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Title: Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses


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Joyce, M.  Gordon, Wheatley, Adam K., Thomas, Paul V., Chuang, Gwo-Yu, Soto, Cinque, Bailer, Robert T., Druz, Aliaksandr, Georgiev, Ivelin S., Gillespie, Rebecca A., Kanekiyo, Masaru, Kong, Wing-Pui, Leung, Kwanyee, Narpala, Sandeep N., Prabhakaran, Madhu S., Yang, Eun Sung, Zhang, Baoshan, Zhang, Yi, Asokan, Mangaiarkarasi, Boyington, Jeffrey C., Bylund, Tatsiana, Darko, Sam, Lees, Christopher R., Ransier, Amy, Shen, Chen-Hsiang, Wang, Lingshu, Whittle, James R., Wu, Xueling, Yassine, Hadi M., Santos, Celia, Matsuoka, Yumiko, Tsybovsky, Yaroslav, Baxa, Ulrich, Mullikin, James C., Subbarao, Kanta, Douek, Daniel C., Graham, Barney S., Koup, Richard A., Ledgerwood, Julie E., Roederer, Mario, Shapiro, Lawrence, Kwong, Peter D., Mascola, John R., and McDermott, Adrian B. Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses. United States: N. p., 2016. Web. doi:10.1016/j.cell.2016.06.043.
Joyce, M.  Gordon, Wheatley, Adam K., Thomas, Paul V., Chuang, Gwo-Yu, Soto, Cinque, Bailer, Robert T., Druz, Aliaksandr, Georgiev, Ivelin S., Gillespie, Rebecca A., Kanekiyo, Masaru, Kong, Wing-Pui, Leung, Kwanyee, Narpala, Sandeep N., Prabhakaran, Madhu S., Yang, Eun Sung, Zhang, Baoshan, Zhang, Yi, Asokan, Mangaiarkarasi, Boyington, Jeffrey C., Bylund, Tatsiana, Darko, Sam, Lees, Christopher R., Ransier, Amy, Shen, Chen-Hsiang, Wang, Lingshu, Whittle, James R., Wu, Xueling, Yassine, Hadi M., Santos, Celia, Matsuoka, Yumiko, Tsybovsky, Yaroslav, Baxa, Ulrich, Mullikin, James C., Subbarao, Kanta, Douek, Daniel C., Graham, Barney S., Koup, Richard A., Ledgerwood, Julie E., Roederer, Mario, Shapiro, Lawrence, Kwong, Peter D., Mascola, John R., & McDermott, Adrian B. Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses. United States. doi:10.1016/j.cell.2016.06.043.
Joyce, M.  Gordon, Wheatley, Adam K., Thomas, Paul V., Chuang, Gwo-Yu, Soto, Cinque, Bailer, Robert T., Druz, Aliaksandr, Georgiev, Ivelin S., Gillespie, Rebecca A., Kanekiyo, Masaru, Kong, Wing-Pui, Leung, Kwanyee, Narpala, Sandeep N., Prabhakaran, Madhu S., Yang, Eun Sung, Zhang, Baoshan, Zhang, Yi, Asokan, Mangaiarkarasi, Boyington, Jeffrey C., Bylund, Tatsiana, Darko, Sam, Lees, Christopher R., Ransier, Amy, Shen, Chen-Hsiang, Wang, Lingshu, Whittle, James R., Wu, Xueling, Yassine, Hadi M., Santos, Celia, Matsuoka, Yumiko, Tsybovsky, Yaroslav, Baxa, Ulrich, Mullikin, James C., Subbarao, Kanta, Douek, Daniel C., Graham, Barney S., Koup, Richard A., Ledgerwood, Julie E., Roederer, Mario, Shapiro, Lawrence, Kwong, Peter D., Mascola, John R., and McDermott, Adrian B. 2016. "Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses". United States. doi:10.1016/j.cell.2016.06.043.
@article{osti_1314264,
title = {Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses},
author = {Joyce, M.  Gordon and Wheatley, Adam K. and Thomas, Paul V. and Chuang, Gwo-Yu and Soto, Cinque and Bailer, Robert T. and Druz, Aliaksandr and Georgiev, Ivelin S. and Gillespie, Rebecca A. and Kanekiyo, Masaru and Kong, Wing-Pui and Leung, Kwanyee and Narpala, Sandeep N. and Prabhakaran, Madhu S. and Yang, Eun Sung and Zhang, Baoshan and Zhang, Yi and Asokan, Mangaiarkarasi and Boyington, Jeffrey C. and Bylund, Tatsiana and Darko, Sam and Lees, Christopher R. and Ransier, Amy and Shen, Chen-Hsiang and Wang, Lingshu and Whittle, James R. and Wu, Xueling and Yassine, Hadi M. and Santos, Celia and Matsuoka, Yumiko and Tsybovsky, Yaroslav and Baxa, Ulrich and Mullikin, James C. and Subbarao, Kanta and Douek, Daniel C. and Graham, Barney S. and Koup, Richard A. and Ledgerwood, Julie E. and Roederer, Mario and Shapiro, Lawrence and Kwong, Peter D. and Mascola, John R. and McDermott, Adrian B.},
abstractNote = {},
doi = {10.1016/j.cell.2016.06.043},
journal = {Cell},
number = 3,
volume = 166,
place = {United States},
year = 2016,
month = 7
}
  • Highlights: • Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. • Three human monoclonal antibodies were generated from an H1N1-infected patient. • The antibodies predominantly recognized α-helical stem of viral hemagglutinin (HA). • The antibodies inhibited HA structural activation during the fusion process. • The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize amore » diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short α-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the α-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.« less
  • Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarilymore » targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.« less
  • Research highlights: {yields} The fusion peptide is the only universally conserved epitope in all influenza viral hemagglutinins. {yields} Anti-fusion peptide antibodies are universal antibodies that cross-react with all influenza HA subtypes. {yields} The universal antibodies cross-neutralize different influenza A subtypes. {yields} The universal antibodies inhibit the fusion process between the viruses and the target cells. -- Abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it couldmore » be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.« less