / genetics
  • Antigens, Surface
  • Humans
  • Immunity, Humoral
  • Leishmania donovani*
  • Leishmaniasis Vaccines*
  • Male
  • Mice
  • Prostate-Specific Antigen
  • Vaccines, Virus-Like Particle*

Substances

  • Vaccines, Virus-Like Particle
  • Prostate-Specific Antigen
  • Antigens, Protozoan
  • Leishmaniasis Vaccines
  • Antigens, Surface