Immunization of mice with recombinant vaccinia virus expressing authentic dengue virus nonstructural protein NS1 protects against lethal dengue virus encephalitis.
The protective immunity conferred by a set of recombinant vaccinia viruses containing the entire coding sequence of dengue virus type 4 nonstructural glycoprotein NS1 plus various flanking sequences was evaluated by using a mouse encephalitis model. Mice immunized with recombinant vNS1-NS2a, which expresses authentic NS1, were solidly protected against intracerebral dengue virus challenge. However, mice immunized with recombinants vNS1-15%NS2a and vRSVG/NS1-15%NS2a, which express aberrant forms of NS1, were only partially protected (63 to 67% survival rate). Serologic analysis showed that mice immunized with vNS1-NS2a developed high titers of antibodies to NS1 as measured by radioimmunoprecipitation, enzyme-linked immunosorbent assay, and complement-mediated cytolytic assays. In addition, a pool of sera from these animals was protective in a passive transfer experiment. Lower titers of NS1-specific antibodies were detected in sera of animals immunized with vNS1-15%NS2a or vRSVG/NS1-15%NS2a by all three assays. These data support the view that protection against dengue virus infection in mice may be mediated at least in part by NS1-specific antibodies through a mechanism of complement-mediated lysis of infected cells. Additionally, immunization with two recombinant viruses expressing authentic NS1 of dengue virus type 2 conferred partial protection (30-50%) against dengue virus type 2 challenge.
Falgout
B
B
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Bray
M
M
Schlesinger
J J
JJ
Lai
C J
CJ
D000818:Animals; D001483:Base Sequence; D002213:Capsid / Q000276:immunology*; D002460:Cell Line; D003001:Cloning, Molecular; D003715:Dengue / Q000276:immunology* / Q000517:prevention & control; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D004660:Encephalitis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D005260:Female; D006023:Glycoproteins; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011995:Recombination, Genetic; D015183:Restriction Mapping; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins
D006023:Glycoproteins; C000621009:NS1 protein, Dengue virus type 4; D015345:Oligonucleotide Probes; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins