Influenza Vaccines Generated by Reverse Genetics

Author(s):  
K. Subbarao ◽  
J. M. Katz
2005 ◽  
Vol 79 (11) ◽  
pp. 6763-6771 ◽  
Author(s):  
Bin Lu ◽  
Helen Zhou ◽  
Dan Ye ◽  
George Kemble ◽  
Hong Jin

ABSTRACT The H3N2 influenza A/Fujian/411/02-like virus strains that circulated during the 2003-2004 influenza season caused influenza epidemics. Most of the A/Fujian/411/02 virus lineages did not replicate well in embryonated chicken eggs and had to be isolated originally by cell culture. The molecular basis for the poor replication of A/Fujian/411/02 virus was examined in this study by the reverse genetics technology. Two antigenically related strains that replicated well in embryonated chicken eggs, A/Sendai-H/F4962/02 and A/Wyoming/03/03, were compared with the prototype A/Fujian/411/02 virus. A/Sendai differed from A/Fujian by three amino acids in the neuraminidase (NA), whereas A/Wyoming differed from A/Fujian by five amino acids in the hemagglutinin (HA). The HA and NA segments of these three viruses were reassorted with cold-adapted A/Ann Arbor/6/60, the master donor virus for the live attenuated type A influenza vaccines (FluMist). The HA and NA residues differed between these three H3N2 viruses evaluated for their impact on virus replication in MDCK cells and in embryonated chicken eggs. It was determined that replication of A/Fujian/411/02 in eggs could be improved by either changing minimum of two HA residues (G186V and V226I) to increase the HA receptor-binding ability or by changing a minimum of two NA residues (E119Q and Q136K) to lower the NA enzymatic activity. Alternatively, recombinant A/Fujian/411/02 virus could be adapted to grow in eggs by two amino acid substitutions in the HA molecule (H183L and V226A), which also resulted in the increased HA receptor-binding activity. Thus, the balance between the HA and NA activities is critical for influenza virus replication in a different host system. The HA or NA changes that increased A/Fujian/411/02 virus replication in embryonated chicken eggs were found to have no significant impact on antigenicity of these recombinant viruses. This study demonstrated that the reverse genetics technology could be used to improve the manufacture of the influenza vaccines.


2012 ◽  
pp. 224-249 ◽  
Author(s):  
Ruth A. Elderfield ◽  
Lorian C. S. Hartgroves ◽  
Wendy S. Barclay

2005 ◽  
Vol 191 (8) ◽  
pp. 1216-1220 ◽  
Author(s):  
Aleksandr S. Lipatov ◽  
Richard J. Webby ◽  
Elena A. Govorkova ◽  
Scott Krauss ◽  
Robert G. Webster

The Lancet ◽  
2004 ◽  
Vol 363 (9415) ◽  
pp. 1099-1103 ◽  
Author(s):  
RJ Webby ◽  
DR Perez ◽  
JS Coleman ◽  
Y Guan ◽  
JH Knight ◽  
...  

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 190 ◽  
Author(s):  
Pilar Blanco-Lobo ◽  
Aitor Nogales ◽  
Laura Rodríguez ◽  
Luis Martínez-Sobrido

Influenza virus still represents a considerable threat to global public health, despite the advances in the development and wide use of influenza vaccines. Vaccination with traditional inactivate influenza vaccines (IIV) or live-attenuated influenza vaccines (LAIV) remains the main strategy in the control of annual seasonal epidemics, but it does not offer protection against new influenza viruses with pandemic potential, those that have shifted. Moreover, the continual antigenic drift of seasonal circulating influenza viruses, causing an antigenic mismatch that requires yearly reformulation of seasonal influenza vaccines, seriously compromises vaccine efficacy. Therefore, the quick optimization of vaccine production for seasonal influenza and the development of new vaccine approaches for pandemic viruses is still a challenge for the prevention of influenza infections. Moreover, recent reports have questioned the effectiveness of the current LAIV because of limited protection, mainly against the influenza A virus (IAV) component of the vaccine. Although the reasons for the poor protection efficacy of the LAIV have not yet been elucidated, researchers are encouraged to develop new vaccination approaches that overcome the limitations that are associated with the current LAIV. The discovery and implementation of plasmid-based reverse genetics has been a key advance in the rapid generation of recombinant attenuated influenza viruses that can be used for the development of new and most effective LAIV. In this review, we provide an update regarding the progress that has been made during the last five years in the development of new LAIV and the innovative ways that are being explored as alternatives to the currently licensed LAIV. The safety, immunogenicity, and protection efficacy profile of these new LAIVs reveal their possible implementation in combating influenza infections. However, efforts by vaccine companies and government agencies will be needed for controlled testing and approving, respectively, these new vaccine methodologies for the control of influenza infections.


2008 ◽  
Vol 130 (3-4) ◽  
pp. 268-276 ◽  
Author(s):  
Jae Min Song ◽  
Youn Jeong Lee ◽  
Ok Mi Jeong ◽  
Hyun Mi Kang ◽  
Hye Ryoung Kim ◽  
...  

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