A small antigenic determinant of the Chikungunya virus E2 protein is sufficient to induce neutralizing antibodies which are partially protective in mice.
Autor(es): Weber Christopher, Büchner Sarah M, Schnierle Barbara S
Resumo: The mosquito-borne Chikungunya virus (CHIKV) causes high fever - severe joint pain in humans. It is expected to spread in the future to Europe - has recently reached the USA due to globalization, climate change - vector switch. Despite this, little is known about the virus life cycle -, so far, there is no specific treatment or vaccination against Chikungunya infections. We aimed here to identify small antigenic determinants of the CHIKV E2 protein able to induce neutralizing immune responses. E2 enables attachment of the virus to target cells - a humoral immune response against E2 should protect from CHIKV infections. Seven recombinant proteins derived from E2 - consisting of linear -/or structural antigens were created, - were expressed in - purified from E. coli. BALB/c mice were vaccinated with these recombinant proteins - the mouse sera were screened for neutralizing antibodies. Whereas a linear N-terminally exposed peptide (L) - surface-exposed parts of the E2 domain A (sA) alone did not induce neutralizing antibodies, a construct containing domain B - a part of the ?-ribbon (called B+) was sufficient to induce neutralizing antibodies. Furthermore, domain sA fused to B+ (sAB+) induced the highest amount of neutralizing antibodies. Therefore, the construct sAB+ was used to generate a recombinant modified vaccinia virus Ankara (MVA), MVA-CHIKV-sAB+. Mice were vaccinated with MVA-CHIKV-sAB+ -/or the recombinant protein sAB+ - were subsequently challenged with wild-type CHIKV. Whereas four vaccinations with MVA-CHIKV-sAB+ were not sufficient to protect mice from a CHIKV infection, protein vaccination with sAB+ markedly reduced the viral titers of vaccinated mice. The recombinant protein sAB+ contains important structural antigens for a neutralizing antibody response in mice - its formulation with appropriate adjuvants might lead to a future CHIKV vaccine.
Imprenta: PLoS Neglected Tropical Diseases, v. 9, n. 4, p. e0003684, 2015
Identificador do objeto digital: 10.1371/journal.pntd.0003684
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Immune response ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Immune response ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Immunology
Data de publicação: 2015
