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An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus.

Leung HC, Chan CC, Poon VK, Zhao HJ, Cheung CY, Ng F, Huang JD, Zheng BJ - Emerg Microbes Infect (2015)

Bottom Line: Since then, there have been 458 confirmed infection cases and 177 deaths.A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments.Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, University of Hong Kong , Hong Kong, China.

ABSTRACT
In March 2013, a patient infected with a novel avian influenza A H7N9 virus was reported in China. Since then, there have been 458 confirmed infection cases and 177 deaths. The virus contains several human-adapted markers, indicating that H7N9 has pandemic potential. The outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. Previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of the H5N1 virus (H5N1-M2e) could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection with the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20, and 21 between M2e of H5N1 and H7N9, H5N1-M2e vaccination with either Freund's adjuvant or the Sigma adjuvant system (SAS) induced a high level of anti-M2e antibody, which cross-reacted with H7N9-M2e peptide. A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of the H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections. Therefore, this vaccine may be an ideal candidate for developing a universal vaccine to prevent the reemergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus.

No MeSH data available.


Related in: MedlinePlus

The 3D structure prediction of the M2e structures of H5N1 and H7N9 subtypes. The 3D structures of M2e of (A) A/Vietnam/1194/04 (H5N1), (B) A/Anhui/01/13 (H7N9), (C) A/Hong Kong/156/97 (H5N1), and (D) A/Beijing/501/09 were predicted using the online software PEP-FOLD. The skeleton structure prediction model is shown on the left, and the amino acid spherical structure prediction model is shown on the right with two different angles. Each amino acid is shown with its specific color according to the software. The amino acid variations between A/Vietnam/1194/04 (H5N1), A/Anhui/01/13 (H7N9), A/Hong Kong/156/97 (H5N1), and A/Beijing/501/09 (H1N1) are indicated with white numbers on the skeleton prediction models.
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fig5: The 3D structure prediction of the M2e structures of H5N1 and H7N9 subtypes. The 3D structures of M2e of (A) A/Vietnam/1194/04 (H5N1), (B) A/Anhui/01/13 (H7N9), (C) A/Hong Kong/156/97 (H5N1), and (D) A/Beijing/501/09 were predicted using the online software PEP-FOLD. The skeleton structure prediction model is shown on the left, and the amino acid spherical structure prediction model is shown on the right with two different angles. Each amino acid is shown with its specific color according to the software. The amino acid variations between A/Vietnam/1194/04 (H5N1), A/Anhui/01/13 (H7N9), A/Hong Kong/156/97 (H5N1), and A/Beijing/501/09 (H1N1) are indicated with white numbers on the skeleton prediction models.

Mentions: We analyzed monomer sequences of H5N1-M2e (A/Vietnam/1194/04) and H7N9-M2e (A/Anhui/01/13) using PEP-FOLD and compared the structural differences between the predicted 3D models. M2e of A/Hong Kong/156/97 (H5N1), which is non-reactive with H5N1-M2e (A/Vietnam/1194/04) induced antibody,19 and M2e of A/Beijing/501/09 (H1N1), which is cross-reactive with H5N1-M2e-induced antibody,21 were included for analysis. As shown in Figure 5, all four M2e were folded as hairpin shapes. The U-shaped regions of M2e-A/Vietnam/1194/04 (H5N1), M2e-A/Anhui/01/13 (H7N9), and M2e-A/Beijing/501/09 (H1N1) were more exposed than that of M2e-A/Hong Kong/97 (H5N1). The structural differences between these four M2e peptides might be due to the properties of the substituted amino acids, and they might affect the antigenic site accessibility.


An H5N1-based matrix protein 2 ectodomain tetrameric peptide vaccine provides cross-protection against lethal infection with H7N9 influenza virus.

