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Proc Natl Acad Sci USA. Broadly neutralizing DNA vaccine with specific mutation alters the antigenicity and sugar-binding activities of influenza hemagglutinin
Broadly neutralizing DNA vaccine with specific mutation alters the antigenicity and sugar-binding activities of influenza hemagglutinin (PNAS, abstract, edited)
[Source: Proc Natl Acad Sci USA, full text: <cite cite="http://www.pnas.org/content/108/9/3510.short?rss=1">Broadly neutralizing DNA vaccine with specific mutation alters the antigenicity and sugar-binding activities of influenza hemagglutinin ? PNAS</cite>. Abstract, edited.]
Broadly neutralizing DNA vaccine with specific mutation alters the antigenicity and sugar-binding activities of influenza hemagglutinin
1. Ming-Wei Chen a,b, 2. Hsin-Yu Liao a,b, 3. Yaoxing Huang c, 4. Jia-Tsrong Jan b, 5. Chih-Cheng Huang d, 6. Chien-Tai Ren b, 7. Chung-Yi Wu b, 8. Ting-Jen Rachel Cheng b, 9. David D. Ho c,1, and 10. Chi-Huey Wong b,1
Author Affiliations
1. a Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan;
2. b Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
3. c Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016; and
4. d Animal Health Research Institute, Council of Agriculture, Tanshui 25158, Taiwan
1. Contributed by Chi-Huey Wong, January 4, 2011 (sent for review December 6, 2010)
* 1 To whom correspondence may be addressed. E-mail: chwong@gate.sinica.edu.tw or dho@adarc.org.
Abstract
The rapid genetic drift of influenza virus hemagglutinin is an obstacle to vaccine efficacy. Previously, we found that the consensus hemagglutinin DNA vaccine (pCHA5) can only elicit moderate neutralization activities toward the H5N1 clade 2.1 and clade 2.3 viruses. Two approaches were thus taken to improve the protection broadness of CHA5. The first one was to include certain surface amino acids that are characteristic of clade 2.3 viruses to improve the protection profiles. When we immunized mice with CHA5 harboring individual mutations, the antibodies elicited by CHA5 containing P157S elicited higher neutralizing activity against the clade 2.3 viruses. Likewise, the viruses pseudotyped with hemagglutinin containing 157S became more susceptible to neutralization. The second approach was to update the consensus sequence with more recent H5N1 strains, generating a second-generation DNA vaccine pCHA5II. We showed that pCHA5II was able to elicit higher cross- neutralization activities against all H5N1 viruses. Comparison of the neutralization profiles of CHA5 and CHA5II, and the animal challenge studies, revealed that CHA5II induced the broadest protection profile. We concluded that CHA5II combined with electroporation delivery is a promising strategy to induce antibodies with broad cross-reactivities against divergent H5N1 influenza viruses.
* serotype * genotype
Footnotes
* Author contributions: D.D.H. and C.-H.W. designed research; M.-W.C., H.-Y.L., J.-T.J., C.-C.H., C.-T.R., and C.-Y.W. performed research; C.-T.R. and C.-Y.W. contributed new reagents/analytic tools; M.-W.C., H.-Y.L., Y.H., T.-J.R.C., D.D.H., and C.-H.W. analyzed data; and M.-W.C., H.-Y.L., Y.H., T.-J.R.C., D.D.H., and C.-H.W. wrote the paper.
* The authors declare no conflict of interest.
* This article contains supporting information online at https://www.pnas.org/lookup/suppl/do...DCSupplemental.
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[Source: Proc Natl Acad Sci USA, full text: <cite cite="http://www.pnas.org/content/108/9/3510.short?rss=1">Broadly neutralizing DNA vaccine with specific mutation alters the antigenicity and sugar-binding activities of influenza hemagglutinin ? PNAS</cite>. Abstract, edited.]
Broadly neutralizing DNA vaccine with specific mutation alters the antigenicity and sugar-binding activities of influenza hemagglutinin
1. Ming-Wei Chen a,b, 2. Hsin-Yu Liao a,b, 3. Yaoxing Huang c, 4. Jia-Tsrong Jan b, 5. Chih-Cheng Huang d, 6. Chien-Tai Ren b, 7. Chung-Yi Wu b, 8. Ting-Jen Rachel Cheng b, 9. David D. Ho c,1, and 10. Chi-Huey Wong b,1
Author Affiliations
1. a Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan;
2. b Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;
3. c Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016; and
4. d Animal Health Research Institute, Council of Agriculture, Tanshui 25158, Taiwan
1. Contributed by Chi-Huey Wong, January 4, 2011 (sent for review December 6, 2010)
* 1 To whom correspondence may be addressed. E-mail: chwong@gate.sinica.edu.tw or dho@adarc.org.
Abstract
The rapid genetic drift of influenza virus hemagglutinin is an obstacle to vaccine efficacy. Previously, we found that the consensus hemagglutinin DNA vaccine (pCHA5) can only elicit moderate neutralization activities toward the H5N1 clade 2.1 and clade 2.3 viruses. Two approaches were thus taken to improve the protection broadness of CHA5. The first one was to include certain surface amino acids that are characteristic of clade 2.3 viruses to improve the protection profiles. When we immunized mice with CHA5 harboring individual mutations, the antibodies elicited by CHA5 containing P157S elicited higher neutralizing activity against the clade 2.3 viruses. Likewise, the viruses pseudotyped with hemagglutinin containing 157S became more susceptible to neutralization. The second approach was to update the consensus sequence with more recent H5N1 strains, generating a second-generation DNA vaccine pCHA5II. We showed that pCHA5II was able to elicit higher cross- neutralization activities against all H5N1 viruses. Comparison of the neutralization profiles of CHA5 and CHA5II, and the animal challenge studies, revealed that CHA5II induced the broadest protection profile. We concluded that CHA5II combined with electroporation delivery is a promising strategy to induce antibodies with broad cross-reactivities against divergent H5N1 influenza viruses.
* serotype * genotype
Footnotes
* Author contributions: D.D.H. and C.-H.W. designed research; M.-W.C., H.-Y.L., J.-T.J., C.-C.H., C.-T.R., and C.-Y.W. performed research; C.-T.R. and C.-Y.W. contributed new reagents/analytic tools; M.-W.C., H.-Y.L., Y.H., T.-J.R.C., D.D.H., and C.-H.W. analyzed data; and M.-W.C., H.-Y.L., Y.H., T.-J.R.C., D.D.H., and C.-H.W. wrote the paper.
* The authors declare no conflict of interest.
* This article contains supporting information online at https://www.pnas.org/lookup/suppl/do...DCSupplemental.
-
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