Mucosal immunization with Salmonella typhimurium expressing Lassa virus nucleocapsid protein cross-protects mice from lethal challenge with lymphocytic choriomeningitis virus.
OBJECTIVE
Lassa fever virus (LAS) 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.


METHODS
Mice were vaccinated intragastrically with control vectors 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 measure of the vaccine's ability to elicit cross-protection.


RESULTS
Salmonella and vaccinia vectors expressing LAS 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 LAS recombinant vaccinia vector in its ability to cross-protect mice from lethal challenge. Nucleocapsid protein is an inadequate immunogen on its own, but provides sufficient cross-protection to make it a useful component of a broadly reactive arenavirus vaccine.
Djavani
M
M
Institute of Human Virology, University of Maryland Biotechnology Center, Baltimore 21201, USA.
Yin
C
C
Lukashevich
I S
IS
Rodas
J
J
Rai
S K
SK
Salvato
M S
MS
D000818:Animals; D002213:Capsid / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins; D003429:Cross Reactions; D005822:Genetic Vectors; D018928:Immunity, Mucosal; D007114:Immunization; D007835:Lassa Fever / Q000517:prevention & control; D007836:Lassa virus / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000517:prevention & control*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012486:Salmonella typhimurium / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics; D014765:Viral Vaccines / Q000276:immunology*
D036022:Capsid Proteins; D014765:Viral Vaccines; C110151:nucleocapsid protein, lassa virus