Novel recombinant parapoxvirus vectors induce protective humoral and cellular immunity against lethal herpesvirus challenge infection in mice.
Orf virus (ORFV; Parapoxvirus ovis) was used to develop a novel vector system for the generation of effective and safe live vaccines. Based on the attenuated ORFV strain D1701-V, recombinants were produced that express the glycoproteins gC (D1701-VrVgC) or gD (D1701-VrVgD) of the alphaherpesvirus of swine, pseudorabies virus (PRV). Expression of gC and gD was also demonstrated on the surface of recombinant virus-infected murine cells that do not produce infectious ORFV. Single or combined immunization with the ORFV recombinants protected different mouse strains of a host species nonpermissive for ORFV against a fulminant, lethal PRV challenge infection equal to immunization with PRV live vaccine. Most notably, even a single immunization with D1701-VrVgC was protective, whereas two applications of D1701-VrVgD were required for immune protection. The higher protective capacity of D1701-VrVgC correlated with the induction of a strong specific humoral immune response. This suggestion was supported by transfer experiments using sera from recombinant-immunized mice, which resulted in partial gC but not gD antibody-mediated protection of the naïve recipients. Remarkably, immunization of different immune-deficient mice demonstrated that the application of the PRV gC-expressing recombinant controlled the challenge infection in the absence of either CD4(+) or CD8(+) T cells, B cells, or an intact perforin pathway. In contrast, D1701-VrVgD-immunized mice lacking CD4(+) T cells exhibited reduced protection, whereas animals lacking CD8(+) T cells, B cells, or perforin resisted the challenge infection. The present study demonstrates the potential of these new vector vaccines to efficiently prime both protective humoral and cell-mediated immune mechanisms in a host species nonpermissive for the vector virus.
Fischer
Timo
T
Federal Research Centre for Virus Diseases of Animals, Institute of Immunology, D-72076 Tuebingen, Germany.
Planz
Oliver
O
Stitz
Lothar
L
Rziha
Hanns-Joachim
HJ
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D005822:Genetic Vectors; D016679:Genome, Viral; D011558:Herpesvirus 1, Suid / Q000235:genetics* / Q000276:immunology*; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018157:Parapoxvirus / Q000235:genetics*; D011557:Pseudorabies / Q000276:immunology / Q000517:prevention & control; D011995:Recombination, Genetic; D014614:Vaccines, Synthetic / Q000235:genetics / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000494:pharmacology
D000914:Antibodies, Viral; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C107752:glycoprotein D, pseudorabies virus; C042966:pseudorabies virus glycoproteins