Attenuation of Chikungunya Virus Vaccine Strain 181/Clone 25 Is Determined by Two Amino Acid Substitutions in the E2 Envelope Glycoprotein

• DOI: 10.1128/jvi.06449-11
• Publication Date: 2012-03-29T02:35:51Z
• Authors: Rodion Gorchakov; Eryu Wang; Grace Leal; Naomi L. Forrester; Kenneth Plante; Shannan L. Rossi; Charalambos D. Pa...; A. Paige Adams; Robert L. Seymour; James Weger; Erin M. Borland; Michael B. Sherman; Ann M. Powers; Jorge E. Osorio; Scott C. Weaver
• Keywords: Envelope (radar); clone (Java method); Strain (injury)

Chikungunya virus (CHIKV) is the mosquito-borne alphavirus that etiologic agent of massive outbreaks arthralgic febrile illness recently affected millions people in Africa and Asia. The only CHIKV vaccine has been tested humans, strain 181/clone 25, a live-attenuated derivative Southeast Asian human isolate AF15561. was immunogenic phase I II clinical trials; however, it induced transient arthralgia 8% vaccinees. There are five amino acid differences between its parent, as well synonymous mutations, none which involves cis-acting genome regions known to be responsible for replication or packaging. To identify determinants attenuation, we therefore nonsynonymous mutations by cloning them individually different combinations into infectious clones derived from two wild-type (WT) strains, La Reunion Levels virulence were compared with those WT strains murine models: infant CD1 adult A129 mice. An attenuated phenotype indistinguishable 25 obtained simultaneous expression E2 glycoprotein substitutions, intermediate levels attenuation single mutations. other three nsP1, 6K, E1, did not have detectable effect on virulence. These results indicate mediated point explaining phenotypic instability observed vaccinees also our studies.