Humoral, mucosal, and cellular immunity in response to a human immunodeficiency virus type 1 immunogen expressed by a Venezuelan equine encephalitis virus vaccine vector

Abstract

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.

Heterologous Gene Expression from Transmissible Gastroenteritis Virus Replicon Particles

“…Consequently, E protein provided in trans should complement the E gene deletion and result in infectious TGEV VRPs. The VEE replicon system has been used previously for the high-level expression of a number of heterologous genes (3,11,34,58,59,67) and was used as an efficient means for expressing the TGEV E protein in trans. We hypothesized that VEE VRPs expressing TGEV E would supply sufficient concentrations of E protein in trans to allow for efficient assembly and release of packaged TGEV-Rep(AvrII) VRPs (Fig.…”

Mucosal immunity and tolerance: relevance to vaccine development

“…Recombinant vaccine strategies using RNA viruses such as poliovirus, alphaviruses (Venezuelan equine encephalitis virus (VEE), Semliki Forest virus), aud paramyxoviruses (RSV) as vectors are being actively explored for mucosal immunization. In particular, replication-competent VEE expressing HIV pl8 and p24 gag (179) or influenza virus HA genes (1 80) have been shown to induce mucosal and cellular immune responses. Interestingly, a replicon vaccine vector system was developed frcmi an attenuated strain of VEE (181), The replicon RNA consists of the cis-acting 5' and 3' ends of the VEE genome, the complete non-structural protein gene region, and the subgenomic 26S promoter.…”

Recombinant Vectors as Influenza Vaccines

“…5) (Schultz-Cherry et al 2000). VEE vaccines have also been developed for many other agents, including SIV, HIV, Lassa virus, Norwalk virus, Borrelia burgdorferi (the causative agent of Lyme disease), SARS-CoV, cowpox virus, dengue virus, and RSV (Caley et al 1997(Caley et al , 1999Pushko et al 1997;Davis et al 2000;Baric et al 2002;Harrington et al 2002;Gipson et al 2003;Johnston et al 2005;Deming et al 2006;Cecil et al 2007;Mok et al 2007;Thornburg et al 2007;White et al 2007). Further testing will determine whether VEE vaccine vectors are safe and efficacious in humans.…”