Autor(es): Lam Shirley, Nyo Min, Phuektes Patchara, Yew Chow Wenn, Tan Yee Joo, Chu Justin Jang Hann

Resumo: Chikungunya virus (CHIKV) is a medically important human viral pathogen that causes Chikungunya fever accompanied with debilitating - persistent joint pain. Host-elicited or passively-transferred monoclonal antibodies (mAb) are essential mediators of CHIKV clearance. Therefore, this study aimed to generate - characterize a panel of mAbs for their neutralization efficacy against CHIKV infection in a cell-based - murine model. To evaluate their antigenicity - neutralization profile, indirect enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay (IFA) - a plaque reduction neutralization test were performed on mAbs of IgM isotype. CHIKV escape mutants against mAb 3E7b neutralization were generated, - reverse genetics techniques were then used to create an infectious CHIKV clone with a single mutation. 3E7b was also administered to neonate mice prior or after CHIKV infection. The survival rate, CHIKV burden in tissues - histopathology of the limb muscles were evaluated. Both IgM 3E7b - 8A2c bind strongly to native CHIKV surface - potently neutralize CHIKV replication. Further analyses of 3E7b binding - neutralization of CHIKV single-mutant clones revealed that N218 of CHIKV E2 protein is a potent neutralizing epitope. In a pre-binding neutralization assay, 3E7b blocks CHIKV attachment to permissive cells, possibly by binding to the surface-accessible E2-N218 residue. Prophylactic administration of 3E7b to neonate mice markedly reduced viremia - protected against CHIKV pathogenesis in various mice tissues. Given therapeutically at 4 h post-infection, 3E7b conferred 100% survival rate - similarly reduced CHIKV load in most mice tissues except the limb muscles. Collectively, these findings highlight the usefulness of 3E7b for future prophylactic or epitope-based vaccine design.

Palavras-Chave: Envelope 2 protein; Epitope; Monoclonal antibody; Virus pathogenesis

Imprenta: mAbs, v. 7, n. 6, p. 1178-1194, 2015

Identificador do objeto digital: 10.1080/19420862.2015.1083664

Descritores: Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - RNA ; Chikungunya virus - Antibodies ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever

Data de publicação: 2015