Effective construction of DNA vaccines against variable influenza genes by homologous recombination.
We demonstrate the potential of cloning by homologous recombination as a rapid method to construct DNA molecules encoding newly developing hemagglutinins (HA) of influenza A virus. The variable parts of the HA genes were cloned into a basic construct containing the HA gene from an H3N2 strain. The recombinant DNAs thus created encode different variable domains with neutralising epitopes from four recently circulating influenza A H3 strains. The technology allows rapid production of DNA constructs for vaccines that can induce antibody and, particularly, cellular immune responses. These new constructs were also capable of conferring protection to challenge in mice. The technology may hence be a valuable tool for rapid adaptation of influenza vaccines to changes in the circulating influenza strains.
Ljungberg
K
K
Swedish Institute for Infectious Disease Control, Karolinska Institute, Stockholm, SE-171 82. Karl.Ljungberg.smi.ki.se
Wahren
B
B
Almqvist
J
J
Hinkula
J
J
Linde
A
A
Winberg
G
G
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004285:Dogs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000235:genetics* / Q000276:immunology; D007251:Influenza, Human / Q000235:genetics* / Q000276:immunology*; D008251:Macaca; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics; D011995:Recombination, Genetic; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000235:genetics* / Q000276:immunology
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA