Pam3CSK4 adjuvant given intranasally boosts anti-Leishmania immunogenicity but not protective immune responses conferred by LaAg vaccine against visceral leishmaniasis

Caio Loureiro Salgado, Emmanoel Loss Dias, Lorenzzo Lyrio Stringari, Luciana Polaco Covre, Reynaldo Dietze, Fausto Edmundo Lima Pereira, Herbet Leonel de Matos Guedes, Bartira Rossi-Bergmann, Daniel Claudio Oliveira Gomes

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

The use of adjuvants in vaccine formulations is a well-established practice to improve immunogenicity and protective immunity against diseases. Previously, we have demonstrated the feasibility of intranasal vaccination with the antigen of killed Leishmania amazonensis promastigotes (LaAg) against experimental leishmaniasis. In this work, we sought to optimize the immunogenic effect and protective immunity against murine visceral leishmaniasis conferred by intranasal delivery of LaAg in combination with a synthetic TLR1/TLR2 agonist (Pam3CSK4). Intranasal vaccination with LaAg/PAM did not show toxicity or adverse effects, induced the increase of delayed-type hypersensitivity response and the production of inflammatory cytokines after parasite antigen recall. However, mice vaccinated with LaAg/PAM and challenged with Leishmania infantum presented significant reduction of parasite burden in both liver and spleen, similar to those vaccinated with LaAg. Although LaAg/PAM intranasal vaccination had induced higher frequencies of specific CD4+ and CD8+ T cells and increased levels of IgG2a antibody isotype in serum, both LaAg and LaAg/PAM groups presented similar levels of IL-4 and IFN-y and decreased production of IL-10 when compared to controls. Our results provide the first evidence of the feasibility of intranasal immunization with antigens of killed Leishmania in association with a TLR agonist, which may be explored for developing an effective and alternative strategy for vaccination against visceral leishmaniasis.

Original languageEnglish
Pages (from-to)328-335
Number of pages8
JournalMicrobes And Infection
Volume21
Issue number7
DOIs
Publication statusPublished - 1 Aug 2019

Keywords

  • Intranasal vaccination
  • LaAg
  • Leishmania infantum
  • Pam3CSK4 adjuvant
  • TLR1/TLR2 agonist

UN Sustainable Development Goals (SDGs)

  • SDG 3 - Good Health and Well-Being

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