title: Reduced immune responses after vaccination with a recombinant herpes simplex virus type 1 vector in the presence of antiviral immunity.
abstract: Due to the continuous need for new vaccines, viral vaccine vectors have become increasingly attractive. In particular, herpes simplex virus type 1 (HSV-1)-based vectors offer many advantages, such as broad cellular tropism, large DNA-packaging capacity and the induction of pro-inflammatory responses. However, despite promising results obtained with HSV-1-derived vectors, the question of whether pre-existing virus-specific host immunity affects vaccine efficacy remains controversial. For this reason, the influence of pre-existing HSV-1-specific immunity on the immune response induced with a replication-defective, recombinant HSV-1 vaccine was investigated in vivo. It was shown that humoral as well as cellular immune responses against a model antigen encoded by the vaccine were strongly diminished in HSV-1-seropositive mice. This inhibition could be observed in mice infected with wild-type HSV-1 or with a replication-defective vector. Although these data clearly indicate that pre-existing antiviral host immunity impairs the efficacy of HSV-1-derived vaccine vectors, they also show that vaccination under these constraints might still be feasible.
authors.affiliation: Institute for Immunology, Ludwig Maximilians University Munich, Goethestrasse 31, 80336 Munich, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Lauterbach
authors.affiliation: Institute for Immunology, Ludwig Maximilians University Munich, Goethestrasse 31, 80336 Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Ried
authors.affiliation: University Claude-Bernard Lyon 1, Centre de Genetique Moleculaire et Cellulaire, Lyon, France.
authors.forename: Alberto L
authors.initials: AL
authors.lastname: Epstein
authors.affiliation: University of Ferrara, Department of Experimental and Diagnostic Medicine, Ferrara, Italy.
authors.forename: Peggy
authors.initials: P
authors.lastname: Marconi
authors.affiliation: Institute for Immunology, Ludwig Maximilians University Munich, Goethestrasse 31, 80336 Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brocker
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011995:Recombination, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D022301:Herpes Simplex Virus Vaccines