Giuseppe
Emeritus
[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]
Vaccination of monoglycosylated hemagglutinin induces cross-strain protection against influenza virus infections
Juine-Ruey Chen<SUP>a</SUP>,<SUP>1</SUP>, Yueh-Hsiang Yu<SUP>a</SUP>,<SUP>1</SUP>, Yung-Chieh Tseng<SUP>a</SUP>,<SUP>b</SUP>,<SUP>1</SUP>, Wan-Ling Chiang<SUP>a</SUP>, Ming-Feng Chiang<SUP>a</SUP>, Yi-An Ko<SUP>a</SUP>,<SUP>c</SUP>, Yi-Kai Chiu<SUP>a</SUP>,<SUP>c</SUP>, Hsiu-Hua Ma<SUP>a</SUP>, Chung-Yi Wu<SUP>a</SUP>, Jia-Tsrong Jan<SUP>a</SUP>, Kuo-I Lin<SUP>a</SUP>,<SUP>2</SUP>, Che Ma<SUP>a</SUP>,<SUP>2</SUP>, and Chi-Huey Wong<SUP>a</SUP>,<SUP>2</SUP>
<SUP></SUP>
Author Affiliations: <SUP>a</SUP>Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; <SUP>b</SUP>Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; and <SUP>c</SUP>Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan
Contributed by Chi-Huey Wong, December 24, 2013 (sent for review October 14, 2013)
Significance
Influenza epidemics continue to be a threat to public health, and the recent human cases of avian viruses of H5N1, H7N9, and H6N1 in Asia raise the possibility of a new disastrous influenza pandemic. Although an effective universal vaccine that can protect from influenza viruses from different subtypes or even both type A and B is still far from reality, our unique findings, showing that monosaccharide glycosylated HA vaccine induces broader protection against different strains, may lead to a better influenza vaccine design that does not require frequent updates and annual immunizations. This strategy may also map out a new direction for development of universal flu vaccines and be applied to vaccine design for other human viruses.
Abstract
The 2009 H1N1 pandemic and recent human cases of H5N1, H7N9, and H6N1 in Asia highlight the need for a universal influenza vaccine that can provide cross-strain or even cross-subtype protection. Here, we show that recombinant monoglycosylated hemagglutinin (HA<SUB>mg</SUB>) with an intact protein structure from either seasonal or pandemic H1N1 can be used as a vaccine for cross-strain protection against various H1N1 viruses in circulation from 1933 to 2009 in mice and ferrets. In the HA<SUB>mg</SUB> vaccine, highly conserved sequences that were originally covered by glycans in the fully glycosylated HA (HA<SUB>fg</SUB>) are exposed and thus, are better engulfed by dendritic cells (DCs), stimulated better DC maturation, and induced more CD8+ memory T cells and IgG-secreting plasma cells. Single B-cell RT-PCR followed by sequence analysis revealed that the HA<SUB>mg</SUB> vaccine activated more diverse B-cell repertoires than the HA<SUB>fg</SUB> vaccine and produced antibodies with cross-strain binding ability. In summary, the HA<SUB>mg</SUB> vaccine elicits cross-strain immune responses that may mitigate the current need for yearly reformulation of strain-specific inactivated vaccines. This strategy may also map a new direction for universal vaccine design.
glycoprotein engineering - broadly neutralizing antibody
Footnotes
<SUP>1</SUP>J.-R.C., Y.-H.Y., and Y.-C.T. contributed equally to this work.
<SUP>2</SUP>To whom correspondence may be addressed. E-mail: kuoilin@gate.sinica.edu.tw, cma@gate.sinica.edu.tw, or chwong@gate.sinica.edu.tw.
Author contributions: K.-I.L., C.M., and C.-H.W. designed research; J.-R.C., Y.-H.Y., Y.-C.T., W.-L.C., M.-F.C., Y.-A.K., Y.-K.C., H.-H.M., C.-Y.W., and J.-T.J. performed research; J.-R.C., Y.-H.Y., Y.-C.T., W.-L.C., M.-F.C., Y.-A.K., Y.-K.C., H.-H.M., C.-Y.W., J.-T.J., K.-I.L., and C.M. analyzed data; and J.-R.C., Y.-H.Y., Y.-C.T., K.-I.L., C.M., and C.-H.W. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1323954111/-/DCSupplemental.
