A single intramuscular injection of recombinant plasmid DNA induces protective immunity and prevents Japanese encephalitis in mice.
Plasmid vectors containing Japanese encephalitis virus (JEV) premembrane (prM) and envelope (E) genes were constructed that expressed prM and E proteins under the control of a cytomegalovirus immediate-early gene promoter. COS-1 cells transformed with this plasmid vector (JE-4B clone) secreted JEV-specific extracellular particles (EPs) into the culture media. Groups of outbred ICR mice were given one or two doses of recombinant plasmid DNA or two doses of the commercial vaccine JEVAX. All mice that received one or two doses of DNA vaccine maintained JEV-specific antibodies 18 months after initial immunization. JEVAX induced 100% seroconversion in 3-week-old mice; however, none of the 3-day-old mice had enzyme-linked immunosorbent assay titers higher than 1:400. Female mice immunized with this DNA vaccine developed plaque reduction neutralization antibody titers of between 1:20 and 1:160 and provided 45 to 100% passive protection to their progeny following intraperitoneal challenge with 5,000 PFU of virulent JEV strain SA14. Seven-week-old adult mice that had received a single dose of JEV DNA vaccine when 3 days of age were completely protected from a 50, 000-PFU JEV intraperitoneal challenge. These results demonstrate that a recombinant plasmid DNA which produced JEV EPs in vitro is an effective vaccine.
Chang
G J
GJ
Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Fort Collins, Colorado 80522, USA. gxc7@cdc.gov
Hunt
A R
AR
Davis
B
B
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D019556:COS Cells; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D004274:DNA, Recombinant; D004279:DNA, Viral; D004195:Disease Models, Animal; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000517:prevention & control*; D018604:Epitope Mapping; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D007112:Immunity, Maternally-Acquired; D007273:Injections, Intramuscular; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D010957:Plasmids; D011061:Poly A; D011401:Promoter Regions, Genetic; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D004274:DNA, Recombinant; D004279:DNA, Viral; D008562:Membrane Glycoproteins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C080628:glycoprotein E, Japanese encephalitis virus; C074932:prM protein, Flavivirus; D011061:Poly A