Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved..
Malaria transmission-blocking vaccines (TBVs) aim to elicit human antibodies that inhibit sporogonic development of Plasmodium falciparum in mosquitoes, thereby preventing onward transmission. Pfs48/45 is a leading clinical TBV candidate antigen and is recognized by the most potent transmission-blocking monoclonal antibody (mAb) yet described; still, clinical development of Pfs48/45 antigens has been hindered, largely by its poor biochemical characteristics. Here, we used structure-based computational approaches to design Pfs48/45 antigens stabilized in the conformation recognized by the most potently inhibitory mAb, achieving >25°C higher thermostability compared with the wild-type protein. Antibodies elicited in mice immunized with these engineered antigens displayed on liposome-based or protein nanoparticle-based vaccine platforms exhibited 1-2 orders of magnitude superior transmission-reducing activity, compared with immunogens bearing the wild-type antigen, driven by improved antibody quality. Our data provide the founding principles for using molecular stabilization solely from antibody structure-function information to drive improved immune responses against a parasitic vaccine target.
| Errataetall: |
CommentIn: Immunity. 2022 Sep 13;55(9):1588-1590. - PMID 36103857 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:55 |
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| Enthalten in: |
Immunity - 55(2022), 9 vom: 13. Sept., Seite 1680-1692.e8 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
McLeod, Brandon [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.09.2022 Date Revised 14.02.2024 published: Print-Electronic CommentIn: Immunity. 2022 Sep 13;55(9):1588-1590. - PMID 36103857 Citation Status MEDLINE |
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| doi: |
10.1016/j.immuni.2022.07.015 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Vaccination with a structure-based stabilized version of malarial antigen Pfs48/45 elicits ultra-potent transmission-blocking antibody responses |
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| 500 | |a CommentIn: Immunity. 2022 Sep 13;55(9):1588-1590. - PMID 36103857 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Malaria transmission-blocking vaccines (TBVs) aim to elicit human antibodies that inhibit sporogonic development of Plasmodium falciparum in mosquitoes, thereby preventing onward transmission. Pfs48/45 is a leading clinical TBV candidate antigen and is recognized by the most potent transmission-blocking monoclonal antibody (mAb) yet described; still, clinical development of Pfs48/45 antigens has been hindered, largely by its poor biochemical characteristics. Here, we used structure-based computational approaches to design Pfs48/45 antigens stabilized in the conformation recognized by the most potently inhibitory mAb, achieving >25°C higher thermostability compared with the wild-type protein. Antibodies elicited in mice immunized with these engineered antigens displayed on liposome-based or protein nanoparticle-based vaccine platforms exhibited 1-2 orders of magnitude superior transmission-reducing activity, compared with immunogens bearing the wild-type antigen, driven by improved antibody quality. Our data provide the founding principles for using molecular stabilization solely from antibody structure-function information to drive improved immune responses against a parasitic vaccine target | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 4 | |a malaria | |
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| 700 | 1 | |a Miura, Kazutoyo |e verfasserin |4 aut | |
| 700 | 1 | |a Ravichandran, Rashmi |e verfasserin |4 aut | |
| 700 | 1 | |a Kephart, Sally |e verfasserin |4 aut | |
| 700 | 1 | |a Hailemariam, Sophia |e verfasserin |4 aut | |
| 700 | 1 | |a Pham, Thao P |e verfasserin |4 aut | |
| 700 | 1 | |a Semesi, Anthony |e verfasserin |4 aut | |
| 700 | 1 | |a Kucharska, Iga |e verfasserin |4 aut | |
| 700 | 1 | |a Kundu, Prasun |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Wei-Chiao |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Max |e verfasserin |4 aut | |
| 700 | 1 | |a Blackstone, Alyssa |e verfasserin |4 aut | |
| 700 | 1 | |a Pettie, Deleah |e verfasserin |4 aut | |
| 700 | 1 | |a Murphy, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Kraft, John C |e verfasserin |4 aut | |
| 700 | 1 | |a Leaf, Elizabeth M |e verfasserin |4 aut | |
| 700 | 1 | |a Jiao, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a van de Vegte-Bolmer, Marga |e verfasserin |4 aut | |
| 700 | 1 | |a van Gemert, Geert-Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Ramjith, Jordache |e verfasserin |4 aut | |
| 700 | 1 | |a King, C Richter |e verfasserin |4 aut | |
| 700 | 1 | |a MacGill, Randall S |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yimin |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Kelly K |e verfasserin |4 aut | |
| 700 | 1 | |a Jore, Matthijs M |e verfasserin |4 aut | |
| 700 | 1 | |a King, Neil P |e verfasserin |4 aut | |
| 700 | 1 | |a Lovell, Jonathan F |e verfasserin |4 aut | |
| 700 | 1 | |a Julien, Jean-Philippe |e verfasserin |4 aut | |
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