tetano
Editor, Senior Moderator
Biotechnol J. 2013 Oct 23. doi: 10.1002/biot.201300225. [Epub ahead of print]
Egg- or cell culture-derived hemagglutinin mutations impair virus stability and antigen content of inactivated influenza vaccines.
Nakowitsch S, Waltenberger AM, Wressnigg N, Ferstl N, Triendl A, Kiefmann B, Montomoli E, Lapini G, Sergeeva M, Muster T, Romanova JR.
Source
Avir Green Hills Biotechnology AG, Vienna, Austria.
Abstract
Egg-derived viruses are the only available seed material for influenza vaccine production. Vaccine manufacturing is done in embryonated chicken eggs, MDCK or Vero cells. In order to contribute to efficient production of influenza vaccines, we investigate whether the quality of inactivated vaccines is influenced by the propagation substrate. We demonstrate that H3N2 egg-derived seed viruses (A/Brisbane/10/07, IVR147, and A/Uruguay/716/07) triggered the hemagglutinin (HA) conformational change under less acidic conditions (0.2-0.6 pH units) than antigenically similar primary isolates. This phenotype was associated with HA1 (A138S, L194P) and HA2 (D160N) substitutions, and strongly related to decreased virus stability towards acidic pH and elevated temperature. The subsequent propagation of H3N2 and H1N1 egg-derived seed viruses in MDCK and Vero cells induced HA2 N50K (H1N1) and D160E (H3N2) mutations, improving virus growth in cell culture but further impairing virus stability. The prevention of the loss or recovery of stability was possible by cultivation at acidified conditions. Viruses carrying less stable HAs are more sensitive for HA conformational change during concentration, purification and storage. This results in decreased detectable HA antigen content - the main potency marker for inactivated influenza vaccines. Thus, virus stability can be a useful marker for predicting the manufacturing scope of seed viruses.
? 2013 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use and distribution in any medium, provided the original work is properly cited.
KEYWORDS:
Hemagglutinin antigen content, Inactivated vaccines, Influenza virus, Temperature stability, pH stability
PMID:
24323790
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24323790
Egg- or cell culture-derived hemagglutinin mutations impair virus stability and antigen content of inactivated influenza vaccines.
Nakowitsch S, Waltenberger AM, Wressnigg N, Ferstl N, Triendl A, Kiefmann B, Montomoli E, Lapini G, Sergeeva M, Muster T, Romanova JR.
Source
Avir Green Hills Biotechnology AG, Vienna, Austria.
Abstract
Egg-derived viruses are the only available seed material for influenza vaccine production. Vaccine manufacturing is done in embryonated chicken eggs, MDCK or Vero cells. In order to contribute to efficient production of influenza vaccines, we investigate whether the quality of inactivated vaccines is influenced by the propagation substrate. We demonstrate that H3N2 egg-derived seed viruses (A/Brisbane/10/07, IVR147, and A/Uruguay/716/07) triggered the hemagglutinin (HA) conformational change under less acidic conditions (0.2-0.6 pH units) than antigenically similar primary isolates. This phenotype was associated with HA1 (A138S, L194P) and HA2 (D160N) substitutions, and strongly related to decreased virus stability towards acidic pH and elevated temperature. The subsequent propagation of H3N2 and H1N1 egg-derived seed viruses in MDCK and Vero cells induced HA2 N50K (H1N1) and D160E (H3N2) mutations, improving virus growth in cell culture but further impairing virus stability. The prevention of the loss or recovery of stability was possible by cultivation at acidified conditions. Viruses carrying less stable HAs are more sensitive for HA conformational change during concentration, purification and storage. This results in decreased detectable HA antigen content - the main potency marker for inactivated influenza vaccines. Thus, virus stability can be a useful marker for predicting the manufacturing scope of seed viruses.
? 2013 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use and distribution in any medium, provided the original work is properly cited.
KEYWORDS:
Hemagglutinin antigen content, Inactivated vaccines, Influenza virus, Temperature stability, pH stability
PMID:
24323790
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24323790