Arenavirus Vaccine

University Of California-Irvine, Irvine CA

Investigators

Linked publications & trials

Abstract

Arenaviruses of the old and new world share considerable similarity in their overall structure and genomic sequence, and this is reflected by the presence of numerous shared B and T-cell epitopes predicted by contemporary epitope prediction algorithms, and observed in cross protection studies in animals. Two such examples of this are the observed protection of primates and guinea pigs against Lassa virus by prior exposure to LCM virus, and the broad protective effect of live attenuated Junin Vaccine against both Junin and Machupo viruses. We have identified common and highly conserved CD-8 T-cell epitopes shared by old and new world arenaviruses as well as others shared only within each of these groups respectively. It is proposed that we will establish a standardized protocol for delivery of these relevant epitopes and explore the fine specificity requirements needed to establish successful protective responses. We will also establish a structural basis for the protective effect exerted by the live attenuated Junin Candid 1 vaccine. This vaccine was developed jointly by the US Army and Argentine Scientists in the 1980's and has been highly successful in human use in Argentina. To date it is the only vaccine for arenavirus infection, Despite this success the vaccine has fallen out of production and its future availability is uncertain. We will first sequence reference stocks of the vaccine strain to determine it's genetic homogeneity and divergence from wt strains of Junin studied previously by the StJeor and Buchmeier labs, then we will study the in vivo response to vaccination at the genomic and epitopic level in order to understand the protective response. These data as well as knowledge of the requirements for protection against arenavirus disease will be used to construct a broad spectrum arenavirus vaccine.