Influenza as Vaccine Carrier for HIV, TB
Influenza virus is an excellent carrier for foreign epitopes. At Polymun vaccine candidates were constructed for HIV and tuberculosis (TB).
Polymun uses the nasal spray influenza system also as carrier for foreign antigens to the immune system. For that purpose Polymun has established functional techniques and selection systems (using the interferon deficient Vero cell line) to engineer and to introduce large foreign gene sequences into the NS1 gene of influenza. As a model we inserted a functional green fluorescence protein (GFP).HIV
Based on our technology Polymun has engineered various HIV-gene segments into its flu-vectors and used them for nasal spray immunization. Promising cellular and humoral immune response in the murine model was obtained.
TB
The ESAT-6 antigen from mycobacterium tuberculosis was introduced into the NS1 gene of influenza A. In the mouse model these vaccine candidates were compared with the currently used BCG vaccine. Challenging the animals with the mouse pathogenic strain mycobacterium bovis displayed significantly improved protection compared to the BCG vaccine.
Polymun is looking for an investor who wants to continue with this technology.
Patents:
Recombinant influenza A virusesgranted by: AU 2001250352; EP 1 259 629 (AT BE CH/LI DE FR GB IT NL); RU 2280690; US 6,800,288
pending in: international stage WO0164860
Live vaccine and method of manufacture
granted by: AU 2002223560; CN ZL01819206.8; EP 1 358 319 (AT BE CH/LI CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE SI TR); US 7,494,659
pending in: CA, JP, KR
Publications:
Ferko B, Kittel C, Romanova J, Sereinig S, Katinger H, Egorov A (2006) Live attenuated influenza virus expressing human interleukin-2 reveals increased immunogenic potential in young and aged hosts. J Virol 80(23):11621-7Sereinig S, Stukova M, Zabolotnyh N, Ferko B, Kittel C, Romanova J, Vinogradova T, Katinger H, Kiselev O, Egorov A (2006) Influenza virus NS vectors expressing the mycobacterium tuberculosis ESAT-6 protein induce CD4+ Th1 immune response and protect animals against tuberculosis challenge. Clin Vaccine Immunol 13(8):898-904
Stukova MA, Sereinig S, Zabolotnyh NV, Ferko B, Kittel C, Romanova J, Vinogradova TI, Katinger H, Kiselev OI, Egorov A (2006) Vaccine potential of influenza vectors expressing Mycobacterium tuberculosis ESAT-6 protein. Tuberculosis 86(3-4):236-46
Kittel C, Ferko B, Kurz M, Voglauer R, Sereinig S, Romanova J, Stiegler G, Katinger H, Egorov A (2005) Generation of an influenza A virus vector expressing biologically active human interleukin-2 from the NS gene segment. J Virol 79(16):10672-7
Kittel C, Sereinig S, Ferko B, Stasakova J, Romanova J, Wolkerstorfer A, Katinger H, Egorov A (2004) Rescue of influenza virus expressing GFP from the NS1 reading frame. Virology 324(1):67-73
Poomputsa K, Kittel C, Egorov A, Ernst W, Grabherr R (2003) Generation of recombinant influenza virus using baculovirus delivery vector. J Virol Methods 110(1):111-4
Ferko B, Stasakova J, Sereinig S, Romanova J, Katinger D, Niebler B, Katinger H, Egorov A (2001) Hyperattenuated recombinant influenza A virus nonstructural-protein-encoding vectors induce human immunodeficiency virus type 1 Nef-specific systemic and mucosal immune responses in mice. J Virol 75(19):8899-908
Garcia-Sastre A, Egorov A, Matassov D, Brandt S, Levy DE, Durbin JE, Palese P, Muster T (1998) Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252(2):324-30
Ferko B, Katinger D, Grassauer A, Egorov A, Romanova J, Niebler B, Katinger H, Muster T (1998) Chimeric influenza virus replicating predominantly in the murine upper respiratory tract induces local immune responses against human immunodeficiency virus type 1 in the genital tract. J Infect Dis 178(5):1359-68
Egorov A, Brandt S, Sereinig S, Romanova J, Ferko B, Katinger D, Grassauer A, Alexandrova G, Katinger H, Muster T (1998) Transfectant influenza A viruses with long deletions in the NS1 protein grow efficiently in Vero cells. J Virol 72(8):6437-41