tetano
Editor, Senior Moderator
Published ahead of print 13 March 2013, doi: 10.1128/JVI.00273-13
Identification of dominant ADCC epitopes on hemagglutinin antigen of pandemic H1N1 influenza virus
Vikram Srivastavaa,
Zheng Yanga,
Ivan Fan Ngai Hungb,
Jianqing Xuc,
Bojian Zhenga and
Mei-Yun Zhanga,1
+ Author Affiliations
aDepartment of Microbiology
bDepartment of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
cInstitutes of Biomedical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
ABSTRACT
Antibody-dependent cell-mediated cytotoxicity (ADCC) bridges innate and adaptive immunity, and it involves both humoral and cellular immune responses. ADCC has been found to be a main route of immune protection against viral infections in vivo. Haemagglutinin (HA) of influenza virus is highly immunogenic and considered the most important target for immune protection. Several potent cross-reactive HA-specific neutralizing monoclonal antibodies (mAbs) have been reported and their conserved neutralizing epitopes revealed, but there has been no report so far about ADCC epitopes on HA. Here we identified two dominant ADCC epitopes, designated E1 [Amino acid (AA) 92-117] and E2 (AA 124-159), on HA of pandemic H1N1 influenza virus by epitope mapping of convalescent plasma IgGs from six H1N1-infected human subjects in China that exhibited different levels of ADCC activity. E1 and E2 ADCC epitopes overlapped with immunodominant epitopes of HA. Depletion of purified patient plasma IgGs with yeast cells expressing E1 or E2 peptides decreased ADCC activity of the IgGs. E1 and E2 sequences were found to be highly conserved in H1N1 strains, but less so in other subtypes of influenza A viruses. Our study may aid in designing immunogens that can elicit antibodies with high ADCC activity. Vaccine immunogens designed to include the structural determinants of potent broadly neutralizing Abs and ADCC epitopes may confer a comprehensive immune protection against influenza virus infection.
http://jvi.asm.org/content/early/2013/03/07/JVI.00273-13.abstract
Identification of dominant ADCC epitopes on hemagglutinin antigen of pandemic H1N1 influenza virus
Vikram Srivastavaa,
Zheng Yanga,
Ivan Fan Ngai Hungb,
Jianqing Xuc,
Bojian Zhenga and
Mei-Yun Zhanga,1
+ Author Affiliations
aDepartment of Microbiology
bDepartment of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
cInstitutes of Biomedical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China
ABSTRACT
Antibody-dependent cell-mediated cytotoxicity (ADCC) bridges innate and adaptive immunity, and it involves both humoral and cellular immune responses. ADCC has been found to be a main route of immune protection against viral infections in vivo. Haemagglutinin (HA) of influenza virus is highly immunogenic and considered the most important target for immune protection. Several potent cross-reactive HA-specific neutralizing monoclonal antibodies (mAbs) have been reported and their conserved neutralizing epitopes revealed, but there has been no report so far about ADCC epitopes on HA. Here we identified two dominant ADCC epitopes, designated E1 [Amino acid (AA) 92-117] and E2 (AA 124-159), on HA of pandemic H1N1 influenza virus by epitope mapping of convalescent plasma IgGs from six H1N1-infected human subjects in China that exhibited different levels of ADCC activity. E1 and E2 ADCC epitopes overlapped with immunodominant epitopes of HA. Depletion of purified patient plasma IgGs with yeast cells expressing E1 or E2 peptides decreased ADCC activity of the IgGs. E1 and E2 sequences were found to be highly conserved in H1N1 strains, but less so in other subtypes of influenza A viruses. Our study may aid in designing immunogens that can elicit antibodies with high ADCC activity. Vaccine immunogens designed to include the structural determinants of potent broadly neutralizing Abs and ADCC epitopes may confer a comprehensive immune protection against influenza virus infection.
http://jvi.asm.org/content/early/2013/03/07/JVI.00273-13.abstract