Generation of candidate human influenza vaccine strains in cell culture - rehearsing the European response to an H7N1 pandemic threat.
BACKGROUND
Although H5N1 avian influenza viruses pose the most obvious imminent pandemic threat, there have been several recent zoonotic incidents involving transmission of H7 viruses to humans. Vaccines are the primary public health defense against pandemics, but reliance on embryonated chickens eggs to propagate vaccine and logistic problems posed by the use of new technology may slow our ability to respond rapidly in a pandemic situation.


OBJECTIVE
We sought to generate an H7 candidate vaccine virus suitable for administration to humans whose generation and amplification avoided the use of eggs.


METHODS
We generated a suitable H7 vaccine virus by reverse genetics. This virus, known as RD3, comprises the internal genes of A/Puerto Rico/8/34 with surface antigens of the highly pathogenic avian strain A/Chicken/Italy/13474/99 (H7N1). The multi-basic amino acid site in the HA gene, associated with high pathogenicity in chickens, was removed.


RESULTS
The HA modification did not alter the antigenicity of the virus and the resultant single basic motif was stably retained following several passages in Vero and PER.C6 cells. RD3 was attenuated for growth in embryonated eggs, chickens, and ferrets. RD3 induced an antibody response in infected animals reactive against both the homologous virus and other H7 influenza viruses associated with recent infection by H7 viruses in humans.


CONCLUSIONS
This is the first report of a candidate H7 vaccine virus for use in humans generated by reverse genetics and propagated entirely in mammalian tissue culture. The vaccine has potential use against a wide range of H7 strains.
Whiteley
Alison
A
School of Biological Sciences, University of Reading, Reading, UK.
Major
Diane
D
Legastelois
Isabelle
I
Campitelli
Laura
L
Donatelli
Isabella
I
Thompson
Catherine I
CI
Zambon
Maria C
MC
Wood
John M
JM
Barclay
Wendy S
WS
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001483:Base Sequence; D002460:Cell Line; D002642:Chick Embryo; D004279:DNA, Viral / Q000235:genetics; D004196:Disease Outbreaks / Q000517:prevention & control; D005060:Europe / Q000453:epidemiology; D005260:Female; D005289:Ferrets; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D016865:Reassortant Viruses / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics
D000914:Antibodies, Viral; D004279:DNA, Viral; D007252:Influenza Vaccines; D014764:Viral Proteins