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The Analysis of B-Cell Epitopes of Influenza Virus Hemagglutinin.

Shcherbinin DN, Alekseeva SV, Shmarov MM, Smirnov YA, Naroditskiy BS, Gintsburg AL - Acta Naturae (2016 Jan-Mar)

Bottom Line: Development of a vaccine with the new variants of HA acting as antigens takes a long time.In this paper, we tried to characterize the main B-cell epitopes of hemagglutinin and analyze our own and literature data on broadly neutralizing antibodies.The analysis showed that the core of the HA molecule, whose antibodies demonstrate pronounced heterosubtypic activity, can be used as a target for the search for and development of broad-spectrum antibodies to the influenza virus.

View Article: PubMed Central - PubMed

Affiliation: Federal State Budgetary Institution "Federal Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya" of the Ministry of Health of the Russian Federation, Gamaleya str. 18, Moscow, Russian Federation, 123098.

ABSTRACT
Vaccination has been successfully used to prevent influenza for a long time. Influenza virus hemagglutinin (HA), which induces a humoral immune response in humans and protection against the flu, is the main antigenic component of modern influenza vaccines. However, new seasonal and pandemic influenza virus variants with altered structures of HA occasionally occur. This allows the pathogen to avoid neutralization with antibodies produced in response to previous vaccination. Development of a vaccine with the new variants of HA acting as antigens takes a long time. Therefore, during an epidemic, it is important to have passive immunization agents to prevent and treat influenza, which can be monoclonal or single-domain antibodies with universal specificity (broad-spectrum agents). We considered antibodies to conserved epitopes of influenza virus antigens as universal ones. In this paper, we tried to characterize the main B-cell epitopes of hemagglutinin and analyze our own and literature data on broadly neutralizing antibodies. We conducted a computer analysis of the best known conformational epitopes of influenza virus HAs using materials of different databases. The analysis showed that the core of the HA molecule, whose antibodies demonstrate pronounced heterosubtypic activity, can be used as a target for the search for and development of broad-spectrum antibodies to the influenza virus.

No MeSH data available.


Related in: MedlinePlus

Schematic arrangement of B-cell epitopes in the amino acid sequence of hemagglutinin (HA). Thefigure was obtained using the Geneious 9.0.2 software as follows: the amino acid sequences ofinfluenza virus hemagglutinins recognized by the corresponding antibodies(Table 1) were alignedwith respect to each other. The epitope recognized by the corresponding antibody was mappedon each sequence. Information on the B-cell epitopes of HAs was obtained from the immunologicalepitope database. The figure in the middle shows HA with the following elements: HA1 and HA2chains (green), alpha helices (pink), antigenic sites: Cb (yellow), Ca1 (purple), Ca2 (blue), Sa (gray), and Sb (green).Location of B-cell epitopes of influenza A virus HA is shown above and below the HA(see Table 1). H1 (dark blue) andH3 (dark green) epitopes to the globular portion of HA are shown above; epitopes to the stem portion of HA (dark red)are shown below. Antigenic sites are mapped according to Caton A.J. [50].
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Figure 1: Schematic arrangement of B-cell epitopes in the amino acid sequence of hemagglutinin (HA). Thefigure was obtained using the Geneious 9.0.2 software as follows: the amino acid sequences ofinfluenza virus hemagglutinins recognized by the corresponding antibodies(Table 1) were alignedwith respect to each other. The epitope recognized by the corresponding antibody was mappedon each sequence. Information on the B-cell epitopes of HAs was obtained from the immunologicalepitope database. The figure in the middle shows HA with the following elements: HA1 and HA2chains (green), alpha helices (pink), antigenic sites: Cb (yellow), Ca1 (purple), Ca2 (blue), Sa (gray), and Sb (green).Location of B-cell epitopes of influenza A virus HA is shown above and below the HA(see Table 1). H1 (dark blue) andH3 (dark green) epitopes to the globular portion of HA are shown above; epitopes to the stem portion of HA (dark red)are shown below. Antigenic sites are mapped according to Caton A.J. [50].

Mentions: The largest amount of virus-neutralizing antibodies produced in a natural orartificial way bind to the globular portion of HA, resulting in blockage ofvirion binding to cells. However, since the HA gene rapidlymutates, new amino acid substitutions occur, leading to formation of newglycosylation sites, which in turn causes changes in the surface structure ofthe protein. Therefore, these antigenic sites are highly variable and thecorresponding antibodies are strain-specific. This partially explains whyimmunity after natural infection or vaccination is largely limited to thecirculating strain. For example, 2D1 antibodies binding to the Sa-antigenicsite located in the globular portion of the HA molecule recognize only thepandemic H1N1 viruses of 1918 and 2009, whose epitopes are antigenicallysimilar, although they are separated by almost a century[19]. Other H1 strains, such as PR8,cannot be recognized by these antibodies(Table 1),(Figure).


