Mucosal immunization with Salmonella typhimurium expressing Lassa virus nucleocapsid protein cross-protects mice from lethal challenge with lymphocytic choriomeningitis virus

Objectives: Lassa fever virus (WS) is transmitted to man by rodent carriers and is fatal in a third of untreated cases. Our goal is to provide immune protection from Lassa fever by mucosal vaccination. Study Design/Methods: Mice were vaccinated intragastrically with control ve ctors or with vectors (vaccinia or Salmonella) expressing LAS nucleocapsid protein (NP). Mice were challenged intracranially with a lethal dose of the related arenavirus,, lymphocytic choriomeningitis virus (LCMV), as a measu re of the vaccine's ability to elicit cross-protection Results: Salmonella and vaccinia vectors expressing WS NP each protected a third of the mice from lethal challenge with LCMV. All mice vaccinated with a vector expressing LCMV NP were protected as expected. Conclusions: The LAS recombinant Salmonella vector is comparable to the WS recombinant vaccinia vector in its ability to cross-protect mice from letha l challenge, Nucleocapsid protein is an inadequate immunogen on its own, bu t provides sufficient cross-protection to make it a useful component of a b roadly reactive arenavirus vaccine.