Development of influenza A(H7N9) candidate vaccine viruses with improved hemagglutinin antigen yield in eggs

Influenza and Other Respiratory Viruses

Callie Ridenour²  Adam Johnson²  Emily Winne¹  Jaber Hossain²  Guaniri Mateu-Petit²  Amanda Balish²  Wanda Santana¹  Taejoong Kim²  Charles Davis²  Nancy J. Cox²  John R. Barr¹  Ruben O. Donis²  Julie Villanueva²  Tracie L. Williams¹ 

[1] Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA;Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA

关键词: Antigen yield;    H7N9;    hemagglutinin;    influenza;    serial passage;    vaccine;   

DOI  :  10.1111/irv.12322

来源: Wiley

【 摘 要 】

Abstract

Background

The emergence of avian influenza A(H7N9) virus in poultry causing zoonotic human infections was reported on March 31, 2013. Development of A(H7N9) candidate vaccine viruses (CVV) for pandemic preparedness purposes was initiated without delay. Candidate vaccine viruses were derived by reverse genetics using the internal genes of A/Puerto/Rico/8/34 (PR8). The resulting A(H7N9) CVVs needed improvement because they had titers and antigen yields that were suboptimal for vaccine manufacturing in eggs, especially in a pandemic situation.

Methods

Two CVVs derived by reverse genetics were serially passaged in embryonated eggs to improve the hemagglutinin (HA) antigen yield. The total viral protein and HA antigen yields of six egg-passaged CVVs were determined by the BCA assay and isotope dilution mass spectrometry (IDMS) analysis, respectively. CVVs were antigenically characterized by hemagglutination inhibition (HI) assays with ferret antisera.

Results

Improvement of total viral protein yield was observed for the six egg-passaged CVVs; HA quantification by IDMS indicated approximately a twofold increase in yield of several egg-passaged viruses as compared to that of the parental CVV. Several different amino acid substitutions were identified in the HA of all viruses after serial passage. However, HI tests indicated that the antigenic properties of two CVVs remained unchanged.

Conclusions

If influenza A(H7N9) viruses were to acquire sustained human-to-human transmissibility, the improved HA yield of the egg-passaged CVVs generated in this study could expedite vaccine manufacturing for pandemic mitigation.

【 授权许可】

CC BY   
Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.