Cross-clade protective immune responses of NS1-truncated live attenuated H5N1 avian influenza vaccines

Shi, Suhua; Chen, Sujuan; Han, Weizhou; Wu, Bozeng; Zhang, Xiaojian; Tang, Ying; Wang, Xiao; Zhu, Yinbiao; Peng, Daxin; Liu, Xiufan

doi:10.1016/j.vaccine.2015.11.045

Cited by 19 publications

(17 citation statements)

References 37 publications

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“…Currently, the compulsory vaccination programme has still been one of the major strategies to prevent and control HPAIV outbreaks in China (Shi et al, ). However, the H5NX viruses of the newly designated subclade 2.3.4.4 (WHO/OIE/FAO ) have become dominant across the world since 2014.…”

Section: Discussionmentioning

confidence: 99%

“…Based on the current antigenic, genetic and epidemiologic data, no new candidate influenza vaccine viruses have been proposed. Notably, the A/goose/Guangdong/1/1996‐PR8 (Re‐1, clade 0), A/chicken/Shanxi/2/2006‐PR8 (Re‐4, clade 2), A/duck/Anhui/1/2006‐PR8 (Re‐5, clade 2.3.4), A/duck/Guangdong/S1322/2010‐PR8 (Re‐6, subclade 2.3.2.1), A/chicken/Liaoning/S4092/2011‐PR8 (Re‐7, clade 7.2) and A/chicken/Guizhou/4/13‐PR8 (Re‐8, subclade 2.3.4.4) monovalent vaccines and/or the bivalent or trivalent vaccines have been developed in chronological order in China (Ministry, ; 2015b; ) to prevent and control the HPAIV outbreaks (Shi et al, ). In this study, we analysed the antigenic variation of the H5 viruses between subclades 2.3.4.4 and 2.3.4, and explored the molecular basis for the antigenic variation by a comparative study of a series of HA mutants through reverse genetics.…”

Section: Introductionmentioning

confidence: 99%

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Amino acid substitutions in antigenic region B of hemagglutinin play a critical role in the antigenic drift of subclade 2.3.4.4 highly pathogenic H5NX influenza viruses

Liu

et al. 2019

Transbound Emerg Dis

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As one of the important control strategies for highly pathogenic avian influenza (HPAI) in China, vaccination has been implemented compulsively in poultry flocks since 2004. However, the emergence and dominance of the circulating antigenic variants require the update of vaccines periodically. In order to investigate the key molecular sites responsible for the antigenic drift, a total of 13 amino acid positions divergent between clade 2.3.4 H5 viruses and their descendent subclade 2.3.4.4 variants in or around the recognized antigenic epitopes A–E were initially identified through inspecting a comprehensive HA sequence alignment of the H5 subtype HPAI viruses. Subsequently, a panel of single‐site or multi‐site HA mutants was constructed by reverse genetics with two H5N1 viruses of S (clade 2.3.4) and QD1 (subclade 2.3.4.4) as the HA backbone to study their antigenic variations, respectively. The hemagglutination–inhibition assay revealed an evident impact of mutations at sites 88, 156, 205, 208, 239 and 289 to the HA antigenicity and highlighted that the amino acid substitutions located in the antigenic region B, especially the combined mutations at sites 205 and 208, were the major antigenic determinant which was also consistent with results from flow cytometry and antigenic mapping. Our findings provided more insights into the molecular mechanism of antigenic drift of the H5 subtype HPAI virus, which would be helpful for the selection of vaccine candidates and accordingly for the prevention and control of this devastating viral agent.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Amino acid substitutions in antigenic region B of hemagglutinin play a critical role in the antigenic drift of subclade 2.3.4.4 highly pathogenic H5NX influenza viruses

Liu

et al. 2019

Transbound Emerg Dis

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“…Several experimental LAIVs for birds, pigs, and horses have been constructed with NS1 protein truncations (Quinlivan et al, 2005; Vincent et al, 2007; Wang et al, 2008; Hyesun et al, 2016; Shi et al, 2016). Here we generated three NS1 mutant viruses (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128) by creating C-terminal NS1 truncations.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses

et al. 2017

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H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128) were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14, and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.