Leung HC, Chan CC, Poon VK, Zhao HJ, Cheung CY, Ng F, Huang JD, Zheng BJ - Emerg Microbes Infect (2015)

The 3D structure prediction of the M2e structures of H5N1 and H7N9 subtypes. The 3D structures of M2e of (A) A/Vietnam/1194/04 (H5N1), (B) A/Anhui/01/13 (H7N9), (C) A/Hong Kong/156/97 (H5N1), and (D) A/Beijing/501/09 were predicted using the online software PEP-FOLD. The skeleton structure prediction model is shown on the left, and the amino acid spherical structure prediction model is shown on the right with two different angles. Each amino acid is shown with its specific color according to the software. The amino acid variations between A/Vietnam/1194/04 (H5N1), A/Anhui/01/13 (H7N9), A/Hong Kong/156/97 (H5N1), and A/Beijing/501/09 (H1N1) are indicated with white numbers on the skeleton prediction models.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4417706&req=5

fig5: The 3D structure prediction of the M2e structures of H5N1 and H7N9 subtypes. The 3D structures of M2e of (A) A/Vietnam/1194/04 (H5N1), (B) A/Anhui/01/13 (H7N9), (C) A/Hong Kong/156/97 (H5N1), and (D) A/Beijing/501/09 were predicted using the online software PEP-FOLD. The skeleton structure prediction model is shown on the left, and the amino acid spherical structure prediction model is shown on the right with two different angles. Each amino acid is shown with its specific color according to the software. The amino acid variations between A/Vietnam/1194/04 (H5N1), A/Anhui/01/13 (H7N9), A/Hong Kong/156/97 (H5N1), and A/Beijing/501/09 (H1N1) are indicated with white numbers on the skeleton prediction models.
Mentions: We analyzed monomer sequences of H5N1-M2e (A/Vietnam/1194/04) and H7N9-M2e (A/Anhui/01/13) using PEP-FOLD and compared the structural differences between the predicted 3D models. M2e of A/Hong Kong/156/97 (H5N1), which is non-reactive with H5N1-M2e (A/Vietnam/1194/04) induced antibody,19 and M2e of A/Beijing/501/09 (H1N1), which is cross-reactive with H5N1-M2e-induced antibody,21 were included for analysis. As shown in Figure 5, all four M2e were folded as hairpin shapes. The U-shaped regions of M2e-A/Vietnam/1194/04 (H5N1), M2e-A/Anhui/01/13 (H7N9), and M2e-A/Beijing/501/09 (H1N1) were more exposed than that of M2e-A/Hong Kong/97 (H5N1). The structural differences between these four M2e peptides might be due to the properties of the substituted amino acids, and they might affect the antigenic site accessibility.

Bottom Line: Since then, there have been 458 confirmed infection cases and 177 deaths.A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments.Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, University of Hong Kong , Hong Kong, China.

ABSTRACT
In March 2013, a patient infected with a novel avian influenza A H7N9 virus was reported in China. Since then, there have been 458 confirmed infection cases and 177 deaths. The virus contains several human-adapted markers, indicating that H7N9 has pandemic potential. The outbreak of this new influenza virus highlighted the need for the development of universal influenza vaccines. Previously, we demonstrated that a tetrameric peptide vaccine based on the matrix protein 2 ectodomain (M2e) of the H5N1 virus (H5N1-M2e) could protect mice from lethal infection with different clades of H5N1 and 2009 pandemic H1N1 influenza viruses. In this study, we investigated the cross-protection of H5N1-M2e against lethal infection with the new H7N9 virus. Although five amino acid differences existed at positions 13, 14, 18, 20, and 21 between M2e of H5N1 and H7N9, H5N1-M2e vaccination with either Freund's adjuvant or the Sigma adjuvant system (SAS) induced a high level of anti-M2e antibody, which cross-reacted with H7N9-M2e peptide. A mouse-adapted H7N9 strain, A/Anhui/01/2013m, was used for lethal challenge in animal experiments. H5N1-M2e vaccination provided potent cross-protection against lethal challenge of the H7N9 virus. Reduced viral replication and histopathological damage of mouse lungs were also observed in the vaccinated mice. Our results suggest that the tetrameric H5N1-M2e peptide vaccine could protect against different subtypes of influenza virus infections. Therefore, this vaccine may be an ideal candidate for developing a universal vaccine to prevent the reemergence of avian influenza A H7N9 virus and the emergence of potential novel reassortants of influenza virus.

No MeSH data available.


Related in: MedlinePlus