Evaluating the immunogenicity and protective efficacy of a DNA vaccine encoding Lassa virus nucleoprotein.
Several viruses in the Arenavirus genus of the family Arenaviridae cause severe, often fatal, hemorrhagic fever. One such virus, Lassa virus (LV), is a frequent cause of disease in Africa, and survivors often are left with substantial neurological impairment. The feasibility of protective immunization against LV infection, and the associated disease, has been demonstrated in animal models, using recombinant vaccinia viruses to deliver Lassa proteins. Circumstantial evidence implicates cellular immunity in this Lassa-induced protection, but this has not been confirmed. Here, we describe DNA vaccines that encode LV proteins. A single inoculation of a plasmid encoding full-length Lassa nucleoprotein (LNP) can induce CD8(+) T cell responses in mice and can protect against challenge with two arenaviruses, lymphocytic choriomeningitis virus (LCMV) and Pichinde virus (PV). A DNA minigene vaccine encoding a 9 amino acid sequence from LNP also induces CD8(+) T cells and protects against arenavirus challenge, thus confirming prior speculation that protective cellular immunity is induced by LV proteins.
Rodriguez-Carreno
Maria P
MP
Department of Neuropharmacology, CVN-9, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Nelson
Michael S
MS
Botten
Jason
J
Smith-Nixon
Kim
K
Buchmeier
Michael J
MJ
Whitton
J Lindsay
JL
D000595:Amino Acid Sequence; D000818:Animals; D001117:Arenaviridae Infections / Q000517:prevention & control* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007114:Immunization; D007836:Lassa virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000517:prevention & control* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D018052:Pichinde virus / Q000472:pathogenicity; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
D009698:Nucleoproteins; D019444:Vaccines, DNA; D014764:Viral Proteins; D014765:Viral Vaccines