HSV-1 amplicon vectors

LAIMBACHER A; ESTEBAN L; CASTELLO A; ABDUSETIR J; ARGÜELLES M; GLIKMANN G; D'ANTUONO A; MATTION N; BEROIS M; ARBIZA J; HILBE M; SCHRANER E; SEYFFERT M; DRESCH C; EPSTEIN A; ACKERMAN M; FRAEFEL C

MOLECULAR THERAPY (PRINT)

NATURE PUBLISHING GROUP

Año: 2011 p. 1 - 11

1525-0016

Virus-like particles (VLPs) are promising vaccine candidates because they represent viralantigens in the authentic conformation of the virion and are therefore readily recognized bythe immune system. As VLPs do not contain genetic material they are safer than attenuatedvirus vaccines. In this study, herpes simplex virus type 1 (HSV-1) amplicon vectors wereconstructed to co-express the rotavirus (RV) structural genes VP2, VP6, and VP7 and wereused as platforms to launch the in situ production of rotavirus-like particles (RVLPs) invector-infected mammalian cells. Despite the observed splicing of VP6 RNA, full-length VP6protein and RVLPs were efficiently produced. Intramuscular injection of mice with theamplicon vectors as a two-dose regimen without adjuvants resulted in RV-specific humoralimmune responses. Immunized mice were partially protected from challenge with wild typeRV, as shedding of RV antigen in stool was significantly reduced. This work provides proof ofprinciple for the application of HSV-1 amplicon vectors as genetic vaccines that mediate theefficient production of heterologous VLPs