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8th Conference on Retroviruses and Opportunistic Infections
Chicago, IL - February 4 - 8, 2001
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The biology of alphavirus vectors and their use as vaccines for HIV
Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:282 (abstract no. S7)
Johnston RE; Univ of North Carolina, Chapel Hill.
An expression system based on the alphavirus Venezuelan equine encephalitis virus (VEE) has been constructed. The RNA genome of VEE, in the form of a cDNA clone, is modified by substituting a gene of interest for the genes encoding the capsid and two glycoproteins which form the virion structure. In vitro transcripts of the modified genome ( a replicon) are electroporated into cells where the replicase genes of the virus catalyze the synthesis of large amounts of an mRNA for the gene of interest. The replicon genome is packaged into replicon particles (VRP), identical to the virus itself, by supplying the capsid and glycoprotein genes on helper RNAs co-electroporated with the replicon RNA. VRP expressing the SIVsmH4 gag, env and pol genes have been used to immunize macaques followed by intravenous (i.v.) or intrarectal (i.r.) challenge with SIVsmE660. Measurable protection was obtained in both challenge models. Upon subcutaneous inoculation into mice, VRP home to the draining lymph node where they produce the immunogen. VRP enveloped with wild-type VEE glycoproteins efficiently infected dendritic cells and were extremely efficient in inducing both humoral and cellular immune responses. While VRP enveloped with three different mutant glycoproteins varied dramatically with respect to the efficiency of dendritic cell targeting as well as the efficiency of induced immune responses, analysis of a larger number of glycoprotein mutants will be required to determine whether dendritic cell targeting and efficient induction of immune responses are correlated.
Keywords: AEGIS, Alphavirus, Encephalitis Virus, Venezuelan Equine, Vaccines, Encephalomyelitis, Venezuelan Equine, Replicon, HIV, Vaccination, Viral Vaccines, Vaccines, Synthetic, Capsid, Vaccines, Attenuated, Vaccines, Combined, Virion, Vaccines, DNA, RNA, In Vitro, Animal, Mice, utilization, genetics, AIDS
2001-02-04
S7
Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.