Intranasal immunization with chitosan microparticles enhances LACK-DNA vaccine protection and induces specific long-lasting immunity against visceral leishmaniasis

Microbes Infect. 2022 Mar;24(2):104884. doi: 10.1016/j.micinf.2021.104884. Epub 2021 Sep 3.

Abstract

Development of a protective vaccine against Leishmania depends on antigen formulation and adjuvants that induce specific immunity and long-lasting immune responses. We previously demonstrated that BALB/c mice intranasally vaccinated with a plasmid DNA encoding the p36/LACK leishmanial antigen (LACK-DNA) develop a protective immunity for up to 3 months after vaccination, which was linked with the systemic expression of vaccine mRNA in peripheral organs. In this study, LACK-DNA vaccine was associated with biocompatible chitosan microparticles cross-linked with glyceraldehyde (CMC) to boost the long-lasting immunity against the late Leishmania infantum challenge. Infection at 7 days, 3 or 6 months after vaccination resulted in significantly lower parasite loads when compared with non-vaccinated controls. Besides, LACK-DNA-chitosan vaccinated mice showed long-time protection observed after the late time point challenge. The achieved protection was correlated with an enhanced spleen cell responsiveness to parasite antigens, marked by increased proliferation and IFN-γ as well as decreased IL-10 production. Moreover, we found diminished systemic levels of TNF-α that was compatible with the better health condition observed in LACK-DNA/CMC vaccinated-infected mice. Together, our data indicate the feasibility of chitosan microparticles as a delivery system tool to extend the protective immunity conferred by LACK-DNA vaccine, which may be explored in vaccine formulations against Leishmania parasite infections.

Keywords: DNA vaccine; Intranasal delivery; LACK; Leishmania infantum; Visceral leishmaniasis.

MeSH terms

  • Animals
  • Antigens, Protozoan
  • Chitosan*
  • Immunity, Cellular
  • Immunization
  • Leishmania infantum* / genetics
  • Leishmaniasis, Visceral*
  • Mice
  • Mice, Inbred BALB C
  • Protozoan Proteins / genetics
  • Vaccination
  • Vaccines, DNA* / genetics

Substances

  • Antigens, Protozoan
  • Protozoan Proteins
  • Vaccines, DNA
  • Chitosan