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Vaccination of monoglycosylated hemagglutinin induces cross-strain protection against influenza virus infections
Juine-Ruey Chen<SUP>a</SUP>,<SUP>1</SUP>, Yueh-Hsiang Yu<SUP>a</SUP>,<SUP>1</SUP>, Yung-Chieh Tseng<SUP>a</SUP>,<SUP>b</SUP>,<SUP>1</SUP>, Wan-Ling Chiang<SUP>a</SUP>, Ming-Feng Chiang<SUP>a</SUP>, Yi-An Ko<SUP>a</SUP>,<SUP>c</SUP>, Yi-Kai Chiu<SUP>a</SUP>,<SUP>c</SUP>, Hsiu-Hua Ma<SUP>a</SUP>, Chung-Yi Wu<SUP>a</SUP>, Jia-Tsrong Jan<SUP>a</SUP>, Kuo-I Lin<SUP>a</SUP>,<SUP>2</SUP>, Che Ma<SUP>a</SUP>,<SUP>2</SUP>, and Chi-Huey Wong<SUP>a</SUP>,<SUP>2</SUP>
<SUP></SUP>
Author Affiliations: <SUP>a</SUP>Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; <SUP>b</SUP>Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; and <SUP>c</SUP>Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan
Contributed by Chi-Huey Wong, December 24, 2013 (sent for review October 14, 2013)
Significance
Influenza epidemics continue to be a threat to public health, and the recent human cases of avian viruses of H5N1, H7N9, and H6N1 in Asia raise the possibility of a new disastrous influenza pandemic. Although an effective universal vaccine that can protect from influenza viruses from different subtypes or even both type A and B is still far from reality, our unique findings, showing that monosaccharide glycosylated HA vaccine induces broader protection against different strains, may lead to a better influenza vaccine design that does not require frequent updates and annual immunizations. This strategy may also map out a new direction for development of universal flu vaccines and be applied to vaccine design for other human viruses.
Abstract
The 2009 H1N1 pandemic and recent human cases of H5N1, H7N9, and H6N1 in Asia highlight the need for a universal influenza vaccine that can provide cross-strain or even cross-subtype protection. Here, we show that recombinant monoglycosylated hemagglutinin (HA<SUB>mg</SUB>) with an intact protein structure from either seasonal or pandemic H1N1 can be used as a vaccine for cross-strain protection against various H1N1 viruses in circulation from 1933 to 2009 in mice and ferrets. In the HA<SUB>mg</SUB> vaccine, highly conserved sequences that were originally covered by glycans in the fully glycosylated HA (HA<SUB>fg</SUB>) are exposed and thus, are better engulfed by dendritic cells (DCs), stimulated better DC maturation, and induced more CD8+ memory T cells and IgG-secreting plasma cells. Single B-cell RT-PCR followed by sequence analysis revealed that the HA<SUB>mg</SUB> vaccine activated more diverse B-cell repertoires than the HA<SUB>fg</SUB> vaccine and produced antibodies with cross-strain binding ability. In summary, the HA<SUB>mg</SUB> vaccine elicits cross-strain immune responses that may mitigate the current need for yearly reformulation of strain-specific inactivated vaccines. This strategy may also map a new direction for universal vaccine design.
glycoprotein engineering - broadly neutralizing antibody
Footnotes
<SUP>1</SUP>J.-R.C., Y.-H.Y., and Y.-C.T. contributed equally to this work.
<SUP>2</SUP>To whom correspondence may be addressed. E-mail: kuoilin@gate.sinica.edu.tw, cma@gate.sinica.edu.tw, or chwong@gate.sinica.edu.tw.
Author contributions: K.-I.L., C.M., and C.-H.W. designed research; J.-R.C., Y.-H.Y., Y.-C.T., W.-L.C., M.-F.C., Y.-A.K., Y.-K.C., H.-H.M., C.-Y.W., and J.-T.J. performed research; J.-R.C., Y.-H.Y., Y.-C.T., W.-L.C., M.-F.C., Y.-A.K., Y.-K.C., H.-H.M., C.-Y.W., J.-T.J., K.-I.L., and C.M. analyzed data; and J.-R.C., Y.-H.Y., Y.-C.T., K.-I.L., C.M., and C.-H.W. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1323954111/-/DCSupplemental.
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