Impact of a blood-stage vaccine on Plasmodium vivax malaria
Background: There are no licensed vaccines against Plasmodium vivax , the most common cause of malaria outside of Africa.
Methods: We conducted two Phase I/IIa clinical trials to assess the safety, immunogenicity and efficacy of two vaccines targeting region II of P. vivax Duffy-binding protein (PvDBPII). Recombinant viral vaccines (using ChAd63 and MVA vectors) were administered at 0, 2 months or in a delayed dosing regimen (0, 17, 19 months), whilst a protein/adjuvant formulation (PvDBPII/Matrix-M™) was administered monthly (0, 1, 2 months) or in a delayed dosing regimen (0, 1, 14 months). Delayed regimens were due to trial halts during the COVID-19 pandemic. Volunteers underwent heterologous controlled human malaria infection (CHMI) with blood-stage P. vivax parasites at 2-4 weeks following their last vaccination, alongside unvaccinated controls. Efficacy was assessed by comparison of parasite multiplication rate (PMR) in blood post-CHMI, modelled from parasitemia measured by quantitative polymerase-chain-reaction (qPCR).
Results: Thirty-two volunteers were enrolled and vaccinated (n=16 for each vaccine). No safety concerns were identified. PvDBPII/Matrix-M™, given in the delayed dosing regimen, elicited the highest antibody responses and reduced the mean PMR following CHMI by 51% (range 36-66%; n=6) compared to unvaccinated controls (n=13). No other vaccine or regimen impacted parasite growth. In vivo growth inhibition of blood-stage P. vivax correlated with functional antibody readouts of vaccine immunogenicity.
Conclusions: Vaccination of malaria-naïve adults with a delayed booster regimen of PvDBPII/ Matrix-M™ significantly reduces the growth of blood-stage P. vivax . Funded by the European Commission and Wellcome Trust; VAC069, VAC071 and VAC079 ClinicalTrials.gov numbers NCT03797989 , NCT04009096 and NCT04201431.
| Errataetall: |
UpdateIn: Sci Transl Med. 2023 Jul 12;15(704):eadf1782. - PMID 37437014 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2022 |
|---|---|
| Enthalten in: |
medRxiv : the preprint server for health sciences - (2022) vom: 30. Mai |
| Sprache: |
Englisch |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 29.09.2023 published: Electronic ClinicalTrials.gov: NCT04201431, NCT04009096, NCT03797989 UpdateIn: Sci Transl Med. 2023 Jul 12;15(704):eadf1782. - PMID 37437014 Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1101/2022.05.27.22275375 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM341868825 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM341868825 | ||
| 003 | DE-627 | ||
| 005 | 20231226012749.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2022.05.27.22275375 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1139.xml |
| 035 | |a (DE-627)NLM341868825 | ||
| 035 | |a (NLM)35664997 | ||
| 035 | |a (PII)2022.05.27.22275375 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hou, Mimi M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Impact of a blood-stage vaccine on Plasmodium vivax malaria |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 29.09.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04201431, NCT04009096, NCT03797989 | ||
| 500 | |a UpdateIn: Sci Transl Med. 2023 Jul 12;15(704):eadf1782. - PMID 37437014 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Background: There are no licensed vaccines against Plasmodium vivax , the most common cause of malaria outside of Africa | ||
