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

Autor: Ostolin TLVDP; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Ouro Preto, Brazil., Gusmão MR; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Ouro Preto, Brazil., Mathias FAS; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Ouro Preto, Brazil; Grupo Informática de Biossistemas e Genômica, Instituto René Rachou, Fiocruz Minas, Belo Horizonte, Brazil., Cardoso JMO; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Ouro Preto, Brazil., Roatt BM; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Ouro Preto, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Salvador, Brazil., Aguiar-Soares RDO; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Ouro Preto, Brazil., Ruiz JC; Grupo Informática de Biossistemas e Genômica, Instituto René Rachou, Fiocruz Minas, Belo Horizonte, Brazil., Resende DM; Grupo Informática de Biossistemas e Genômica, Instituto René Rachou, Fiocruz Minas, Belo Horizonte, Brazil., de Brito RCF; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Ouro Preto, Brazil., Reis AB; Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas (NUPEB), Universidade Federal de Ouro Preto, Ouro Preto, Brazil; Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Salvador, Brazil. Electronic address: alexreis@ufop.edu.br.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2021 May 12; Vol. 39 (20), pp. 2755-2763. Date of Electronic Publication: 2021 Apr 17.
DOI: 10.1016/j.vaccine.2021.04.004
Abstrakt: 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 × 10 7 L. 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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