Protective immunity against influenza A virus induced by immunization with DNA plasmid containing influenza M gene.
DNA vaccination is characterized by its preferential induction of the cytotoxic T cell lymphocyte (CTL) response and is expected to be a useful means of protection against viral infection. We examined the protective effect of an expression plasmid (pME18S-M) containing M1 and M2 genes of influenza A/PR/8/34. We detected the CTL activity by introducing these plasmids into BALB/c mice by either the intramuscular or the intranasal route. The influenza-specific antibody response was also induced, although its neutralizing effect against influenza virus was not observed. From 70 to 80% protection was observed in the mice immunized with the pME18S-M plasmid followed by lethal infection with influenza viruses of the A/WSN/33 and A/PR/8/34 strains, whereas all mice without the plasmid vaccination failed to survive. This protective activity was significantly weakened when the CD8(+) cells of these immunized mice were eliminated by several injections of anti-CD8 antibody. The protective activity was also weakened when anti-CD4 antibody was injected in the early phase of DNA vaccination. These data suggest that the pME18S-M plasmid is useful as a DNA vaccine for overcoming highly mutational influenza viruses.
Okuda
K
K
Department of Bacteriology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. kokuda@med.yokohama-cu.ac.jp
Ihata
A
A
Watabe
S
S
Okada
E
E
Yamakawa
T
T
Hamajima
K
K
Yang
J
J
Ishii
N
N
Nakazawa
M
M
Okuda
K
K
Ohnari
K
K
Nakajima
K
K
Xin
K Q
KQ
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004279:DNA, Viral / Q000008:administration & dosage / Q000276:immunology; D004285:Dogs; D009980:Influenza A virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000517:prevention & control*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D014763:Viral Matrix Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*
D004279:DNA, Viral; D019444:Vaccines, DNA; D014763:Viral Matrix Proteins