Giuseppe
Emeritus
[Source: PLoS ONE, full page: (LINK). Abstract, edited.]
Research Article
Evaluation of Live Attenuated H7N3 and H7N7 Vaccine Viruses for Their Receptor Binding Preferences, Immunogenicity in Ferrets and Cross Reactivity to the Novel H7N9 Virus
Qi Xu, Zhongying Chen, Xing Cheng, Lucy Xu, Hong Jin
Abstract
Live attenuated influenza vaccine (LAIV) candidates of the H7 subtype, A/Netherlands/219/03 (H7N7, NL03 ca) and A/chicken/British Columbia/CN-6/2004 (H7N3, BC04 ca), were evaluated for their receptor binding specificity and immunogenicity in ferrets. The BC04 ca virus exhibited α2,3-SA and α2,6-SA dual receptor binding preference while the NL03 ca virus preferentially bound to α2,3-SA. Substitution of the Q226 and G228 (Q-G) by the L226 and S228 (L-S) residues in the HA improved binding to α2,6-SA for NL03 ca. The vaccine viruses with L-S retained the attenuation phenotype. NL03 L-S ca replicated more efficiently than the original NL03 ca virus in the upper respiratory tract of ferrets, and induced higher levels of humoral and cellular immune responses. Prior vaccination with seasonal LAIV reduced H7-specific antibody responses, but did not reduce the H7N7 vaccine mediated protection against a heterologous H7N3 BC04 wt virus infection in ferrets. In addition, the H7N3 and H7N7 vaccine immunized ferret sera cross reacted with the newly emerged H7N9 virus. These data, in combination with the safety data from previously conducted Phase 1 studies, suggest that these vaccines may have a role in responding to the threat posed by the H7N9 virus.
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Citation: Xu Q, Chen Z, Cheng X, Xu L, Jin H (2013) Evaluation of Live Attenuated H7N3 and H7N7 Vaccine Viruses for Their Receptor Binding Preferences, Immunogenicity in Ferrets and Cross Reactivity to the Novel H7N9 Virus. PLoS ONE 8(10): e76884. doi:10.1371/journal.pone.0076884
Editor: Shan Lu, University of Massachusetts Medical Center, United States of America
Received: May 28, 2013; Accepted: August 26, 2013; Published: October 9, 2013
Copyright: ? 2013 Xu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing interests: All authors are employees of MedImmune LLC. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
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Research Article
Evaluation of Live Attenuated H7N3 and H7N7 Vaccine Viruses for Their Receptor Binding Preferences, Immunogenicity in Ferrets and Cross Reactivity to the Novel H7N9 Virus
Qi Xu, Zhongying Chen, Xing Cheng, Lucy Xu, Hong Jin
Abstract
Live attenuated influenza vaccine (LAIV) candidates of the H7 subtype, A/Netherlands/219/03 (H7N7, NL03 ca) and A/chicken/British Columbia/CN-6/2004 (H7N3, BC04 ca), were evaluated for their receptor binding specificity and immunogenicity in ferrets. The BC04 ca virus exhibited α2,3-SA and α2,6-SA dual receptor binding preference while the NL03 ca virus preferentially bound to α2,3-SA. Substitution of the Q226 and G228 (Q-G) by the L226 and S228 (L-S) residues in the HA improved binding to α2,6-SA for NL03 ca. The vaccine viruses with L-S retained the attenuation phenotype. NL03 L-S ca replicated more efficiently than the original NL03 ca virus in the upper respiratory tract of ferrets, and induced higher levels of humoral and cellular immune responses. Prior vaccination with seasonal LAIV reduced H7-specific antibody responses, but did not reduce the H7N7 vaccine mediated protection against a heterologous H7N3 BC04 wt virus infection in ferrets. In addition, the H7N3 and H7N7 vaccine immunized ferret sera cross reacted with the newly emerged H7N9 virus. These data, in combination with the safety data from previously conducted Phase 1 studies, suggest that these vaccines may have a role in responding to the threat posed by the H7N9 virus.
_____
Citation: Xu Q, Chen Z, Cheng X, Xu L, Jin H (2013) Evaluation of Live Attenuated H7N3 and H7N7 Vaccine Viruses for Their Receptor Binding Preferences, Immunogenicity in Ferrets and Cross Reactivity to the Novel H7N9 Virus. PLoS ONE 8(10): e76884. doi:10.1371/journal.pone.0076884
Editor: Shan Lu, University of Massachusetts Medical Center, United States of America
Received: May 28, 2013; Accepted: August 26, 2013; Published: October 9, 2013
Copyright: ? 2013 Xu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing interests: All authors are employees of MedImmune LLC. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
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