The Analysis of B-Cell Epitopes of Influenza Virus Hemagglutinin.

Shcherbinin DN, Alekseeva SV, Shmarov MM, Smirnov YA, Naroditskiy BS, Gintsburg AL - Acta Naturae (2016 Jan-Mar)

Schematic arrangement of B-cell epitopes in the amino acid sequence of hemagglutinin (HA). Thefigure was obtained using the Geneious 9.0.2 software as follows: the amino acid sequences ofinfluenza virus hemagglutinins recognized by the corresponding antibodies(Table 1) were alignedwith respect to each other. The epitope recognized by the corresponding antibody was mappedon each sequence. Information on the B-cell epitopes of HAs was obtained from the immunologicalepitope database. The figure in the middle shows HA with the following elements: HA1 and HA2chains (green), alpha helices (pink), antigenic sites: Cb (yellow), Ca1 (purple), Ca2 (blue), Sa (gray), and Sb (green).Location of B-cell epitopes of influenza A virus HA is shown above and below the HA(see Table 1). H1 (dark blue) andH3 (dark green) epitopes to the globular portion of HA are shown above; epitopes to the stem portion of HA (dark red)are shown below. Antigenic sites are mapped according to Caton A.J. [50].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837568&req=5

Figure 1: Schematic arrangement of B-cell epitopes in the amino acid sequence of hemagglutinin (HA). Thefigure was obtained using the Geneious 9.0.2 software as follows: the amino acid sequences ofinfluenza virus hemagglutinins recognized by the corresponding antibodies(Table 1) were alignedwith respect to each other. The epitope recognized by the corresponding antibody was mappedon each sequence. Information on the B-cell epitopes of HAs was obtained from the immunologicalepitope database. The figure in the middle shows HA with the following elements: HA1 and HA2chains (green), alpha helices (pink), antigenic sites: Cb (yellow), Ca1 (purple), Ca2 (blue), Sa (gray), and Sb (green).Location of B-cell epitopes of influenza A virus HA is shown above and below the HA(see Table 1). H1 (dark blue) andH3 (dark green) epitopes to the globular portion of HA are shown above; epitopes to the stem portion of HA (dark red)are shown below. Antigenic sites are mapped according to Caton A.J. [50].
Mentions: The largest amount of virus-neutralizing antibodies produced in a natural orartificial way bind to the globular portion of HA, resulting in blockage ofvirion binding to cells. However, since the HA gene rapidlymutates, new amino acid substitutions occur, leading to formation of newglycosylation sites, which in turn causes changes in the surface structure ofthe protein. Therefore, these antigenic sites are highly variable and thecorresponding antibodies are strain-specific. This partially explains whyimmunity after natural infection or vaccination is largely limited to thecirculating strain. For example, 2D1 antibodies binding to the Sa-antigenicsite located in the globular portion of the HA molecule recognize only thepandemic H1N1 viruses of 1918 and 2009, whose epitopes are antigenicallysimilar, although they are separated by almost a century[19]. Other H1 strains, such as PR8,cannot be recognized by these antibodies(Table 1),(Figure).

Bottom Line: Development of a vaccine with the new variants of HA acting as antigens takes a long time.In this paper, we tried to characterize the main B-cell epitopes of hemagglutinin and analyze our own and literature data on broadly neutralizing antibodies.The analysis showed that the core of the HA molecule, whose antibodies demonstrate pronounced heterosubtypic activity, can be used as a target for the search for and development of broad-spectrum antibodies to the influenza virus.

View Article: PubMed Central - PubMed

Affiliation: Federal State Budgetary Institution "Federal Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya" of the Ministry of Health of the Russian Federation, Gamaleya str. 18, Moscow, Russian Federation, 123098.

ABSTRACT
Vaccination has been successfully used to prevent influenza for a long time. Influenza virus hemagglutinin (HA), which induces a humoral immune response in humans and protection against the flu, is the main antigenic component of modern influenza vaccines. However, new seasonal and pandemic influenza virus variants with altered structures of HA occasionally occur. This allows the pathogen to avoid neutralization with antibodies produced in response to previous vaccination. Development of a vaccine with the new variants of HA acting as antigens takes a long time. Therefore, during an epidemic, it is important to have passive immunization agents to prevent and treat influenza, which can be monoclonal or single-domain antibodies with universal specificity (broad-spectrum agents). We considered antibodies to conserved epitopes of influenza virus antigens as universal ones. In this paper, we tried to characterize the main B-cell epitopes of hemagglutinin and analyze our own and literature data on broadly neutralizing antibodies. We conducted a computer analysis of the best known conformational epitopes of influenza virus HAs using materials of different databases. The analysis showed that the core of the HA molecule, whose antibodies demonstrate pronounced heterosubtypic activity, can be used as a target for the search for and development of broad-spectrum antibodies to the influenza virus.

No MeSH data available.


Related in: MedlinePlus