Magnitude and durability of ProC6C-AlOH/Matrix-Mtm vaccine-induced malaria transmission-blocking antibodies in Burkinabe adults from a Phase 1 randomized trial
ProC6C is a multi-stage malaria vaccine designed to disrupt parasite transmission and prevent infection by incorporating three parasite proteins (Pfs230-Pro, Pfs48/45-6C, and CSP) in a single vaccine antigen. The Phase 1 clinical trial (PACTR202201848463189) conducted in Burkina Faso, showed ProC6C-...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
|
| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21645515.2025.2488075 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849763488018202624 |
|---|---|
| author | Mohammad Naghizadeh Kazutoyo Miura Ebenezer Addo Ofori Carole Long Issaka Sagara Alfred B. Tiono Jordan Plieskatt Michael Theisen |
| author_facet | Mohammad Naghizadeh Kazutoyo Miura Ebenezer Addo Ofori Carole Long Issaka Sagara Alfred B. Tiono Jordan Plieskatt Michael Theisen |
| author_sort | Mohammad Naghizadeh |
| collection | DOAJ |
| description | ProC6C is a multi-stage malaria vaccine designed to disrupt parasite transmission and prevent infection by incorporating three parasite proteins (Pfs230-Pro, Pfs48/45-6C, and CSP) in a single vaccine antigen. The Phase 1 clinical trial (PACTR202201848463189) conducted in Burkina Faso, showed ProC6C-AlOH/Matrix-M was safe, well tolerated, immunogenic and generated a functional antibody response to all three constituent antigens at the primary output (D70). As magnitude and durability are central to an efficacious malaria vaccine, analysis was expanded past the initial endpoint, to determine transmission-blocking antibodies (anti-Pfs230 and anti-Pfs48/45-6C) present through D180. Analysis of transmission-reducing activity (TRA) showed 7/20 samples remained biologically active at D180. To identify immune biomarkers for high levels of TRA, the Pfs48/45-6C IgG concentration (calculated relative to the transmission-blocking mAb TB31F) was compared among TRA positive and negative individuals. The magnitude of anti-Pfs48/45-6C IgG had an excellent predictive accuracy (area under the receiver operating curve [ROC AUC] >0.8) with a threshold of 8.7 μg/ml for significant TRA. Additionally, there was significant correlation of TRA and anti-Pfs48/45 epitope I IgG concentration but not significant correlation for anti-Pfs230-Pro IgG, suggesting that vaccine-induced anti-Pfs48/45-6C IgG is the main predictor of TRA. This finding was corroborated by the observation that complement had no effect on TRA in the standard membrane feeding assay (SMFA). Collectively, these efforts confirm the transmission-blocking attributes of ProC6C and suggest that an alternative dosing regimen be evaluated in future clinical trials to improve longevity of functional transmission-reducing antibodies. |
| format | Article |
| id | doaj-art-9cb13a91c573428da28bc23f6b3c31b1 |
| institution | DOAJ |
| issn | 2164-5515 2164-554X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj-art-9cb13a91c573428da28bc23f6b3c31b12025-08-20T03:05:23ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2025-12-0121110.1080/21645515.2025.2488075Magnitude and durability of ProC6C-AlOH/Matrix-Mtm vaccine-induced malaria transmission-blocking antibodies in Burkinabe adults from a Phase 1 randomized trialMohammad Naghizadeh0Kazutoyo Miura1Ebenezer Addo Ofori2Carole Long3Issaka Sagara4Alfred B. Tiono5Jordan Plieskatt6Michael Theisen7Department for Congenital Disorders, Statens Serum Institut (SSI), Copenhagen, DenmarkLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USADepartment for Congenital Disorders, Statens Serum Institut (SSI), Copenhagen, DenmarkLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USAMalaria Research and Training Center, Mali-National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Bamako, MaliGroupe de Recherche Action en Santé (GRAS), Ouagadougou, Burkina FasoDepartment for Congenital Disorders, Statens Serum Institut (SSI), Copenhagen, DenmarkDepartment for Congenital Disorders, Statens Serum Institut (SSI), Copenhagen, DenmarkProC6C is a multi-stage malaria vaccine designed to disrupt parasite transmission and prevent infection by incorporating three parasite proteins (Pfs230-Pro, Pfs48/45-6C, and CSP) in a single vaccine antigen. The Phase 1 clinical trial (PACTR202201848463189) conducted in Burkina Faso, showed ProC6C-AlOH/Matrix-M was safe, well tolerated, immunogenic