A chimeric vaccine combined with adjuvant system induces immunogenicity and protection against visceral leishmaniasis in BALB/c mice

In Brazil, canine visceral leishmaniasis is an important public health problem due to its alarming growth. The high prevalence of infected dogs reinforces the need for a vaccine for use in prophylactic vaccination campaigns. In the present study, we evaluate the immunogenicity and protection of the...

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Bibliographic Details
Published in:Vaccine 2021-05, Vol.39 (20), p.2755-2763
Main Authors: Ostolin, Thais Lopes Valentim Di Paschoale, Gusmão, Miriã Rodrigues, Mathias, Fernando Augusto Siqueira, Cardoso, Jamille Mirelle de Oliveira, Roatt, Bruno Mendes, Aguiar-Soares, Rodrigo Dian de Oliveira, Ruiz, Jeronimo Conceição, Resende, Daniela de Melo, de Brito, Rory Cristiane Fortes, Reis, Alexandre Barbosa
Format: Article
Language:English
Subjects:
Adjuvants
Adjuvants, Immunologic
Animals
Antigens
Antigens, Protozoan
BALB/c
Brazil
Cell culture
Cell growth
Cell proliferation
Chimera
Cloning
Combined vaccines
Cytokines
Data analysis
Dogs
Epitopes
Evaluation
Flow cytometry
Immune response
Immunogenicity
Interleukin 10
Interleukin 2
Interleukin 4
Leishmania infantum
Leishmaniasis Vaccines
Leishmaniasis, Visceral - prevention & control
Lipid A
Lipids
Lymphocytes
Lymphocytes T
Mice
Mice, Inbred BALB C
Monophosphoryl lipid A
Multi-epitope vaccine
Nitric oxide
Parasites
Parasitic diseases
Peptides
Promastigotes
Proteins
Public health
Saponins
Spleen
Tumor necrosis factor-α
Vaccination
Vaccine efficacy
Vaccines
Vector-borne diseases
Visceral leishmaniasis
γ-Interferon
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Summary:In Brazil, canine visceral leishmaniasis is an important public health problem due to its alarming growth. The high prevalence of infected dogs reinforces the need for a vaccine for use in prophylactic vaccination campaigns. In the present study, we evaluate the immunogenicity and protection of the best dose of Chimera A selected through the screening of cytokines production important in disease. BALB/c mice were vaccinated subcutaneously with three doses and challenged intravenously with 1 × 107L. infantum promastigotes. Spleen samples were collected to assess the intracellular cytokine profile production, T cell proliferation and parasite load. At first, three different doses of Chimera A (5 μg, 10 μg and 20 μg) were evaluated through the production of IFN-γ and IL-10 cytokines. Since the dose of 20 μg showed the best results, it was chosen to continue the study. Secondarily, Chimera A at dose of 20 μg was formulated with Saponin plus Monophosphoryl lipid A. Vaccination with Chimera A alone and formulated with SM adjuvant system was able to increase the percentage of the proliferation of specific T lymphocytes and stimulated a Th1 response with increased levels of IFN-γ, TNF-α and IL-2, and decreased of IL-4 and IL-10. The vaccine efficacy through real-time PCR demonstrated a reduction in the splenic parasite load in animals that received Chimera A formulated with the SM adjuvant system (92%). Additionally, we observed increased levels of nitric oxide in stimulated-culture supernatants. The Chimera A formulated with the SM adjuvant system was potentially immunogenic, being able to induce immunoprotective mechanisms and reduce parasite load. Therefore, the use of T-cell multi-epitope vaccine is promising against visceral leishmaniasis.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2021.04.004