Abstract
Alphaviruses have been engineered as vectors for high-level transgene expression. Originally, alphavirus-based vectors were applied as recombinant replication-deficient particles, subjected to expression studies in mammalian and non-mammalian cell lines, primary cell cultures, and in vivo. However, vector engineering has expanded the application range to plasmid DNA-based delivery and expression. Immunization studies with DNA-based alphavirus vectors have demonstrated tumor regression and protection against challenges with infectious agents and tumor cells in animal tumor models. The presence of the RNA replicon genes responsible for extensive RNA replication in the RNA/DNA layered alphavirus vectors provides superior transgene expression in comparison to conventional plasmid DNA-based expression. Immunization with alphavirus DNA vectors revealed that 1000-fold less DNA was required to elicit similar immune responses compared to conventional plasmid DNA. In addition to DNA-based delivery, immunization with recombinant alphavirus particles and RNA replicons has demonstrated efficacy in providing protection against lethal challenges by infectious agents and tumor cells.
Highlights
The classic approach for the development of vaccines for infectious diseases has comprised of immunization with live attenuated or inactivated agents [1]
Numerous immunization studies conducted with recombinant alphavirus replicon particles have been described previously [34] and as the focus on this review is on DNA-based alphavirus vectors, only two examples of comparative studies on replicon particles and DNA vectors are presented here
Vectors expressing the influenza type A virus nucleoprotein (NP) were intramuscularly administered in C57BL/6 mice [40]. Both rSFV-NP and rDELTA1-E-NP elicited antibodies against the influenza virus NP, but cytotoxic T-lymphocyte (CTL) responses against the immunodominant H-2D(b) epitope NP366 was only obtained with the Semliki Forest virus (SFV) replicon RNA
Summary
The classic approach for the development of vaccines for infectious diseases has comprised of immunization with live attenuated or inactivated agents [1]. The introduction of genetic engineering expanded the approaches of vaccine development to the application of recombinantly expressed antigens and immunogens as immunization agents [2]. Both viral and non-viral vectors expressing surface proteins and antigens have been used for immunization, first in animal models followed by human clinical trials [3]. Taking this approach has elicited strong humoral and cellular immune responses and has provided protection against challenges with lethal doses of infectious agents [4]. The basics of the self-amplifying replicon function is briefly described below
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