and generated a functional antibody response to all three constituent antigens at the primary output (D70). As magnitude and durability are central to an efficacious malaria vaccine, analysis was expanded past the initial endpoint, to determine transmission-blocking antibodies (anti-Pfs230 and anti-Pfs48/45-6C) present through D180. Analysis of transmission-reducing activity (TRA) showed 7/20 samples remained biologically active at D180. To identify immune biomarkers for high levels of TRA, the Pfs48/45-6C IgG concentration (calculated relative to the transmission-blocking mAb TB31F) was compared among TRA positive and negative individuals. The magnitude of anti-Pfs48/45-6C IgG had an excellent predictive accuracy (area under the receiver operating curve [ROC AUC] >0.8) with a threshold of 8.7 μg/ml for significant TRA. Additionally, there was significant correlation of TRA and anti-Pfs48/45 epitope I IgG concentration but not significant correlation for anti-Pfs230-Pro IgG, suggesting that vaccine-induced anti-Pfs48/45-6C IgG is the main predictor of TRA. This finding was corroborated by the observation that complement had no effect on TRA in the standard membrane feeding assay (SMFA). Collectively, these efforts confirm the transmission-blocking attributes of ProC6C and suggest that an alternative dosing regimen be evaluated in future clinical trials to improve longevity of functional transmission-reducing antibodies.https://www.tandfonline.com/doi/10.1080/21645515.2025.2488075Malariavaccineantibodiesdurabilityclinical trialMatrix-M |
| spellingShingle | Mohammad Naghizadeh Kazutoyo Miura Ebenezer Addo Ofori Carole Long Issaka Sagara Alfred B. Tiono Jordan Plieskatt Michael Theisen Magnitude and durability of ProC6C-AlOH/Matrix-Mtm vaccine-induced malaria transmission-blocking antibodies in Burkinabe adults from a Phase 1 randomized trial Human Vaccines & Immunotherapeutics Malaria vaccine antibodies durability clinical trial Matrix-M |
| title | Magnitude and durability of ProC6C-AlOH/Matrix-Mtm vaccine-induced malaria transmission-blocking antibodies in Burkinabe adults from a Phase 1 randomized trial |
| title_full | Magnitude and durability of ProC6C-AlOH/Matrix-Mtm vaccine-induced malaria transmission-blocking antibodies in Burkinabe adults from a Phase 1 randomized trial |
| title_fullStr | Magnitude and durability of ProC6C-AlOH/Matrix-Mtm vaccine-induced malaria transmission-blocking antibodies in Burkinabe adults from a Phase 1 randomized trial |
| title_full_unstemmed | Magnitude and durability of ProC6C-AlOH/Matrix-Mtm vaccine-induced malaria transmission-blocking antibodies in Burkinabe adults from a Phase 1 randomized trial |
| title_short | Magnitude and durability of ProC6C-AlOH/Matrix-Mtm vaccine-induced malaria transmission-blocking antibodies in Burkinabe adults from a Phase 1 randomized trial |
| title_sort | magnitude and durability of proc6c aloh matrix mtm vaccine induced malaria transmission blocking antibodies in burkinabe adults from a phase 1 randomized trial |
| topic | Malaria vaccine antibodies durability clinical trial Matrix-M |
| url | https://www.tandfonline.com/doi/10.1080/21645515.2025.2488075 |
| work_keys_str_mv | AT mohammadnaghizadeh magnitudeanddurabilityofproc6calohmatrixmtmvaccineinducedmalariatransmissionblockingantibodiesinburkinabeadultsfromaphase1randomizedtrial AT kazutoyomiura magnitudeanddurabilityofproc6calohmatrixmtmvaccineinducedmalariatransmissionblockingantibodiesinburkinabeadultsfromaphase1randomizedtrial AT ebenezeraddoofori magnitudeanddurabilityofproc6calohmatrixmtmvaccineinducedmalariatransmissionblockingantibodiesinburkinabeadultsfromaphase1randomizedtrial AT carolelong magnitudeanddurabilityofproc6calohmatrixmtmvaccineinducedmalariatransmissionblockingantibodiesinburkinabeadultsfromaphase1randomizedtrial AT issakasagara magnitudeanddurabilityofproc6calohmatrixmtmvaccineinducedmalariatransmissionblockingantibodiesinburkinabeadultsfromaphase1randomizedtrial AT alfredbtiono magnitudeanddurabilityofproc6calohmatrixmtmvaccineinducedmalariatransmissionblockingantibodiesinburkinabeadultsfromaphase1randomizedtrial AT jordanplieskatt magnitudeanddurabilityofproc6calohmatrixmtmvaccineinducedmalariatransmissionblockingantibodiesinburkinabeadultsfromaphase1randomizedtrial AT michaeltheisen magnitudeanddurabilityofproc6calohmatrixmtmvaccineinducedmalariatransmissionblockingantibodiesinburkinabeadultsfromaphase1randomizedtrial |