Abstract
Alphavirus vectors have demonstrated high levels of transient heterologous gene expression both in vitro and in vivo and, therefore, possess attractive features for vaccine development. The most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, namely Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus. Alphavirus vectors have been applied as replication-deficient recombinant viral particles and, more recently, as replication-proficient particles. Moreover, in vitro transcribed RNA, as well as layered DNA vectors have been applied for immunization. A large number of highly immunogenic viral structural proteins expressed from alphavirus vectors have elicited strong neutralizing antibody responses in multispecies animal models. Furthermore, immunization studies have demonstrated robust protection against challenges with lethal doses of virus in rodents and primates. Similarly, vaccination with alphavirus vectors expressing tumor antigens resulted in prophylactic protection against challenges with tumor-inducing cancerous cells. As certain alphaviruses, such as Chikungunya virus, have been associated with epidemics in animals and humans, attention has also been paid to the development of vaccines against alphaviruses themselves. Recent progress in alphavirus vector development and vaccine technology has allowed conducting clinical trials in humans.
Highlights
Alphaviruses are single-stranded RNA viruses with an envelope structure belonging to the family of Togaviridae [1]
Semliki Forest virus (SFV) [3] and Venezuelan equine encephalitis (VEE) virus [4] have been identified as the causes of an outbreak of febrile illness in Central Africa and an epidemic in horses and humans in South
Several alphaviruses, including SFV [5], Sindbis virus (SIN) [6] and VEE [7] have been subjected to the engineering of vectors for heterologous gene expression
Summary
Alphaviruses are single-stranded RNA viruses with an envelope structure belonging to the family of Togaviridae [1]. Despite this potential concern, several alphaviruses, including SFV [5], Sindbis virus (SIN) [6] and VEE [7] have been subjected to the engineering of vectors for heterologous gene expression. Vectors based on SFV, SIN and VEE have been applied as naked RNA, recombinant virus particles and layered DNA vectors [13]. In this context, viral and tumor antigens have been administered in various animal models to elicit neutralizing antibodies and protection against challenges with tumor cells or lethal doses of viruses. SP6, polymerase promoter; 26S, subgenomic alphavirus promoter; CMV, cytomegalovirus promoter; polyA tail, polyadenylation signal
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