Assessment of Influenza Virus Hemagglutinin Stalk-Based Immunity in Ferrets

被引：118

作者：

Krammer, Florian ^{[1
]}

Hai, Rong ^{[1
]}

Yondola, Mark ^{[1
]}

Tan, Gene S. ^{[1
]}

Leyva-Grado, Victor H. ^{[1
]}

Ryder, Alex B. ^{[2
]}

Miller, Matthew S. ^{[1
]}

Rose, John K. ^{[2
]}

Palese, Peter ^{[1
,3
]}

Garcia-Sastre, Adolfo ^{[1
,3
,4
]}

Albrecht, Randy A. ^{[1
,4
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[2] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA

[3] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA

[4] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY USA

来源：

JOURNAL OF VIROLOGY | 2014年 / 88卷 / 06期

基金：

奥地利科学基金会; 美国国家卫生研究院; 加拿大健康研究院;

关键词：

SEASONAL INFLUENZA; A VIRUS; PROTECTIVE IMMUNITY; HUMAN INFECTION; OSELTAMIVIR-RESISTANT; VACCINIA VIRUS; H3N2; VIRUS; H1N1; ANTIBODIES; NEURAMINIDASE;

D O I：

10.1128/JVI.03004-13

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Therapeutic monoclonal antibodies that target the conserved stalk domain of the influenza virus hemagglutinin and stalk-based universal influenza virus vaccine strategies are being developed as promising countermeasures for influenza virus infections. The pan-H1-reactive monoclonal antibody 6F12 has been extensively characterized and shows broad efficacy against divergent H1N1 strains in the mouse model. Here we demonstrate its efficacy against a pandemic HINI challenge virus in the ferret model of influenza disease. Furthermore, we recently developed a universal influenza virus vaccine strategy based on chimeric hemagglutinin constructs that focuses the immune response on the conserved stalk domain of the hemagglutinin. Here we set out to test this vaccination strategy in the ferret model. Both strategies, pretreatment of animals with a stalk-reactive monoclonal antibody and vaccination with chimeric hemagglutinin-based constructs, were able to significantly reduce viral titers in nasal turbinates, lungs, and olfactory bulbs. In addition, vaccinated animals also showed reduced nasal wash viral titers. In summary, both strategies showed efficacy in reducing viral loads after an influenza virus challenge in the ferret model.

引用

页码：3432 / 3442

页数：11

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