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

• 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
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2021.04.004

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.