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“…The live attenuated influenza virus (LAIV) vaccine strategy additionally represents an equally promising means for pandemic vaccination as the use of inactivated vaccines since live viruses induce strong immune responses in unprimed populations, potentially allowing for the use of low doses. LAIV vaccine candidates are currently developed using nonreplicating or temperature-sensitive mutant viruses and have been tested in mice, ferrets, chickens, and African green monkeys, as well as in clinical studies in humans (43)(44)(45)(46). It is reported that the LAIV vaccine exhibits cross-protection between various clades of the H5N1 virus and broad protection against homologous and heterosubtypic viruses.…”

Section: Discussionmentioning

confidence: 99%

Generation of a Genetically Stable High-Fidelity Influenza Vaccine Strain

Naito

Mori

Ushirogawa

et al. 2017

J Virol

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Vaccination is considered the most effective preventive means for influenza control. The development of a master virus with high growth and genetic stability, which may be used for the preparation of vaccine viruses by gene reassortment, is crucial for the enhancement of vaccine performance and efficiency of production. Here, we describe the generation of a high-fidelity and high-growth influenza vaccine master virus strain with a single V43I amino acid change in the PB1 polymerase of the high-growth A/Puerto Rico/8/1934 (PR8) master virus. The PB1-V43I mutation was introduced to increase replication fidelity in order to design an H1N1 vaccine strain with a low error rate. The PR8-PB1-V43I virus exhibited good replication compared with that of the parent PR8 virus. In order to compare the efficiency of egg adaptation and the occurrence of gene mutations leading to antigenic alterations, we constructed 6:2 genetic reassortant viruses between the A(H1N1)pdm09 and the PR8-PB1-V43I viruses; hemagglutinin (HA) and neuraminidase (NA) were from the A(H1N1)pdm09 virus, and the other genes were from the PR8 virus. Mutations responsible for egg adaptation mutations occurred in the HA of the PB1-V43I reassortant virus during serial egg passages; however, in contrast, antigenic mutations were introduced into the HA gene of the 6:2 reassortant virus possessing the wild-type PB1. This study shows that the mutant PR8 virus possessing the PB1 polymerase with the V43I substitution may be utilized as a master virus for the generation of high-growth vaccine viruses with high polymerase fidelity, low error rates of gene replication, and reduced antigenic diversity during virus propagation in eggs for vaccine production.IMPORTANCE Vaccination represents the most effective prophylactic option against influenza. The threat of emergence of influenza pandemics necessitates the ability to generate vaccine viruses rapidly. However, as the influenza virus exhibits a high mutation rate, vaccines must be updated to ensure a good match of the HA and NA antigens between the vaccine and the circulating strain. Here, we generated a genetically stable master virus of the A/Puerto Rico/8/1934 (H1N1) backbone encoding an engineered high-fidelity viral polymerase. Importantly, following the application of the high-fidelity PR8 backbone, no mutation resulting in antigenic change was introduced into the HA gene during propagation of the A(H1N1)pdm09 candidate vaccine virus. The low error rate of the present vaccine virus should decrease the risk of generating mutant viruses with increased virulence. Therefore, our findings are expected to be useful for the development of prepandemic vaccines and live attenuated vaccines with higher safety than that of the present candidate vaccines.

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Cross-clade protective immune responses of NS1-truncated live attenuated H5N1 avian influenza vaccines

Cited by 19 publications

References 37 publications

Amino acid substitutions in antigenic region B of hemagglutinin play a critical role in the antigenic drift of subclade 2.3.4.4 highly pathogenic H5NX influenza viruses

Amino acid substitutions in antigenic region B of hemagglutinin play a critical role in the antigenic drift of subclade 2.3.4.4 highly pathogenic H5NX influenza viruses

Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses

Generation of a Genetically Stable High-Fidelity Influenza Vaccine Strain

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