Chimeric Vaccines Designed by Immunoinformatics-Activated Polyfunctional and Memory T Cells That Trigger Protection against Experimental Visceral Leishmaniasis

Rory Cristiane Fortes De Brito; Jeronimo Conceição Ruiz; Jamille Mirelle de Oliveira Cardoso; Thais Lopes Valentim Di Paschoale Ostolin; Levi Eduardo Soares Reis; Fernando Augusto Siqueira Mathias; Rodrigo Dian de Oliveira Aguiar-Soares; Bruno Mendes Roatt; Rodrigo Corrêa-Oliveira; Daniela de Melo Resende; Alexandre Barbosa Reis

doi:10.3390/vaccines8020252

Chimeric Vaccines Designed by Immunoinformatics-Activated Polyfunctional and Memory T Cells That Trigger Protection against Experimental Visceral Leishmaniasis

Vaccines (Basel). 2020 May 27;8(2):252. doi: 10.3390/vaccines8020252.

Authors

Rory Cristiane Fortes De Brito¹, Jeronimo Conceição Ruiz^{2

3}, Jamille Mirelle de Oliveira Cardoso¹, Thais Lopes Valentim Di Paschoale Ostolin¹, Levi Eduardo Soares Reis¹, Fernando Augusto Siqueira Mathias¹, Rodrigo Dian de Oliveira Aguiar-Soares¹, Bruno Mendes Roatt^{1

4}, Rodrigo Corrêa-Oliveira⁵, Daniela de Melo Resende^{2

3}, Alexandre Barbosa Reis^{1

4}

Affiliations

¹ Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto 35400-000, Brazil.
² Grupo Informática de Biossistemas e Genômica, Instituto René Rachou, Fiocruz Minas, Belo Horizonte 30190-002, Brazil.
³ Programa de Pós-graduação em Biologia Computacional e Sistemas, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil.
⁴ Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Salvador 40110-160, Brazil.
⁵ Laboratório de Imunologia Celular e Molecular, Instituto René Rachou, Fiocruz Minas, Belo Horizonte 30190-002, Brazil.

Abstract

Many vaccine candidates against visceral leishmaniasis (VL) have been proposed; however, to date, none of them have been efficacious for the human or canine disease. On this basis, the design of leishmaniasis vaccines has been constantly changing, and the use of approaches to select specific epitopes seems to be crucial in this scenario. The ability to predict T cell-specific epitopes makes immunoinformatics an even more necessary approach, as in VL an efficient immune response against the parasite is triggered by T lymphocytes in response to Leishmania spp. immunogenic antigens. Moreover, the success of vaccines depends on the capacity to generate long-lasting memory and polyfunctional cells that are able to eliminate the parasite. In this sense, our study used a combination of different approaches to develop potential chimera candidate vaccines against VL. The first point was to identify the most immunogenic epitopes of Leishmania infantum proteins and construct chimeras composed of Major histocompatibility complex (MHC) class I and II epitopes. For this, we used immunoinformatics features. Following this, we validated these chimeras in a murine model in a thorough memory study and multifunctionality of T cells that contribute to a better elucidation of the immunological protective mechanisms of polyepitope vaccines (chimera A and B) using multicolor flow cytometry. Our results showed that in silico-designed chimeras can elicit polyfunctional T cells producing T helper (Th)1 cytokines, a strong immune response against Leishmania antigen, and the generation of central and effector memory T cells in the spleen cells of vaccinated animals that was able to reduce the parasite burden in this organ. These findings contribute two potential candidate vaccines against VL that can be used in further studies, and help in this complex field of vaccine development against this challenging parasite.

Keywords: Leishmania infantum; chimera vaccine; immunoinformatics; memory T cells; polyfunctional T cells; rational design of vaccines; reverse vaccinology.