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P12-15. Replication enhancement of an alphaviral-lentiviral replicating chimeric particle (RCP) vaccine

Authors
Journal
Retrovirology
1742-4690
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Volume
6
Identifiers
DOI: 10.1186/1742-4690-6-s3-p181
Keywords
  • Poster Presentation
Disciplines
  • Biology
  • Medicine

Abstract

1742-4690-6-S3-P181.fm BioMed Central Page 1 of 1 (page number not for citation purposes) Retrovirology Open AccessPoster presentation P12-15. Replication enhancement of an alphaviral-lentiviral replicating chimeric particle (RCP) vaccine K Young*2, C Beard1 and R Johnston2 Address: 1Global Vaccines, Inc., Research Triangle Park, USA and 2University of North Carolina-Chapel Hill and Global Vaccines, Inc., Chapel Hill and Durham, NC, USA * Corresponding author Background We have developed a novel, acutely replicating VEE-SHIV chimeric particle (RCP) as a vaccine against HIV that com- bines the superior and long-lived immunity of a live- attenuated virus with the safety of non-replicating partic- ulate antigens. These chimeric particles contain a replicat- ing VEE-SHIV genome and are capable of infecting susceptible cells bearing hCD4/hCCR5, undergoing cyto- plasmic replication, genomic RNA encapsidation, assem- bly and particle release. Due to the replicative nature of the RCPs, lentiviral proteins will be expressed for an extended period of time in vaccinated individuals thus inducing a more comprehensive immune response com- pared to nonreplicating antigens but without the safety issues associated with integrating, live-attenuated lentivi- ruses. Methods VEE-SHIV RCP vaccines contain the VEE UTRs along with nonstructural genes required for RNA replication. Struc- tural genes of VEE, which are under the control of the VEE subgenomic 26S promoter, were replaced with SIV gag +/ - an attenuated protease (PR, A28S). The VEE capsid frag- ment (aa75-132), predicted to bind VEE genomic RNA, was incorporated by replacing the NC region of gag while maintaining the proteolytic cleavage sites. HIV Env was added downstream from a second VEE subgenomic pro- moter. Results VEE-SHIV RCP vaccines were evaluated for particle forma- tion, encapsidation of genomic RNA and infectivity in both primate and rodent. Inclusion of the VEE C fragment and attenuated protease in the VEE-SHIV RCP i

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