Role of genes that modulate host immune responses in the immunogenicity and pathogenicity of vaccinia virus.
Poxvirus vaccine vectors, although capable of eliciting potent immune responses, pose serious health risks in immunosuppressed individuals. We therefore constructed five novel recombinant vaccinia virus vectors which contained overlapping deletions of coding regions for the B5R, B8R, B12R, B13R, B14R, B16R, B18R, and B19R immunomodulatory gene products and assessed them for both immunogenicity and pathogenicity. All five of these novel vectors elicited both cellular and humoral immunity to the inserted HIV-BH10 env comparable to that induced by the parental Wyeth strain vaccinia virus. However, deletion of these immunomodulatory genes did not increase the immunogenicity of these vectors compared with the parental vaccinia virus. Furthermore, four of these vectors were slightly less virulent and one was slightly more virulent than the Wyeth strain virus in neonatal mice. Attenuated poxviruses have potential use as safer alternatives to current replication-competent vaccinia virus. Improved vaccinia virus vectors can be generated by deleting additional genes to achieve a more significant viral attenuation.
Jackson
Shawn S
SS
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Research East -RE 113, 330 Brookline Ave., Boston, Massachusetts 02215, USA.
Ilyinskii
Petr
P
Philippon
Valérie
V
Gritz
Linda
L
Yafal
Alicia Gómez
AG
Zinnack
Kimberly
K
Beaudry
Kristin R
KR
Manson
Kelledy H
KH
Lifton
Michelle A
MA
Kuroda
Marcelo J
MJ
Letvin
Norman L
NL
Mazzara
Gail P
GP
Panicali
Dennis L
DL
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D005260:Female; D017353:Gene Deletion; D005822:Genetic Vectors / Q000235:genetics*; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000276:immunology*; D007114:Immunization; D007117:Immunization, Secondary; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D014614:Vaccines, Synthetic