Development of a new candidate H5N1 avian influenza virus for pre-pandemic vaccine production

BACKGROUND: Highly pathogenic H5N1 avian influenza viruses currently circulating in birds have caused hundreds of human infections, and pose a significant pandemic threat. Vaccines are a major component of the public health preparedness for this likely event. The rapid evolution of H5N1 viruses has resulted in the emergence of multiple clades with distinct antigenic characteristics that require clade-specific vaccines. A variant H5N1 virus termed clade 2.3.4 emerged in 2005 and has caused multiple fatal infections. Vaccine candidates that match the antigenic properties of variant viruses are necessary because inactivated influenza vaccines elicit strain-specific protection.

OBJECTIVE: To address the need for a suitable seed for manufacturing a clade 2.3.4 vaccine, we developed a new H5N1 pre-pandemic candidate vaccine by reverse genetics and evaluated its safety and replication in vitro and in vivo.

METHODS: A reassortant virus termed, Anhui/PR8, was produced by reverse genetics in compliance with WHO pandemic vaccine development guidelines and contains six genes from A/Puerto Rico/8/34 as well as the neuraminidase and hemagglutinin (HA) genomic segments from the A/Anhui/01/2005 virus. The multi-basic cleavage site of HA was removed to reduce virulence.

RESULTS: The reassortant Anhui/PR8 grows well in eggs and is avirulent to chicken and ferrets but retains the antigenicity of the parental A/Anhui/01/2005 virus.

CONCLUSION: These results indicate that the Anhui/PR8 reassortant lost a major virulent determinant and it is suitable for its use in vaccine manufacturing and as a reference vaccine virus against the H5N1 clade 2.3.4 viruses circulating in eastern China, Vietnam, Thailand, and Laos.

Medienart:

E-Artikel

Erscheinungsjahr:

2009

Erschienen:

2009

Enthalten in:

Zur Gesamtaufnahme - volume:3

Enthalten in:

Influenza and other respiratory viruses - 3(2009), 6 vom: 01. Nov., Seite 287-95

Sprache:

Englisch

Beteiligte Personen:

Dong, Jie [VerfasserIn]
Matsuoka, Yumiko [VerfasserIn]
Maines, Taronna R [VerfasserIn]
Swayne, David E [VerfasserIn]
O'Neill, Eduardo [VerfasserIn]
Davis, C Todd [VerfasserIn]
Van-Hoven, Neal [VerfasserIn]
Balish, Amanda [VerfasserIn]
Yu, Hong-jie [VerfasserIn]
Katz, Jacqueline M [VerfasserIn]
Klimov, Alexander [VerfasserIn]
Cox, Nancy [VerfasserIn]
Li, De-xin [VerfasserIn]
Wang, Yu [VerfasserIn]
Guo, Yuan-ji [VerfasserIn]
Yang, Wei-zhong [VerfasserIn]
Donis, Ruben O [VerfasserIn]
Shu, Yue-long [VerfasserIn]

Links:

Volltext

Themen:

Antibodies, Viral
Influenza Vaccines
Journal Article
RNA, Viral
Vaccines, Attenuated
Vaccines, Synthetic

Anmerkungen:

Date Completed 07.01.2010

Date Revised 20.10.2021

published: Print

Citation Status MEDLINE

doi:

10.1111/j.1750-2659.2009.00104.x

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM19273721X