A Systematic Immuno-Informatic Approach to Design a Multiepitope-Based Vaccine Against Emerging Multiple Drug Resistant Serratia marcescens

Autor(es)

Folhas Damas, Marcelo Silva ; Mazur, Fernando Gabriel ; de Melo Freire, Caio Cesar ; da Cunha, Anderson Ferreira ; Pranchevicius, Maria-Cristina da Silva

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 13, p. 24-pg., 2022-03-14.

Resumo

Serratia marcescens is now an important opportunistic pathogen that can cause serious infections in hospitalized or immunocompromised patients. Here, we used extensive bioinformatic analyses based on reverse vaccinology and subtractive proteomics-based approach to predict potential vaccine candidates against S. marcescens. We analyzed the complete proteome sequence of 49 isolate of Serratia marcescens and identified 5 that were conserved proteins, non-homologous from human and gut flora, extracellular or exported to the outer membrane, and antigenic. The identified proteins were used to select 5 CTL, 12 HTL, and 12 BCL epitopes antigenic, non-allergenic, conserved, hydrophilic, and non-toxic. In addition, HTL epitopes were able to induce interferon-gamma immune response. The selected peptides were used to design 4 multi-epitope vaccines constructs (SMV1, SMV2, SMV3 and SMV4) with immune-modulating adjuvants, PADRE sequence, and linkers. Peptide cleavage analysis showed that antigen vaccines are processed and presented via of MHC class molecule. Several physiochemical and immunological analyses revealed that all multiepitope vaccines were non-allergenic, stable, hydrophilic, and soluble and induced the immunity with high antigenicity. The secondary structure analysis revealed the designed vaccines contain mainly coil structure and alpha helix structures. 3D analyses showed high-quality structure. Molecular docking analyses revealed SMV4 as the best vaccine construct among the four constructed vaccines, demonstrating high affinity with the immune receptor. Molecular dynamics simulation confirmed the low deformability and stability of the vaccine candidate. Discontinuous epitope residues analyses of SMV4 revealed that they are flexible and can interact with antibodies. In silico immune simulation indicated that the designed SMV4 vaccine triggers an effective immune response. In silico codon optimization and cloning in expression vector indicate that SMV4 vaccine can be efficiently expressed in E. coli system. Overall, we showed that SMV4 multi-epitope vaccine successfully elicited antigen-specific humoral and cellular immune responses and may be a potential vaccine candidate against S. marcescens. Further experimental validations could confirm its exact efficacy, the safety and immunogenicity profile. Our findings bring a valuable addition to the development of new strategies to prevent and control the spread of multidrug-resistant Gram-negative bacteria with high clinical relevance. (AU)

• Processo FAPESP: 18/24213-7 - Análise da presença de genes codificantes de resistência antimicrobiana e virulência em Serratia marcescens e identificação de candidatos a vacina contra Serratia marcescens, através de vacinação reversa
• Beneficiário: Marcelo Silva Folhas Damas
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 20/11964-4 - Caracterização molecular e fenotípica de bactérias oportunistas: desenvolvimento de vacinas e drogas terapêuticas utilizando proteômica subtrativa
• Beneficiário: Maria Cristina da Silva Pranchevicius
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/01316-0 - Uma abordagem sistemática de imuno-informática para desenhar uma vacina baseada em multiepítopos contra a Serratia marcescens emergente e resistente a múltiplas drogas
• Beneficiário: Maria Cristina da Silva Pranchevicius
• Modalidade de apoio: Auxílio à Pesquisa - Publicações científicas - Artigo
• Processo FAPESP: 18/20697-0 - Seleção e evolução dirigida de leveduras - Identificação e análise de vias metabólicas importantes para aplicação nas indústrias do bioetanol e de bebidas fermentadas.
• Beneficiário: Anderson Ferreira da Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Regular