HSV-1 amplicon vectors launch the production of heterologous rotavirus-like particles and induce rotavirus-specific immune responses in mice.
Virus-like particles (VLPs) are promising vaccine candidates because they represent viral antigens in the authentic conformation of the virion and are therefore readily recognized by the immune system. As VLPs do not contain genetic material they are safer than attenuated virus vaccines. In this study, herpes simplex virus type 1 (HSV-1) amplicon vectors were constructed to coexpress the rotavirus (RV) structural genes VP2, VP6, and VP7 and were used as platforms to launch the production of RV-like particles (RVLPs) in vector-infected mammalian cells. Despite the observed splicing of VP6 RNA, full-length VP6 protein and RVLPs were efficiently produced. Intramuscular injection of mice with the amplicon vectors as a two-dose regimen without adjuvants resulted in RV-specific humoral immune responses and, most importantly, immunized mice were partially protected at the mucosal level from challenge with live wild-type (wt) RV. This work provides proof of principle for the application of HSV-1 amplicon vectors that mediate the efficient production of heterologous VLPs as genetic vaccines.
Institute of Virology, University of Zurich, Zurich, Switzerland.
Andrea S
AS
Laimbacher
Laboratoria de Inmunologia y Virologia, Universidad Nacional de Quilmes, Bernal, Argentina.
Laura E
LE
Esteban
Laboratoria de Inmunologia y Virologia, Universidad Nacional de Quilmes, Bernal, Argentina.
Alejandro A
AA
Castello
Laboratoria de Inmunologia y Virologia, Universidad Nacional de Quilmes, Bernal, Argentina.
Juan C
JC
Abdusetir Cerfoglio
Laboratoria de Inmunologia y Virologia, Universidad Nacional de Quilmes, Bernal, Argentina.
Marcelo H
MH
Argüelles
Laboratoria de Inmunologia y Virologia, Universidad Nacional de Quilmes, Bernal, Argentina.
Graciela
G
Glikmann
Centro de Virología Animal, Instituto de Ciencia y Tecnología, Buenos Aires, Argentina.
Alejandra
A
D'Antuono
Centro de Virología Animal, Instituto de Ciencia y Tecnología, Buenos Aires, Argentina.
Nora
N
Mattion
Sección Virología, Universidad de la República, Montevideo, Uruguay.
Mabel
M
Berois
Sección Virología, Universidad de la República, Montevideo, Uruguay.
Juan
J
Arbiza
Institute of Pathology, University of Zurich, Zurich, Switzerland.
Monika
M
Hilbe
Institute of Virology, University of Zurich, Zurich, Switzerland.
Elisabeth M
EM
Schraner
Institute of Virology, University of Zurich, Zurich, Switzerland.
Michael
M
Seyffert
Institute of Virology, University of Zurich, Zurich, Switzerland.
Christiane
C
Dresch
Université de Lyon, Lyon, France; CNRS, UMR5534, Centre de Génétique et Physiologie Moléculaires et Cellulaires, Villeurbanne, France.
Alberto L
AL
Epstein
Institute of Virology, University of Zurich, Zurich, Switzerland.
Mathias
M
Ackermann
Institute of Virology, University of Zurich, Zurich, Switzerland. Electronic address: cornel.fraefel@access.uzh.ch.
Cornel
C
Fraefel
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D002522:Chlorocebus aethiops; D005260:Female; D005822:Genetic Vectors; D057809:HEK293 Cells; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007114:Immunization; D051379:Mice; D012401:Rotavirus / Q000235:genetics / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology / Q000517:prevention & control*; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014709:Vero Cells; D014771:Virion / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; C442545:VP2 protein, Rotavirus; C061332:VP6 protein, Rotavirus; C050779:VP7 protein, Rotavirus; D058425:Vaccines, Virus-Like Particle