Enhancing immune responses using suicidal DNA vaccines.
We describe a DNA vaccine strategy that allows antigens to be produced in vivo in the context of an alphaviral replicon. Mice immunized with such vectors developed humoral and cellular immune responses at higher levels than mice that received a conventional DNA vaccine vector. Immunized animals acquired protective immunity to lethal influenza challenge. Compared with traditional DNA vaccine strategies in which vectors are persistent and the expression constitutive, the expression mediated by the alphaviral vector was transient and lytic. As a result, biosafety risks such as chromosomal integration, and the induction of immunological tolerance, could be circumvented.
Berglund
P
P
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
Smerdou
C
C
Fleeton
M N
MN
Tubulekas
I
I
Liljeström
P
P
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation; D002460:Cell Line; D006224:Cricetinae; D003588:Cytopathogenic Effect, Viral; D004274:DNA, Recombinant / Q000235:genetics; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D005822:Genetic Vectors / Q000276:immunology; D007111:Immunity, Cellular; D009980:Influenza A virus / Q000276:immunology; D007668:Kidney; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D012093:Replicon / Q000276:immunology; D012672:Semliki forest virus / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000737:chemistry / Q000276:immunology*
D000276:Adjuvants, Immunologic; D004274:DNA, Recombinant; D019444:Vaccines, DNA