tetano
Editor, Senior Moderator
J Virol. 2017 May 10. pii: JVI.00547-17. doi: 10.1128/JVI.00547-17. [Epub ahead of print]
[h=1]Development of clade-specific and broadly reactive live attenuated influenza virus vaccines against rapidly evolving H5 subtype viruses.[/h] Boonnak K[SUP]1[/SUP], Matsuoka Y[SUP]1[/SUP], Wang W[SUP]2[/SUP], Suguitan AL Jr[SUP]2[/SUP], Chen Z[SUP]2[/SUP], Paskel M[SUP]1[/SUP], Baz M[SUP]1[/SUP], Moore I[SUP]3[/SUP], Jin H[SUP]2[/SUP], Subbarao K[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] We have developed pandemic live attenuated influenza vaccines (pLAIV) against clade 1 H5N1 viruses on an Ann Arbor cold-adapted (ca) backbone that induced long-term immune memory. In 2015, many human infections caused by a new clade (2.2.1.1) of goose/Guangdong (gs/GD) lineage H5N1 viruses were reported in Egypt that prompted updating of the H5N1 pLAIV. We explored two strategies to generate suitable pLAIVs: first to modify the hemagglutinin gene of a highly pathogenic wild-type (wt) clade 2.2.1.1 virus A/Egypt/N03434/2009 (Egy/09) (H5N1) with its unmodified neuraminidase (NA) gene; this virus was designated Egy/09 ca The second approach was to select a low pathogenicity avian influenza H5 virus that elicited antibodies that cross-reacted with a broad range of H5 viruses, including the Egypt H5N1 viruses and contained a novel NA subtype for humans. We selected the low pathogenicity A/duck/Hokkaido/69/2000 (H5N3) virus (dk/Hok/00) for this purpose. Both candidate vaccines were attenuated and immunogenic in ferrets, inducing antibodies that neutralized homologous and heterologous H5 viruses with different degrees of cross-reactivity; Egy/09 ca vaccine antisera were more specific to the gs/GD lineage viruses but did not neutralize recent North American isolates (clade 2.3.4.4), whereas antisera from dk/Hok/69 ca vaccinated ferrets cross-reacted with clade 2.3.4.4 and 2.2.1 viruses but not clade 1 or 2.1 viruses. When vaccinated ferrets were challenged with homologous and heterologous H5 viruses, challenge virus replication was reduced in the respiratory tract. Thus, the two H5 pLAIV candidates are suitable for clinical development to protect humans from infection with different clades of H5 viruses.IMPORTANCE: In response to the continuing evolution of H5N1 avian influenza viruses and human infections, new candidate H5 live attenuated vaccines were developed using two different approaches: one targeted a specific circulating strain in Egypt and the other was based on a virus that elicits broadly cross-reactive antibodies against a wide range of H5 viruses. Both candidate vaccines were immunogenic and exhibited protective efficacy in ferrets. Our study permits a comparison of the two approaches and the data support further development of both vaccine viruses to optimally prepare for further spread of clade 2.2.1 or 2.3.4.4 viruses.
Copyright ? 2017 American Society for Microbiology.
PMID: 28490598 DOI: 10.1128/JVI.00547-17
[h=1]Development of clade-specific and broadly reactive live attenuated influenza virus vaccines against rapidly evolving H5 subtype viruses.[/h] Boonnak K[SUP]1[/SUP], Matsuoka Y[SUP]1[/SUP], Wang W[SUP]2[/SUP], Suguitan AL Jr[SUP]2[/SUP], Chen Z[SUP]2[/SUP], Paskel M[SUP]1[/SUP], Baz M[SUP]1[/SUP], Moore I[SUP]3[/SUP], Jin H[SUP]2[/SUP], Subbarao K[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] We have developed pandemic live attenuated influenza vaccines (pLAIV) against clade 1 H5N1 viruses on an Ann Arbor cold-adapted (ca) backbone that induced long-term immune memory. In 2015, many human infections caused by a new clade (2.2.1.1) of goose/Guangdong (gs/GD) lineage H5N1 viruses were reported in Egypt that prompted updating of the H5N1 pLAIV. We explored two strategies to generate suitable pLAIVs: first to modify the hemagglutinin gene of a highly pathogenic wild-type (wt) clade 2.2.1.1 virus A/Egypt/N03434/2009 (Egy/09) (H5N1) with its unmodified neuraminidase (NA) gene; this virus was designated Egy/09 ca The second approach was to select a low pathogenicity avian influenza H5 virus that elicited antibodies that cross-reacted with a broad range of H5 viruses, including the Egypt H5N1 viruses and contained a novel NA subtype for humans. We selected the low pathogenicity A/duck/Hokkaido/69/2000 (H5N3) virus (dk/Hok/00) for this purpose. Both candidate vaccines were attenuated and immunogenic in ferrets, inducing antibodies that neutralized homologous and heterologous H5 viruses with different degrees of cross-reactivity; Egy/09 ca vaccine antisera were more specific to the gs/GD lineage viruses but did not neutralize recent North American isolates (clade 2.3.4.4), whereas antisera from dk/Hok/69 ca vaccinated ferrets cross-reacted with clade 2.3.4.4 and 2.2.1 viruses but not clade 1 or 2.1 viruses. When vaccinated ferrets were challenged with homologous and heterologous H5 viruses, challenge virus replication was reduced in the respiratory tract. Thus, the two H5 pLAIV candidates are suitable for clinical development to protect humans from infection with different clades of H5 viruses.IMPORTANCE: In response to the continuing evolution of H5N1 avian influenza viruses and human infections, new candidate H5 live attenuated vaccines were developed using two different approaches: one targeted a specific circulating strain in Egypt and the other was based on a virus that elicits broadly cross-reactive antibodies against a wide range of H5 viruses. Both candidate vaccines were immunogenic and exhibited protective efficacy in ferrets. Our study permits a comparison of the two approaches and the data support further development of both vaccine viruses to optimally prepare for further spread of clade 2.2.1 or 2.3.4.4 viruses.
Copyright ? 2017 American Society for Microbiology.
PMID: 28490598 DOI: 10.1128/JVI.00547-17