A HIV-1 Gp41 Peptide-Liposome Vaccine Elicits Neutralizing Epitope-Targeted Antibody Responses in Healthy Individuals
Background: HIV-1 vaccine development is a global health priority. Broadly neutralizing antibodies (bnAbs) which target the HIV-1 gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand bnAb precursors in monkeys.
Methods: The HVTN133 phase 1 clinical trial (NCT03934541) studied the MPER-peptide liposome immunogen in 24 HIV-1 seronegative individuals. Participants were recruited between 15 July 2019 and 18 October 2019 and were randomized in a dose-escalation design to either 500 mcg or 2000 mcg of the MPER-peptide liposome or placebo. Four intramuscular injections were planned at months 0, 2, 6, and 12.
Results: The trial was stopped prematurely due to an anaphylaxis reaction in one participant ultimately attributed to vaccine-associated polyethylene glycol. The immunogen induced robust immune responses, including MPER+ serum and blood CD4+ T-cell responses in 95% and 100% of vaccinees, respectively, and 35% (7/20) of vaccine recipients had blood IgG memory B cells with MPER-bnAb binding phenotype. Affinity purification of plasma MPER+ IgG demonstrated tier 2 HIV-1 neutralizing activity in two of five participants after 3 immunizations.
Conclusions: MPER-peptide liposomes induced gp41 serum neutralizing epitope-targeted antibodies and memory B-cell responses in humans despite the early termination of the study. These results suggest that the MPER region is a promising target for a candidate HIV vaccine.
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E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
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Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
medRxiv : the preprint server for health sciences - (2024) vom: 18. März |
| Sprache: |
Englisch |
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Date Revised 08.04.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2024.03.15.24304305 |
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| PPN (Katalog-ID): |
NLM370523393 |
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| 100 | 1 | |a Erdmann, Nathan B |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A HIV-1 Gp41 Peptide-Liposome Vaccine Elicits Neutralizing Epitope-Targeted Antibody Responses in Healthy Individuals |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 08.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Background: HIV-1 vaccine development is a global health priority. Broadly neutralizing antibodies (bnAbs) which target the HIV-1 gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand bnAb precursors in monkeys | ||
| 520 | |a Methods: The HVTN133 phase 1 clinical trial (NCT03934541) studied the MPER-peptide liposome immunogen in 24 HIV-1 seronegative individuals. Participants were recruited between 15 July 2019 and 18 October 2019 and were randomized in a dose-escalation design to either 500 mcg or 2000 mcg of the MPER-peptide liposome or placebo. Four intramuscular injections were planned at months 0, 2, 6, and 12 | ||
| 520 | |a Results: The trial was stopped prematurely due to an anaphylaxis reaction in one participant ultimately attributed to vaccine-associated polyethylene glycol. The immunogen induced robust immune responses, including MPER+ serum and blood CD4+ T-cell responses in 95% and 100% of vaccinees, respectively, and 35% (7/20) of vaccine recipients had blood IgG memory B cells with MPER-bnAb binding phenotype. Affinity purification of plasma MPER+ IgG demonstrated tier 2 HIV-1 neutralizing activity in two of five participants after 3 immunizations | ||
| 520 | |a Conclusions: MPER-peptide liposomes induced gp41 serum neutralizing epitope-targeted antibodies and memory B-cell responses in humans despite the early termination of the study. These results suggest that the MPER region is a promising target for a candidate HIV vaccine | ||
| 650 | 4 | |a Preprint | |
| 650 | 4 | |a Fusion Proteins | |
| 650 | 4 | |a HIV Vaccine | |
| 650 | 4 | |a Immunogenicity | |
| 650 | 4 | |a Liposome | |
| 700 | 1 | |a Williams, Wilton B |e verfasserin |4 aut | |
| 700 | 1 | |a Walsh, Stephen R |e verfasserin |4 aut | |
| 700 | 1 | |a Grunenberg, Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Edlefsen, Paul T |e verfasserin |4 aut | |
| 700 | 1 | |a Goepfert, Paul A |e verfasserin |4 aut | |
| 700 | 1 | |a Cain, Derek W |e verfasserin |4 aut | |
| 700 | 1 | |a Cohen, Kristen W |e verfasserin |4 aut | |
| 700 | 1 | |a Maenza, Janine |e verfasserin |4 aut | |
| 700 | 1 | |a Mayer, Kenneth H |e verfasserin |4 aut | |
| 700 | 1 | |a Tieu, Hong Van |e verfasserin |4 aut | |
| 700 | 1 | |a Sobieszczyk, Magdalena E |e verfasserin |4 aut | |
| 700 | 1 | |a Swann, Edith |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Huiyin |e verfasserin |4 aut | |
| 700 | 1 | |a De Rosa, Stephen C |e verfasserin |4 aut | |
| 700 | 1 | |a Sagawa, Zachary |e verfasserin |4 aut | |
| 700 | 1 | |a Moody, M Anthony |e verfasserin |4 aut | |
| 700 | 1 | |a Fox, Christopher B |e verfasserin |4 aut | |
| 700 | 1 | |a Ferrari, Guido |e verfasserin |4 aut | |
| 700 | 1 | |a Edwards, R J |e verfasserin |4 aut | |
| 700 | 1 | |a Acharya, Priyamvada |e verfasserin |4 aut | |
| 700 | 1 | |a Alam, S Munir |e verfasserin |4 aut | |
| 700 | 1 | |a Parks, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Barr, Margaret |e verfasserin |4 aut | |
| 700 | 1 | |a Tomaras, Georgia D |e verfasserin |4 aut | |
| 700 | 1 | |a Montefiori, David C |e verfasserin |4 aut | |
| 700 | 1 | |a Gilbert, Peter B |e verfasserin |4 aut | |
| 700 | 1 | |a McElrath, M Juliana |e verfasserin |4 aut | |
| 700 | 1 | |a Corey, Lawrence |e verfasserin |4 aut | |
| 700 | 1 | |a Haynes, Barton F |e verfasserin |4 aut | |
| 700 | 1 | |a Baden, Lindsey R |e verfasserin |4 aut | |
| 700 | 0 | |a NIAID HVTN 133 Study Group |e verfasserin |4 aut | |
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