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Modified Organism
Swine influenza virus vaccine
Record information and status
Record ID
115583
Status
Published
Date of creation
2020-05-08 21:24 UTC (austein.mcloughlin@cbd.int)
Date of publication
2020-05-08 21:24 UTC (austein.mcloughlin@cbd.int)

Living Modified Organism identity
The image below identifies the LMO through its unique identifier, trade name and a link to this page of the BCH. Click on it to download a larger image on your computer. For help on how to use it go to the LMO quick-links page.

LMO name
Swine influenza virus vaccine
Transformation event
H1N1 NS1
Developer(s)
Dra Patrícia Schwarz
technician in charge representing
Boheringer Ingelheim Química e Farmacêutica Ltda.
Avenida das Nações Unidas, 14171, 18º andar - Torre B - Vila Gertrudes. 04794-000.
São Paulo, São Paulo
Brazil, 04794-000
Phone:55 11 4949-4700
Fax:55 11 4949-4700
Email:simone_renata.farah@oheringer-ingelheim.com
Url:Boheringer Ingelheim
Description
The swine influenza vaccine is a bivalent vaccine containing two modified virions, H1N1 and H3N2, for developing immunity to both viruses. The modified H1N1 expresses H1N1 hemagglutinin (HA) and neuraminidase (NA), while the modified H3N2 expresses H3N2 HA and NA proteins. The other eight influenza proteins are from H3N2 for both modified virions. Attenuation was achieved by a truncation in the carboxy end of nonstructural protein 1. The vaccine was created through the transfection of eight plasmids corresponding to each viral genomic segment for each virus (separately). The fractions (H1N1 and H3N2) were later combined to create the vaccine.
Recipient Organism or Parental Organisms
The term Recipient organism refers to an organism (either already modified or non-modified) that was subjected to genetic modification, whereas Parental organisms refers to those that were involved in cross breeding or cell fusion.
Influenza A virus - Influenza, Flu, Avian flu, Human flu, Swine influenza, Equine influenza, Bird flu
Characteristics of the transformation process
Vector
plasmid pHW2000
Techniques used for the modification
  • plasmid-based transfection
Genetic elements construct
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Polymerase basic protein 2
2.33 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Polymerase basic protein 1
2.33 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Polymerase acidic protein
2.19 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Hemagglutinin gene
1.70 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Nucleoprotein
1.56 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Neuraminidase
1.41 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Matrix protein 2
0.03 Kb
 
 
Matrix protein 1
0.76 Kb
 
 
Matrix protein 2
0.27 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Nuclear export protein
0.03 Kb
 
 
Nonstructural protein 1
0.38 Kb
 
 
Nuclear export protein
0.34 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Polymerase basic protein 2
2.33 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Polymerase basic protein 1
2.33 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Polymerase acidic protein
2.19 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Hemagglutinin gene
1.76 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Nucleoprotein
1.56 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Neuraminidase
1.46 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Matrix protein 2
0.03 Kb
 
 
Matrix protein 1
0.76 Kb
 
 
Matrix protein 2
0.27 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
 
Human Cytomegalovirus promoter
0.35 Kb
 
 
Polymerase I terminator
0.03 Kb
 
 
Nuclear export protein
0.03 Kb
 
 
Nonstructural protein 1
0.38 Kb
 
 
Nuclear export protein
0.34 Kb
 
 
Human polymerase 1 promoter
0.23 Kb
 
 
Bovine growth hormone terminator
0.23 Kb
 
Further details
Notes regarding the genetic elements introduced or modified in this LMO
Transcription
Eight expression plasmids (pHW2000) corresponding to the viral genomic segments were transfected to express all influenza genes. The first eight genetic constructs above are for the H1N1 fraction and the later 8 are for the H3N2 fractions of the vaccine. The plasmid contains bidirectional sets of expression cassettes: Cytomegalovirus promoter - Bovine growth hormone terminator (sense) and Human polymerase I promoter - Mus musculus polymerase I terminator (antisense). The combination of transcription in both directions and interaction with host cellular machinery results in the production of infectious virions.

For protein expression of the influenza genes, transcription by RNA polymerase II is directed from the Cytomegalovirus promoter and terminates at the bovine hormone terminator. For segments VII and VII (matrix protein 2 and nuclear export protein, respectively), the transcripts will be spliced to join the initial coding sequences to the later sequences and form a mature mRNA. The transcripts receive 5' caps and 3' poly-adenylated tails. Thus, the transcripts are translated into proteins. To produce viral RNA to function as genomic material, transcription must produce negative sense (antisense) cRNA. Thus, transcription is directed from the human polymerase I promoter and terminates at the Mus musculus polymerase I terminator. These transcripts have a 5' triphosphate group and no polyadenylated tail. Thus, they are not translated into proteins.

Sequence source
H1N1 modified virion (Lot no. 241-192) - first eight genetic constructs above
Influenza strain A/swine/Minnesota/37866/1999 (H1N1): HA and NA proteins

Influenza strain A/Swine/Texas/4199-2/98 (H3N2): PB1, PB2, PA, NP, M1, M2, NS1 and NEP

H3N2 modified virion (Lot no. 241-196) - later eight genetic constructs above
Influenza strain A/Swine/Texas/4199-2/98 (H3N2): PB1, PB2, PA, HA, NP, NA, M1, M2, NS1 and NEP

Note:
For both modified virions, the nonstructural protein 1 (NS1) has been carboxyl-truncated and codes for amino acids 1 to 126 of the native protein. The truncation is related to the attenuation (reduction in virulence) of the seed virus.
LMO characteristics
Modified traits
Common use(s)
  • Vaccine