HIV-1 vaccine design through minimizing envelope metastability

Publication Date:
2018-11-22
Publisher:
American Association for the Advancement of Science (AAAS)
Electronic ISSN:
2375-2548
Topics:
Natural Sciences in General
Published by:
http://www.aaas.org/
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autor He, L., Kumar, S., Allen, J. D., Huang, D., Lin, X., Mann, C. J., Saye-Francisco, K. L., Copps, J., Sarkar, A., Blizard, G. S., Ozorowski, G., Sok, D., Crispin, M., Ward, A. B., Nemazee, D., Burton, D. R., Wilson, I. A., Zhu, J.
beschreibung Overcoming envelope metastability is crucial to trimer-based HIV-1 vaccine design. Here, we present a coherent vaccine strategy by minimizing metastability. For 10 strains across five clades, we demonstrate that the gp41 ectodomain (gp41 ECTO ) is the main source of envelope metastability by replacing wild-type gp41 ECTO with BG505 gp41 ECTO of the uncleaved prefusion-optimized (UFO) design. These gp41 ECTO -swapped trimers can be produced in CHO cells with high yield and high purity. The crystal structure of a gp41 ECTO -swapped trimer elucidates how a neutralization-resistant tier 3 virus evades antibody recognition of the V2 apex. UFO trimers of transmitted/founder viruses and UFO trimers containing a consensus-based ancestral gp41 ECTO suggest an evolutionary root of metastability. The gp41 ECTO -stabilized trimers can be readily displayed on 24- and 60-meric nanoparticles, with incorporation of additional T cell help illustrated for a hyperstable 60-mer, I3-01. In mice and rabbits, these gp140 nanoparticles induced tier 2 neutralizing antibody responses more effectively than soluble trimers.
citation_standardnr 6359995
datenlieferant ipn_articles
feed_id 228416
feed_publisher American Association for the Advancement of Science (AAAS)
feed_publisher_url http://www.aaas.org/
insertion_date 2018-11-22
journaleissn 2375-2548
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Association for the Advancement of Science (AAAS)
quelle Science Advances
relation http://advances.sciencemag.org/cgi/content/short/4/11/eaau6769?rss=1
search_space articles
shingle_author_1 He, L., Kumar, S., Allen, J. D., Huang, D., Lin, X., Mann, C. J., Saye-Francisco, K. L., Copps, J., Sarkar, A., Blizard, G. S., Ozorowski, G., Sok, D., Crispin, M., Ward, A. B., Nemazee, D., Burton, D. R., Wilson, I. A., Zhu, J.
shingle_author_2 He, L., Kumar, S., Allen, J. D., Huang, D., Lin, X., Mann, C. J., Saye-Francisco, K. L., Copps, J., Sarkar, A., Blizard, G. S., Ozorowski, G., Sok, D., Crispin, M., Ward, A. B., Nemazee, D., Burton, D. R., Wilson, I. A., Zhu, J.
shingle_author_3 He, L., Kumar, S., Allen, J. D., Huang, D., Lin, X., Mann, C. J., Saye-Francisco, K. L., Copps, J., Sarkar, A., Blizard, G. S., Ozorowski, G., Sok, D., Crispin, M., Ward, A. B., Nemazee, D., Burton, D. R., Wilson, I. A., Zhu, J.
shingle_author_4 He, L., Kumar, S., Allen, J. D., Huang, D., Lin, X., Mann, C. J., Saye-Francisco, K. L., Copps, J., Sarkar, A., Blizard, G. S., Ozorowski, G., Sok, D., Crispin, M., Ward, A. B., Nemazee, D., Burton, D. R., Wilson, I. A., Zhu, J.
shingle_catch_all_1 HIV-1 vaccine design through minimizing envelope metastability
Overcoming envelope metastability is crucial to trimer-based HIV-1 vaccine design. Here, we present a coherent vaccine strategy by minimizing metastability. For 10 strains across five clades, we demonstrate that the gp41 ectodomain (gp41 ECTO ) is the main source of envelope metastability by replacing wild-type gp41 ECTO with BG505 gp41 ECTO of the uncleaved prefusion-optimized (UFO) design. These gp41 ECTO -swapped trimers can be produced in CHO cells with high yield and high purity. The crystal structure of a gp41 ECTO -swapped trimer elucidates how a neutralization-resistant tier 3 virus evades antibody recognition of the V2 apex. UFO trimers of transmitted/founder viruses and UFO trimers containing a consensus-based ancestral gp41 ECTO suggest an evolutionary root of metastability. The gp41 ECTO -stabilized trimers can be readily displayed on 24- and 60-meric nanoparticles, with incorporation of additional T cell help illustrated for a hyperstable 60-mer, I3-01. In mice and rabbits, these gp140 nanoparticles induced tier 2 neutralizing antibody responses more effectively than soluble trimers.
He, L., Kumar, S., Allen, J. D., Huang, D., Lin, X., Mann, C. J., Saye-Francisco, K. L., Copps, J., Sarkar, A., Blizard, G. S., Ozorowski, G., Sok, D., Crispin, M., Ward, A. B., Nemazee, D., Burton, D. R., Wilson, I. A., Zhu, J.
