Evaluation of tetravalent and conserved synthetic peptides vaccines derived from Dengue virus Envelope domain I and II.
Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing a secondary infection with a different serotype progress to the severe form of the disease, called dengue hemorrhagic fever. In this study, the vaccine potential of three tetravalent and conserved synthetic peptides derived from DENV envelope domain I (named Pep01) and II (named Pep02 and Pep03) was evaluated. Human dengue IgM/IgG positive serum (n=16) showed reactivity against Pep01, Pep02 and Pep03 in different degrees. Mice immunization experiments showed that these peptides were able to induce a humoral response characterized by antibodies with low neutralizing activity. The spleen cells derived from mice immunized with the peptides showed a significant cytotoxic activity (only for Pep02 and Pep03), a high expression of IL-10 (P<0.01) and a reduced expression of TNF-α and IFN-gamma (P<0.001) compared to DENV-1 infected splenocytes. Thus these peptides, and specially the Pep03, can induce a humoral response characterized by antibodies with low neutralizing activities and probably a T cell response that could be beneficial to induce an effective immune response against all DENV serotypes and do not contributed to the immunopathogenesis. However, further studies in peptide sequence will be required to induce the production of neutralizing antibodies against all four DENV serotypes and also to improve immunogenicity of these peptides.
Laboratório de Vacinas, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Minas Gerais, Brazil.
Raissa Prado
RP
Rocha
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Minas Gerais, Brazil.
Márcia Cristina
MC
Livonesi
Laboratório de Vacinas, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Minas Gerais, Brazil.
Marcilio Jorge
MJ
Fumagalli
Laboratório de Vacinas, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Minas Gerais, Brazil.
Naiara Ferreira
NF
Rodrigues
Laboratório de Vacinas, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Minas Gerais, Brazil.
Lauro César Felipe
LC
da Costa
Laboratório de Vacinas, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Minas Gerais, Brazil.
Michelle Cristina Silva Gomes
MC
Dos Santos
Laboratório de Vírus, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
Eliseu Soares
ES
de Oliveira Rocha
Laboratório de Vírus, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
Erna Geessien
EG
Kroon
Laboratório de Vacinas, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Minas Gerais, Brazil.
Luiz Cosme Cotta
LC
Malaquias
Laboratório de Vacinas, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Minas Gerais, Brazil. Electronic address: coelho@unifal-mg.edu.br.
Luiz Felipe Leomil
LF
Coelho
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003601:Cytotoxicity Tests, Immunologic; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D051379:Mice; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D053059:Dengue Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins
Dengue virus; Envelope protein; Peptides; Vaccine