Heterologous protection against influenza by injection of DNA encoding a viral protein.
Cytotoxic T lymphocytes (CTLs) specific for conserved viral antigens can respond to different strains of virus, in contrast to antibodies, which are generally strain-specific. The generation of such CTLs in vivo usually requires endogenous expression of the antigen, as occurs in the case of virus infection. To generate a viral antigen for presentation to the immune system without the limitations of direct peptide delivery or viral vectors, plasmid DNA encoding influenza A nucleoprotein was injected into the quadriceps of BALB/c mice. This resulted in the generation of nucleoprotein-specific CTLs and protection from a subsequent challenge with a heterologous strain of influenza A virus, as measured by decreased viral lung titers, inhibition of mass loss, and increased survival.
Ulmer
J B
JB
Department of Cancer Research, Merck Research Laboratories, West Point, PA 19486.
Donnelly
J J
JJ
Parker
S E
SE
Rhodes
G H
GH
Felgner
P L
PL
Dwarki
V J
VJ
Gromkowski
S H
SH
Deck
R R
RR
DeWitt
C M
CM
Friedman
A
A
D000818:Animals; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics* / Q000627:therapeutic use; D015870:Gene Expression; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007114:Immunization; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000235:genetics* / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000382:microbiology / Q000517:prevention & control*; D010957:Plasmids; D016601:RNA-Binding Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014758:Viral Core Proteins / Q000235:genetics* / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics*
D004279:DNA, Viral; D015395:Histocompatibility Antigens Class I; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D014765:Viral Vaccines