| 520 | |a Methods: We conducted two Phase I/IIa clinical trials to assess the safety, immunogenicity and efficacy of two vaccines targeting region II of P. vivax Duffy-binding protein (PvDBPII). Recombinant viral vaccines (using ChAd63 and MVA vectors) were administered at 0, 2 months or in a delayed dosing regimen (0, 17, 19 months), whilst a protein/adjuvant formulation (PvDBPII/Matrix-M™) was administered monthly (0, 1, 2 months) or in a delayed dosing regimen (0, 1, 14 months). Delayed regimens were due to trial halts during the COVID-19 pandemic. Volunteers underwent heterologous controlled human malaria infection (CHMI) with blood-stage P. vivax parasites at 2-4 weeks following their last vaccination, alongside unvaccinated controls. Efficacy was assessed by comparison of parasite multiplication rate (PMR) in blood post-CHMI, modelled from parasitemia measured by quantitative polymerase-chain-reaction (qPCR) | ||
| 520 | |a Results: Thirty-two volunteers were enrolled and vaccinated (n=16 for each vaccine). No safety concerns were identified. PvDBPII/Matrix-M™, given in the delayed dosing regimen, elicited the highest antibody responses and reduced the mean PMR following CHMI by 51% (range 36-66%; n=6) compared to unvaccinated controls (n=13). No other vaccine or regimen impacted parasite growth. In vivo growth inhibition of blood-stage P. vivax correlated with functional antibody readouts of vaccine immunogenicity | ||
| 520 | |a Conclusions: Vaccination of malaria-naïve adults with a delayed booster regimen of PvDBPII/ Matrix-M™ significantly reduces the growth of blood-stage P. vivax . Funded by the European Commission and Wellcome Trust; VAC069, VAC071 and VAC079 ClinicalTrials.gov numbers NCT03797989 , NCT04009096 and NCT04201431 | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a Barrett, Jordan R |e verfasserin |4 aut | |
| 700 | 1 | |a Themistocleous, Yrene |e verfasserin |4 aut | |
| 700 | 1 | |a Rawlinson, Thomas A |e verfasserin |4 aut | |
| 700 | 1 | |a Diouf, Ababacar |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez, Francisco J |e verfasserin |4 aut | |
| 700 | 1 | |a Nielsen, Carolyn M |e verfasserin |4 aut | |
| 700 | 1 | |a Lias, Amelia M |e verfasserin |4 aut | |
| 700 | 1 | |a King, Lloyd D W |e verfasserin |4 aut | |
| 700 | 1 | |a Edwards, Nick J |e verfasserin |4 aut | |
| 700 | 1 | |a Greenwood, Nicola M |e verfasserin |4 aut | |
| 700 | 1 | |a Kingham, Lucy |e verfasserin |4 aut | |
| 700 | 1 | |a Poulton, Ian D |e verfasserin |4 aut | |
| 700 | 1 | |a Khozoee, Baktash |e verfasserin |4 aut | |
| 700 | 1 | |a Goh, Cyndi |e verfasserin |4 aut | |
| 700 | 1 | |a Mac Lochlainn, Dylan J |e verfasserin |4 aut | |
| 700 | 1 | |a Salkeld, Jo |e verfasserin |4 aut | |
| 700 | 1 | |a Guilotte-Blisnick, Micheline |e verfasserin |4 aut | |
| 700 | 1 | |a Huon, Christèle |e verfasserin |4 aut | |
| 700 | 1 | |a Mohring, Franziska |e verfasserin |4 aut | |
| 700 | 1 | |a Reimer, Jenny M |e verfasserin |4 aut | |
| 700 | 1 | |a Chauhan, Virander S |e verfasserin |4 aut | |
| 700 | 1 | |a Mukherjee, Paushali |e verfasserin |4 aut | |
| 700 | 1 | |a Biswas, Sumi |e verfasserin |4 aut | |
| 700 | 1 | |a Taylor, Iona J |e verfasserin |4 aut | |
| 700 | 1 | |a Lawrie, Alison M |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Jee-Sun |e verfasserin |4 aut | |
| 700 | 1 | |a Nugent, Fay L |e verfasserin |4 aut | |
| 700 | 1 | |a Long, Carole A |e verfasserin |4 aut | |
| 700 | 1 | |a Moon, Robert W |e verfasserin |4 aut | |
| 700 | 1 | |a Miura, Kazutoyo |e verfasserin |4 aut | |
| 700 | 1 | |a Silk, Sarah E |e verfasserin |4 aut | |
| 700 | 1 | |a Chitnis, Chetan E |e verfasserin |4 aut | |
| 700 | 1 | |a Minassian, Angela M |e verfasserin |4 aut | |
| 700 | 1 | |a Draper, Simon J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t medRxiv : the preprint server for health sciences |d 2020 |g (2022) vom: 30. Mai |w (DE-627)NLM310900166 |7 nnns |
| 773 | 1 | 8 | |g year:2022 |g day:30 |g month:05 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2022.05.27.22275375 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2022 |b 30 |c 05 | ||