Giuseppe
Emeritus
J Virol. 2009 Mar 11. [Epub ahead of print]
Non-replicating vaccinia vectors expressing the H5 influenza hemagglutinin produced in modified Vero cells induce robust protection.
Mayrhofer J, Coulibaly S, Hessel A, Holzer G, Schwendinger M, Br?hl P, Gerencer M, Crowe BA, Shuo S, Hong W, Tan YJ, Dietrich B, Sabarth N, Savidis-Dacho H, Kistner O, Barrett PN, Falkner FG. - Baxter Bioscience, Biomedical Research Center, Uferstrasse 15, A-2304 Orth/Donau, Austria; Collaborative Anti-Viral Research Group, Cancer and Developmental Cell Biology Division, Institute of Molecular and Cell Biology, A STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Singapore 138673.
The timely development of safe and effective vaccines against avian influenza of the H5N1 subtype will be of utmost importance in the event of a pandemic. Our aim was, first, to develop a safe live vaccine which induces both, humoral and cell-mediated immune responses against human H5N1 influenza viruses and, second - since the supply of embryonated eggs for traditional influenza vaccine production may be endangered in a pandemic - an egg-independent production procedure based on a permanent cell line.
In the present study, the generation of a complementing Vero cell line suitable for the production of safe poxviral vaccines is described. This cell line was used to produce a replication-deficient vaccinia vector H5N1 live vaccine, dVV-HA5, expressing the hemagglutinin of a virulent clade 1 H5N1 strain.
This experimental vaccine was compared with a formalin-inactivated whole virus vaccine based on the same clade and with different replicating poxvirus-vectored vaccines. Mice were immunized to assess protective immunity after high dose challenge with the highly virulent A/Vietnam/1203/2004(H5N1) strain.
A single dose of the defective live vaccine induced complete protection from lethal homologous virus challenge and also full cross-protection against clade 0 and 2 challenge viruses. Neutralizing antibody levels were comparable to those induced by the inactivated vaccine. Unlike the whole virus vaccine, the dVV-HA5 vaccine induced substantial amounts of interferon-gamma-secreting CD8 T cells.
Thus, the non-replicating recombinant vaccinia vectors are promising vaccine candidates that induce a broad immune response and can be produced in an egg-independent and adjuvant-independent manner in a proven vector system.
PMID: 19279103 [PubMed - as supplied by publisher]
-
-------
Non-replicating vaccinia vectors expressing the H5 influenza hemagglutinin produced in modified Vero cells induce robust protection.
Mayrhofer J, Coulibaly S, Hessel A, Holzer G, Schwendinger M, Br?hl P, Gerencer M, Crowe BA, Shuo S, Hong W, Tan YJ, Dietrich B, Sabarth N, Savidis-Dacho H, Kistner O, Barrett PN, Falkner FG. - Baxter Bioscience, Biomedical Research Center, Uferstrasse 15, A-2304 Orth/Donau, Austria; Collaborative Anti-Viral Research Group, Cancer and Developmental Cell Biology Division, Institute of Molecular and Cell Biology, A STAR (Agency for Science, Technology and Research), 61 Biopolis Drive, Singapore 138673.
The timely development of safe and effective vaccines against avian influenza of the H5N1 subtype will be of utmost importance in the event of a pandemic. Our aim was, first, to develop a safe live vaccine which induces both, humoral and cell-mediated immune responses against human H5N1 influenza viruses and, second - since the supply of embryonated eggs for traditional influenza vaccine production may be endangered in a pandemic - an egg-independent production procedure based on a permanent cell line.
In the present study, the generation of a complementing Vero cell line suitable for the production of safe poxviral vaccines is described. This cell line was used to produce a replication-deficient vaccinia vector H5N1 live vaccine, dVV-HA5, expressing the hemagglutinin of a virulent clade 1 H5N1 strain.
This experimental vaccine was compared with a formalin-inactivated whole virus vaccine based on the same clade and with different replicating poxvirus-vectored vaccines. Mice were immunized to assess protective immunity after high dose challenge with the highly virulent A/Vietnam/1203/2004(H5N1) strain.
A single dose of the defective live vaccine induced complete protection from lethal homologous virus challenge and also full cross-protection against clade 0 and 2 challenge viruses. Neutralizing antibody levels were comparable to those induced by the inactivated vaccine. Unlike the whole virus vaccine, the dVV-HA5 vaccine induced substantial amounts of interferon-gamma-secreting CD8 T cells.
Thus, the non-replicating recombinant vaccinia vectors are promising vaccine candidates that induce a broad immune response and can be produced in an egg-independent and adjuvant-independent manner in a proven vector system.
PMID: 19279103 [PubMed - as supplied by publisher]
-
-------