Vaccine co-display of CSP and Pfs230 on liposomes targeting two Plasmodium falciparum differentiation stages
© 2022. The Author(s)..
A vaccine targeting multiple stages of the Plasmodium falciparum parasite life cycle is desirable. The sporozoite surface Circumsporozoite Protein (CSP) is the target of leading anti-infective P. falciparum pre-erythrocytic vaccines. Pfs230, a sexual-stage P. falciparum surface protein, is currently in trials as the basis for a transmission-blocking vaccine, which inhibits parasite development in the mosquito vector. Here, recombinant full-length CSP and a Pfs230 fragment (Pfs230D1+) are co-displayed on immunogenic liposomes to induce immunity against both infection and transmission. Liposomes contain cobalt-porphyrin phospholipid (CoPoP), monophosphoryl lipid A and QS-21, and rapidly bind His-tagged CSP and Pfs230D1+ upon admixture to form bivalent particles that maintain reactivity with conformational monoclonal antibodies. Use of multicolor fluorophore-labeled antigens reveals liposome binding upon admixture, stability in serum and enhanced uptake in murine macrophages in vitro. Bivalent liposomes induce humoral and cellular responses against both CSP and Pfs230D1+. Vaccine-induced antibodies reduce parasite numbers in mosquito midguts in a standard membrane feeding assay. Mice immunized with liposome-displayed antigens or that passively receive antibodies from immunized rabbits have reduced parasite liver burden following challenge with transgenic sporozoites expressing P. falciparum CSP.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
|---|---|
| Enthalten in: |
Communications biology - 5(2022), 1 vom: 01. Aug., Seite 773 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Wei-Chiao [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Protozoan |
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| Anmerkungen: |
Date Completed 03.08.2022 Date Revised 23.08.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s42003-022-03688-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM344348555 |
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| 100 | 1 | |a Huang, Wei-Chiao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Vaccine co-display of CSP and Pfs230 on liposomes targeting two Plasmodium falciparum differentiation stages |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 03.08.2022 | ||
| 500 | |a Date Revised 23.08.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a A vaccine targeting multiple stages of the Plasmodium falciparum parasite life cycle is desirable. The sporozoite surface Circumsporozoite Protein (CSP) is the target of leading anti-infective P. falciparum pre-erythrocytic vaccines. Pfs230, a sexual-stage P. falciparum surface protein, is currently in trials as the basis for a transmission-blocking vaccine, which inhibits parasite development in the mosquito vector. Here, recombinant full-length CSP and a Pfs230 fragment (Pfs230D1+) are co-displayed on immunogenic liposomes to induce immunity against both infection and transmission. Liposomes contain cobalt-porphyrin phospholipid (CoPoP), monophosphoryl lipid A and QS-21, and rapidly bind His-tagged CSP and Pfs230D1+ upon admixture to form bivalent particles that maintain reactivity with conformational monoclonal antibodies. Use of multicolor fluorophore-labeled antigens reveals liposome binding upon admixture, stability in serum and enhanced uptake in murine macrophages in vitro. Bivalent liposomes induce humoral and cellular responses against both CSP and Pfs230D1+. Vaccine-induced antibodies reduce parasite numbers in mosquito midguts in a standard membrane feeding assay. Mice immunized with liposome-displayed antigens or that passively receive antibodies from immunized rabbits have reduced parasite liver burden following challenge with transgenic sporozoites expressing P. falciparum CSP | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Intramural | |
| 650 | 7 | |a Antibodies, Protozoan |2 NLM | |
| 650 | 7 | |a Antigens |2 NLM | |
| 650 | 7 | |a Liposomes |2 NLM | |
| 650 | 7 | |a Malaria Vaccines |2 NLM | |
| 650 | 7 | |a Protozoan Proteins |2 NLM | |
| 700 | 1 | |a Mabrouk, Moustafa T |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Luwen |e verfasserin |4 aut | |
| 700 | 1 | |a Baba, Minami |e verfasserin |4 aut | |
| 700 | 1 | |a Tachibana, Mayumi |e verfasserin |4 aut | |
| 700 | 1 | |a Torii, Motomi |e verfasserin |4 aut | |
| 700 | 1 | |a Takashima, Eizo |e verfasserin |4 aut | |
| 700 | 1 | |a Locke, Emily |e verfasserin |4 aut | |
| 700 | 1 | |a Plieskatt, Jordan |e verfasserin |4 aut | |
| 700 | 1 | |a King, C Richter |e verfasserin |4 aut | |
| 700 | 1 | |a Coelho, Camila H |e verfasserin |4 aut | |
| 700 | 1 | |a Duffy, Patrick E |e verfasserin |4 aut | |
| 700 | 1 | |a Long, Carole |e verfasserin |4 aut | |
| 700 | 1 | |a Tsuboi, Takafumi |e verfasserin |4 aut | |
| 700 | 1 | |a Miura, Kazutoyo |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yimin |e verfasserin |4 aut | |
| 700 | 1 | |a Ishino, Tomoko |e verfasserin |4 aut | |
| 700 | 1 | |a Lovell, Jonathan F |e verfasserin |4 aut | |
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