Identifying the role of E2 domains on alphavirus neutralization and protective immune responses
Autor(es): Weger-Lucarelli James, Aliota Matthew T, Kamlangdee Attapon, Osorio Jorge E
Resumo: Chikungunya virus (CHIKV) - other alphaviruses are the etiologic agents of numerous diseases in both humans - animals. Despite this, the viral mediators of protective immunity against alphaviruses are poorly understood, highlighted by the lack of a licensed human vaccine for any member of this virus genus. The alphavirus E2, the receptor-binding envelope protein, is considered to be the predominant target of the protective host immune response. Although envelope protein domains have been studied for vaccine - neutralization in flaviviruses, their role in alphaviruses is less characterized. Here, we describe the role of the alphavirus E2 domains in neutralization - protection through the use of chimeric viruses. Four chimeric viruses were constructed in which individual E2 domains of CHIKV were replaced with the corresponding domain from Semliki Forest virus (SFV) (?DomA/?DomB/?DomC/ ?DomA+B). Vaccination studies in mice (both live - inactivated virus) revealed that domain B was the primary determinant of neutralization. Neutralization studies with CHIKV immune serum from humans were consistent with mouse studies, as ?DomB was poorly neutralized. Using chimeric viruses, it was determined that the alphavirus E2 domain B was the critical target of neutralizing antibodies in both mice - humans. Therefore, chimeric viruses may have more relevance for vaccine discovery than peptide-based approaches, which only detect linear epitopes. This study provides new insight into the role of alphavirus E2 domains on neutralization determinants - may be useful for the design of novel therapeutic technologies.
Imprenta: PLoS Neglected Tropical Diseases, v. 9, n. 10, p. e0004163, 2015
Identificador do objeto digital: 10.1371/journal.pntd.0004163
Descritores: Chikungunya virus - Immune response ; Chikungunya virus - Antibodies ; Chikungunya virus - Immune response ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine
Data de publicação: 2015
