Humoral, mucosal, and cellular immunity in response to a human immunodeficiency virus type 1 immunogen expressed by a Venezuelan equine encephalitis virus vaccine vector.
A molecularly cloned attenuated strain of Venezuelan equine encephalitis virus (VEE) has been genetically configured as a replication-competent vaccine vector for the expression of heterologous viral proteins (N. L. Davis, K. W. Brown, and R. E. Johnston, J. Virol. 70:3781-3787, 1996). The matrix/capsid (MA/CA) coding domain of human immunodeficiency virus type 1 (HIV-1) was cloned into the VEE vector to determine the ability of a VEE vector to stimulate an anti-HIV immune response in mice. The VEE-MA/CA vector replicated rapidly in the cytoplasm of baby hamster kidney (BHK) cells and expressed large quantities of antigenically identifiable MA/CA protein. When injected subcutaneously into BALB/c mice, the vector invaded and replicated in the draining lymphoid tissues, expressing HIV-1 MA/CA at a site of potent immune activity. Anti-MA/CA immunoglobulin G (IgG) and IgA antibodies were present in serum of all immunized mice, and titers increased after a second booster inoculation. IgA antibodies specific for MA/CA were detected in vaginal washes of mice that received two subcutaneous immunizations. Cytotoxic T-lymphocyte responses specific for MA/CA were detected following immunization with the MA/CA-expressing VEE vector. These findings demonstrate the ability of a VEE-based vaccine vector system to stimulate a comprehensive humoral and cellular immune response. The multifaceted nature of this response makes VEE an attractive vaccine for immunization against virus infections such as HIV-1, for which the correlates of protective immunity remain unclear, but may include multiple components of the immune system.
Caley
I J
IJ
Department of Microbiology, School of Medicine, University of North Carolina, Chapel Hill 27599, USA.
Betts
M R
MR
Irlbeck
D M
DM
Davis
N L
NL
Swanstrom
R
R
Frelinger
J A
JA
Johnston
R E
RE
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D002213:Capsid / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D003601:Cytotoxicity Tests, Immunologic; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics* / Q000276:immunology; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D014621:Vagina / Q000276:immunology* / Q000473:pathology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D015683:Gene Products, gag; D015483:HIV Antibodies; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins