Recombinant Influenza Virus Vaccines

RECOMBINANT INFLUENZA VIRUS VACCINES

Influenza viruses type A, B and C cause flu in mammals and birds. The influenza virus type A has been the cause of several pandemics in the past, causing the deaths of millions of people. Its 13.6-kb genome consists of 8 ss linear RNA molecules that code for 11 proteins. Because of the segmented nature of its genome, alleles can easily be swapped between different influenza viruses strains during the co-infection of a host. This makes the virus extremely adaptable and able to escape the immune system by rapidly acquiring novel combinations of its immunogenic proteins. Two of these proteins are located on the surface of the viral particles and define their antigenicity: a hemagglutinin (H or HA) and a neuraminidase (N or NA). To date there are 16 different H antigens (H1–H16) and 9 different N antigens (N1–N9) known, thus the influenza A viruses are classified accordingly as H1N1 (swine flu or Spanish flu), H5N1 (bird flu), H7N7 (horse flu), etc. Seasonal flu recurs annually and since 2003 it has been caused mostly by variants of the H3N2, types is constantly being monitored with the aim of anticipating the serotype composition of potential pandemic influenza viruses. Because of the short time frame between the identification of a novel strain and the need for a vaccine against it, recombinant biotechnology is essential. As the hemagglutinin is the most rapidly evolving gene product and is crucial for viral attachment and evasion from the immune system recombinant influenza virus vaccines are developed using the gene coding this protein. To achieve this, the RNA is first converted into ds cDNA, cloned and sequenced. This allows the complete identification and genotyping of the virus. Secondly, the gene coding for the hemagglutinin is subcloned into a bacmid expression vector and the recombinant glycoprotein (rHA) is produced in large quantities by transfecting Spodoptera frugiperda insect cells growing in fermenters as for the hepatitis B vaccine.