Identification of Immunodominant Proteins of the Leishmania (Viannia) naiffi SubProteome as Pan-Specific Vaccine Targets against Leishmaniasis

Author:

Jesus-Oliveira Prisciliana1,Silva-Couto Luzinei1,Pinho Nathalia23ORCID,Da Silva-Ferreira André Teixeira4ORCID,Saboia-Vahia Leonardo5,Cuervo Patricia23ORCID,Da-Cruz Alda Maria1678ORCID,Gomes-Silva Adriano19ORCID,Pinto Eduardo Fonseca16

Affiliation:

1. Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil

2. Laboratório de Pesquisa em Leishmanioses, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil

3. Rede de Pesquisas de Neuroinflamação do Rio de Janeiro, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil

4. Laboratorio of Toxinologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil

5. Laboratório de Vírus Respiratórios e Sarampo, Laboratório de Referência para COVID-19 (World Health Organization), Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil

6. Rede de Pesquisas em Saúde, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Rio de Janeiro 20020-000, Brazil

7. Disciplina de Parasitologia, Departamento de Microbiologia, Imunologia e Parasitologia, Faculdade de Ciências Médicas, Universidade Estadual do Rio de Janeiro, Rio de Janeiro 20550-170, Brazil

8. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação (INCT-NIM), Rio de Janeiro 21040-900, Brazil

9. Laboratório de Pesquisa Clínica em Micobacterioses, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil

Abstract

Leishmaniasis is a wide-spectrum disease caused by parasites from Leishmania genus. A well-modulated immune response that is established after the long-lasting clinical cure of leishmaniasis can represent a standard requirement for a vaccine. Previous studies demonstrated that Leishmania (Viannia) naiffi causes benign disease and its antigens induce well-modulated immune responses in vitro. In this work we aimed to identify the immunodominant proteins present in the soluble extract of L. naiffi (sLnAg) as candidates for composing a pan-specific anti-leishmaniasis vaccine. After immunoblotting using cured patients of cutaneous leishmaniasis sera and proteomics approaches, we identified a group of antigenic proteins from the sLnAg. In silico analyses allowed us to select mildly similar proteins to the host; in addition, we evaluated the binding potential and degree of promiscuity of the protein epitopes to HLA molecules and to B-cell receptors. We selected 24 immunodominant proteins from a sub-proteome with 328 proteins. Homology analysis allowed the identification of 13 proteins with the most orthologues among seven Leishmania species. This work demonstrated the potential of these proteins as promising vaccine targets capable of inducing humoral and cellular pan-specific immune responses in humans, which may in the future contribute to the control of leishmaniasis.

Funder

Fundação Oswaldo Cruz

CAPES

CNPq, Conselho Nacional De Desenvolvimento Científico E Tecnológico—Brazil

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro—FAPERJ

Fiocruz’s Technological Platforms Network

Publisher

MDPI AG

Subject

Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology

Reference81 articles.

1. World Health Organization (2022). Global leishmaniasis surveillance: 2021, assessing the impact of the COVID-19 pandemic. Wkly. Epidemiol., 97, 575–590. Available online: https://www.who.int/publications/i/item/who-wer9745-575-590.

2. World Health Organization (2023, February 18). Leishmaniasis. Available online: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis.

3. Leishmania vaccines entered in clinical trials: A review of literature;Rezvan;Int. J. Prev. Med.,2019

4. Modern Subunit Vaccines: Development, Components, and Research Opportunities;Moyle;Chemmedchem,2013

5. Peptide Vaccines for Leishmaniasis;Cardoso;Front. Immunol.,2018

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