Plant-based rapid production of recombinant subunit hemagglutinin vaccines targeting H1N1 and H5N1 influenza.
In 2009, a novel H1N1 swine influenza virus was isolated from infected humans in Mexico and the United States, and rapidly spread around the world. Another virus, a highly pathogenic avian influenza virus of the H5N1 subtype, identified by the World Health Organization as a potential pandemic threat in 1997, continues to be a significant risk. While vaccination is the preferred strategy for the prevention and control of influenza infections, the traditional egg-based approach to producing influenza vaccines does not provide sufficient capacity and adequate speed to satisfy global needs to combat newly emerging strains, seasonal or potentially pandemic. Significant efforts are underway to develop and implement new cell substrates with improved efficiency for influenza vaccine development and manufacturing. In recent years, plants have been used to produce recombinant proteins including subunit vaccines and antibodies. The main advantages of using plant systems for the production of vaccine antigens against influenza are their independence from pathogenic viruses, and cost and time efficiency. Here, we describe the large-scale production of recombinant hemagglutinin proteins from A/California/04/09 (H1N1) and A/Indonesia/05/05 (H5N1) strains of influenza virus in Nicotiana benthamiana plants, and their immunogenicity (serum hemagglutination inhibition and virus neutralizing antibodies), and safety in animal models. These results support the testing of these candidate vaccines in human volunteers and also the utility of our plant expression system for large-scale recombinant influenza vaccine production.
Fraunhofer USA Center for Molecular Biotechnology, Newark, DE, USA.
Yoko
Y
Shoji
Jessica A
JA
Chichester
Mark
M
Jones
Slobodanka D
SD
Manceva
Emily
E
Damon
Vadim
V
Mett
Konstantin
K
Musiychuk
Hong
H
Bi
Christine
C
Farrance
Moneim
M
Shamloul
Natasha
N
Kushnir
Satish
S
Sharma
Vidadi
V
Yusibov
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001709:Biotechnology / Q000379:methods; D005289:Ferrets; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods; D014026:Nicotiana / Q000235:genetics; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic