Vaccination with the immediate-early protein ICP47 of herpes simplex virus-type 1 (HSV-1) induces virus-specific lymphoproliferation, but fails to protect against lethal challenge.
Assessing the immunobiological function of the individual proteins of herpes simplex virus-type 1 (HSV-1) continues to be important in elucidating virus-host interactions and for the rational design of subunit vaccines. In this report, the non-structural, immediate-early protein ICP47 of HSV-1 was examined for its ability to induce virus-specific immune responses. The ICP47 protein, when expressed from a recombinant vaccinia virus or when produced by cell-free, in vitro translation, induced a vigorous HSV-1-specific lymphoproliferative response. However, other common parameters of immunity such as neutralizing antibody, delayed-type hypersensitivity, and class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) were not induced by ICP47. Moreover, mice immunized with vaccinia-expressed ICP47 were unable to survive lethal challenge with virulent HSV, indicating that in spite of its ability to induce significant HSV-1-specific lymphoproliferation, ICP47 appears unable to afford protective immunity in vivo. Possible reasons for this failure and the implications of these results in terms of vaccine design are discussed.
Banks
T A
TA
Department of Microbiology, University of Tennessee, Knoxville 37996-0845.
Jenkins
F J
FJ
Kanangat
S
S
Nair
S
S
Dasgupta
S
S
Foster
C M
CM
Rouse
B T
BT
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001483:Base Sequence; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D006561:Herpes Simplex / Q000517:prevention & control*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D017874:Immediate-Early Proteins / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008809:Mice, Inbred C3H / Q000276:immunology; D008810:Mice, Inbred C57BL / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins / Q000276:immunology; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014616:Vaccinia virus / Q000235:genetics; D014764:Viral Proteins
D000914:Antibodies, Viral; D006183:H-2 Antigens; C105843:ICP47 protein, Herpes simplex virus; C050678:IE1 protein, Human herpesvirus 1; D017874:Immediate-Early Proteins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins