Live attenuated influenza A/Vietnam/1203/04 (H5N1) (VN04 cold adapted [ca]) and A/Hong Kong/213/03 (H5N1) (HK03 ca) vaccine viruses were compared with the A/New Caledonia/20/99 (H1N1) (NC99 ca) seasonal vaccine virus for induction of host gene expression in infected human epithelial cells. Levels of proinflammatory cytokines and interferon-related genes were significantly upregulated in VN04 ca virus-infected A549 cells compared to cells infected with the HK03 ca and NC99 ca viruses as examined by microarray analysis and confirmed by quantitative RT-PCR and ELISA assays. Further mapping studies demonstrated that the hemagglutinin (HA) protein of the VN04 ca virus contributed to the hyperinduction of cytokines. The inactivated viruses could also induce the production of the cytokines and chemokines, albeit at a much lower level than live viruses. Compared to HK03 ca virus, VN04 ca virus differs by 9 amino acids including an additional glycosylation site at residue 158N of the HA protein and a shortened stalk in the neuraminidase (NA) protein. Increased cytokine production by HK03 ca virus was only observed when HK03 ca virus acquired an additional glycosylation in the HA protein and when its NA protein was replaced by that of VN04. Thus, our data indicate that the HA protein and its interaction with the NA protein play a role in triggering cytokine responses. The full implications of cytokine induction in vaccine virus-induced immune responses remain to be explored.
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http://dx.doi.org/10.1016/j.virol.2010.06.048 | DOI Listing |
PLoS One
October 2011
MedImmune, Mountain View, California, United States of America.
Priming immunization plays a key role in protecting individuals or populations to influenza viruses that are novel to humans. To identify the most promising vaccine priming strategy, we have evaluated different prime-boost regimens using inactivated, DNA and live attenuated vaccines in ferrets. Live attenuated influenza A/Vietnam/1203/2004 (H5N1) candidate vaccine (LAIV, VN04 ca) primed ferrets efficiently while inactivated H5N1 vaccine could not prime the immune response in seronegative ferrets unless an adjuvant was used.
View Article and Find Full Text PDFVirology
October 2010
Medimmune, 319 North Bernardo Avenue, Mountain View, CA 93043, USA.
Live attenuated influenza A/Vietnam/1203/04 (H5N1) (VN04 cold adapted [ca]) and A/Hong Kong/213/03 (H5N1) (HK03 ca) vaccine viruses were compared with the A/New Caledonia/20/99 (H1N1) (NC99 ca) seasonal vaccine virus for induction of host gene expression in infected human epithelial cells. Levels of proinflammatory cytokines and interferon-related genes were significantly upregulated in VN04 ca virus-infected A549 cells compared to cells infected with the HK03 ca and NC99 ca viruses as examined by microarray analysis and confirmed by quantitative RT-PCR and ELISA assays. Further mapping studies demonstrated that the hemagglutinin (HA) protein of the VN04 ca virus contributed to the hyperinduction of cytokines.
View Article and Find Full Text PDFJ Virol
July 2010
MedImmune, 319 North Bernardo Ave., Mountain View, CA 94043, USA.
A live attenuated influenza A/Vietnam/1203/2004 (H5N1) vaccine virus (VN04 ca) has receptor binding specificity to alpha2,3-linked sialosides (alpha2,3SAL), and a single dose induces a minimal serum antibody response in mice and ferrets. In contrast, A/Hong Kong/213/2003 (H5N1) vaccine virus (HK03 ca) binds to both alpha2,6SAL and alpha2,3SAL and generates a stronger serum antibody response in animals. Among the 9 amino acids that differed between the two H5 HA1 proteins, several HK03-specific residues enabled the VN04 ca virus to bind to both alpha2,3SAL and alpha2,6SAL receptors, but only the removal of the 158N glycosylation, together with an S227N change, resulted in more-efficient viral replication in the upper respiratory tract of ferrets and an increased serum antibody response.
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