American Association for the Advancement of Science (AAAS)
2375-2548
23752548
shingle_catch_all_2 HIV-1 vaccine design through minimizing envelope metastability
Overcoming envelope metastability is crucial to trimer-based HIV-1 vaccine design. Here, we present a coherent vaccine strategy by minimizing metastability. For 10 strains across five clades, we demonstrate that the gp41 ectodomain (gp41 ECTO ) is the main source of envelope metastability by replacing wild-type gp41 ECTO with BG505 gp41 ECTO of the uncleaved prefusion-optimized (UFO) design. These gp41 ECTO -swapped trimers can be produced in CHO cells with high yield and high purity. The crystal structure of a gp41 ECTO -swapped trimer elucidates how a neutralization-resistant tier 3 virus evades antibody recognition of the V2 apex. UFO trimers of transmitted/founder viruses and UFO trimers containing a consensus-based ancestral gp41 ECTO suggest an evolutionary root of metastability. The gp41 ECTO -stabilized trimers can be readily displayed on 24- and 60-meric nanoparticles, with incorporation of additional T cell help illustrated for a hyperstable 60-mer, I3-01. In mice and rabbits, these gp140 nanoparticles induced tier 2 neutralizing antibody responses more effectively than soluble trimers.
He, L., Kumar, S., Allen, J. D., Huang, D., Lin, X., Mann, C. J., Saye-Francisco, K. L., Copps, J., Sarkar, A., Blizard, G. S., Ozorowski, G., Sok, D., Crispin, M., Ward, A. B., Nemazee, D., Burton, D. R., Wilson, I. A., Zhu, J.
American Association for the Advancement of Science (AAAS)
2375-2548
23752548
shingle_catch_all_3 HIV-1 vaccine design through minimizing envelope metastability
Overcoming envelope metastability is crucial to trimer-based HIV-1 vaccine design. Here, we present a coherent vaccine strategy by minimizing metastability. For 10 strains across five clades, we demonstrate that the gp41 ectodomain (gp41 ECTO ) is the main source of envelope metastability by replacing wild-type gp41 ECTO with BG505 gp41 ECTO of the uncleaved prefusion-optimized (UFO) design. These gp41 ECTO -swapped trimers can be produced in CHO cells with high yield and high purity. The crystal structure of a gp41 ECTO -swapped trimer elucidates how a neutralization-resistant tier 3 virus evades antibody recognition of the V2 apex. UFO trimers of transmitted/founder viruses and UFO trimers containing a consensus-based ancestral gp41 ECTO suggest an evolutionary root of metastability. The gp41 ECTO -stabilized trimers can be readily displayed on 24- and 60-meric nanoparticles, with incorporation of additional T cell help illustrated for a hyperstable 60-mer, I3-01. In mice and rabbits, these gp140 nanoparticles induced tier 2 neutralizing antibody responses more effectively than soluble trimers.
He, L., Kumar, S., Allen, J. D., Huang, D., Lin, X., Mann, C. J., Saye-Francisco, K. L., Copps, J., Sarkar, A., Blizard, G. S., Ozorowski, G., Sok, D., Crispin, M., Ward, A. B., Nemazee, D., Burton, D. R., Wilson, I. A., Zhu, J.
American Association for the Advancement of Science (AAAS)
2375-2548
23752548
shingle_catch_all_4 HIV-1 vaccine design through minimizing envelope metastability
Overcoming envelope metastability is crucial to trimer-based HIV-1 vaccine design. Here, we present a coherent vaccine strategy by minimizing metastability. For 10 strains across five clades, we demonstrate that the gp41 ectodomain (gp41 ECTO ) is the main source of envelope metastability by replacing wild-type gp41 ECTO with BG505 gp41 ECTO of the uncleaved prefusion-optimized (UFO) design. These gp41 ECTO -swapped trimers can be produced in CHO cells with high yield and high purity. The crystal structure of a gp41 ECTO -swapped trimer elucidates how a neutralization-resistant tier 3 virus evades antibody recognition of the V2 apex. UFO trimers of transmitted/founder viruses and UFO trimers containing a consensus-based ancestral gp41 ECTO suggest an evolutionary root of metastability. The gp41 ECTO -stabilized trimers can be readily displayed on 24- and 60-meric nanoparticles, with incorporation of additional T cell help illustrated for a hyperstable 60-mer, I3-01. In mice and rabbits, these gp140 nanoparticles induced tier 2 neutralizing antibody responses more effectively than soluble trimers.
He, L., Kumar, S., Allen, J. D., Huang, D., Lin, X., Mann, C. J., Saye-Francisco, K. L., Copps, J., Sarkar, A., Blizard, G. S., Ozorowski, G., Sok, D., Crispin, M., Ward, A. B., Nemazee, D., Burton, D. R., Wilson, I. A., Zhu, J.
American Association for the Advancement of Science (AAAS)
2375-2548
23752548
shingle_title_1 HIV-1 vaccine design through minimizing envelope metastability
shingle_title_2 HIV-1 vaccine design through minimizing envelope metastability
shingle_title_3 HIV-1 vaccine design through minimizing envelope metastability
shingle_title_4 HIV-1 vaccine design through minimizing envelope metastability
timestamp 2025-06-30T23:37:27.176Z
titel HIV-1 vaccine design through minimizing envelope metastability
titel_suche HIV-1 vaccine design through minimizing envelope metastability
topic TA-TD
uid ipn_articles_6359995