Cholesterol as an inbuilt immunoadjuvant for a lipopeptide vaccine against group A Streptococcus infection
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
Peptide-based vaccines can trigger highly specific immune responses, although peptides alone are usually unable to confer strong humoral or cellular immunity. Consequently, peptide antigens are administered with immunostimulatory adjuvants, but only a few are safe and effective for human use. To overcome this obstacle, herein a peptide antigen was lipidated to effectively anchor it to liposomes and emulsion. A peptide antigen B cell epitope from Group A Streptococcus M protein was conjugated to a universal T helper epitope, the pan DR-biding epitope (PADRE), alongside a lipidic moiety cholesterol. Compared to a free peptide antigen, the lipidated version (LP1) adopted a helical conformation and self-assembled into small nanoparticles. Surprisingly, LP1 alone induced the same or higher antibody titers than liposomes or emulsion-based formulations. In addition, antibodies produced by mice immunized with LP1 were more opsonic than those induced by administering the antigen with incomplete Freund's adjuvant. No side effects were observed in the immunized mice and no excessive inflammatory immune responses were detected. Overall, this study demonstrated how simple conjugation of cholesterol to a peptide antigen can produce a safe and efficacious vaccine against Group A Streptococcus - the leading cause of superficial infections and the bacteria responsible for deadly post-infection autoimmune disorders.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:663 |
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| Enthalten in: |
Journal of colloid and interface science - 663(2024) vom: 30. März, Seite 43-52 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Alharbi, Nedaa [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.03.2024 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jcis.2024.02.134 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Cholesterol as an inbuilt immunoadjuvant for a lipopeptide vaccine against group A Streptococcus infection |
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| 520 | |a Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Peptide-based vaccines can trigger highly specific immune responses, although peptides alone are usually unable to confer strong humoral or cellular immunity. Consequently, peptide antigens are administered with immunostimulatory adjuvants, but only a few are safe and effective for human use. To overcome this obstacle, herein a peptide antigen was lipidated to effectively anchor it to liposomes and emulsion. A peptide antigen B cell epitope from Group A Streptococcus M protein was conjugated to a universal T helper epitope, the pan DR-biding epitope (PADRE), alongside a lipidic moiety cholesterol. Compared to a free peptide antigen, the lipidated version (LP1) adopted a helical conformation and self-assembled into small nanoparticles. Surprisingly, LP1 alone induced the same or higher antibody titers than liposomes or emulsion-based formulations. In addition, antibodies produced by mice immunized with LP1 were more opsonic than those induced by administering the antigen with incomplete Freund's adjuvant. No side effects were observed in the immunized mice and no excessive inflammatory immune responses were detected. Overall, this study demonstrated how simple conjugation of cholesterol to a peptide antigen can produce a safe and efficacious vaccine against Group A Streptococcus - the leading cause of superficial infections and the bacteria responsible for deadly post-infection autoimmune disorders | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Adjuvant | |
| 650 | 4 | |a Cholesterol | |
| 650 | 4 | |a Group A Streptococcus | |
| 650 | 4 | |a Immunization | |
| 650 | 4 | |a Lipopeptide | |
| 650 | 4 | |a Liposomes or emulsion-based formulations | |
| 650 | 4 | |a Nanoparticles | |
| 650 | 4 | |a Opsonization | |
| 650 | 4 | |a Peptide-based vaccine | |
| 650 | 4 | |a Proinflamatory cytokines | |
| 650 | 7 | |a Adjuvants, Immunologic |2 NLM | |
| 650 | 7 | |a Lipopeptides |2 NLM | |
| 650 | 7 | |a Liposomes |2 NLM | |
| 650 | 7 | |a Emulsions |2 NLM | |
| 650 | 7 | |a Vaccines |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 700 | 1 | |a Shalash, Ahmed O |e verfasserin |4 aut | |
| 700 | 1 | |a Koirala, Prashamsa |e verfasserin |4 aut | |
| 700 | 1 | |a Boer, Jennifer C |e verfasserin |4 aut | |
| 700 | 1 | |a Hussein, Waleed M |e verfasserin |4 aut | |
| 700 | 1 | |a Khalil, Zeinab G |e verfasserin |4 aut | |
| 700 | 1 | |a Capon, Robert J |e verfasserin |4 aut | |
| 700 | 1 | |a Plebanski, Magdalena |e verfasserin |4 aut | |
| 700 | 1 | |a Toth, Istvan |e verfasserin |4 aut | |
| 700 | 1 | |a Skwarczynski, Mariusz |e verfasserin |4 aut | |
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