Periodic Reporting for period 2 - ADVANCE-VAC4PM (Advancing The Clinical Development Of Placental Malaria Vaccines In The Context Of Capacity Building and Use Of Digital Health Technologies)
Periodo di rendicontazione: 2023-12-01 al 2025-05-31
Placental Malaria (PM) represents a major health problem affecting particularly vulnerable demographic groups, pregnant women and their babies in Plasmodium falciparum endemic regions. An effective vaccine would be an attractive tool to control PM, acting early on during pregnancy and complementing other control strategies. The VAR2CSA pregnancy-specific variant of the P. falciparum Erythrocyte Membrane Protein 1 family is the leading target for such a vaccine.
ADVANCE-VAC4PM builds on the success of previous phase Ia/Ib clinical trials assessing two VAR2CSA-derived vaccine candidates, PRIMVAC and PAMVAC, in malaria-naïve and lifelong P. falciparum-exposed non-pregnant women. Both vaccine candidates were safe, well-tolerated and induced good homologous immune responses, demonstrating the feasibility of developing a PM vaccine. Building upon these results, the overall project objective is to advance the development of PM vaccine candidates and broaden the vaccines’ induced immune response by i) using a novel vaccine platform based on capside-Virus-Like Particles (cVLPs) to display PAMVAC and ii) by evaluating if a PRIMVAC/PAMVAC-cVLP co-administration approach increases cross-reactivity and cross-inhibitory antibody titers.
These activities are embedded in capacity building activities e.g. workshops, training of MSc/PhD students, mentorship program for African early career researchers and development of immunology laboratory capacity.
In preparation of future PM vaccine trials, digital tools, the potential cost-effectiveness of a PM vaccine introduction and the feasibility and acceptability of PM vaccines are being evaluated. Awareness on the need for a PM vaccine will be raised in stakeholder engagement activities.
ADVANCE-VAC4PM builds on the success of previous phase Ia/Ib clinical trials assessing two VAR2CSA-derived vaccine candidates, PRIMVAC and PAMVAC, in malaria-naïve and lifelong P. falciparum-exposed non-pregnant women. Both vaccine candidates were safe, well-tolerated and induced good homologous immune responses, demonstrating the feasibility of developing a PM vaccine. Building upon these results, the overall project objective is to advance the development of PM vaccine candidates and broaden the vaccines’ induced immune response by i) using a novel vaccine platform based on capside-Virus-Like Particles (cVLPs) to display PAMVAC and ii) by evaluating if a PRIMVAC/PAMVAC-cVLP co-administration approach increases cross-reactivity and cross-inhibitory antibody titers.
These activities are embedded in capacity building activities e.g. workshops, training of MSc/PhD students, mentorship program for African early career researchers and development of immunology laboratory capacity.
In preparation of future PM vaccine trials, digital tools, the potential cost-effectiveness of a PM vaccine introduction and the feasibility and acceptability of PM vaccines are being evaluated. Awareness on the need for a PM vaccine will be raised in stakeholder engagement activities.
For the conduct of the planned clinical trials, clinical batches of the PRIMVAC and PAMVAC-cVLP vaccine candidates are being manufactured by the selected Contract Manufacturing Organization (CMO) with GMP release expected in Q4 2025. Planning of the phase Ia/Ib clinical trial to be conducted at Radboudumc (The Netherlands) and GRAS (Burkina Faso) is ongoing. A study protocol has been drafted. A VAR2CSA multiplex immunoassay for assessing endpoints in the clinical trials is set up at Radboudumc. Phase 2 study design modelling activities have been initiated.
In the context of the eHealth activities, the mobile application to monitor pregnancy outcomes was selected and adapted for use in this project. The EVAPREAP research study for the creation of electronic pregnancy registers and qualitative evaluation of the selected mobile application has been completed at the four African sites: FORS (Benin), GRAS (Burkina Faso), KHRC (Ghana) and MUST (Malawi) and data analysis is ongoing.
The modelling cost-effectiveness study to evaluate the benefit of introducing a PM vaccine in Malawi has been completed and preliminary results are available. As part of the engagement activities, a workshop on “Strategies for Using Malaria Vaccines to Prevent Malaria in Pregnancy” has been organized to initiate discussions on how to successfully roll-out and implement vaccines targeting malaria in pregnancy, with insights from global health experts and relevant stakeholders.
Finally, human and infrastructure capacity building activities are ongoing and will continue throughout the project to strengthen clinical and immunological capacities at the African sites.
In the context of the eHealth activities, the mobile application to monitor pregnancy outcomes was selected and adapted for use in this project. The EVAPREAP research study for the creation of electronic pregnancy registers and qualitative evaluation of the selected mobile application has been completed at the four African sites: FORS (Benin), GRAS (Burkina Faso), KHRC (Ghana) and MUST (Malawi) and data analysis is ongoing.
The modelling cost-effectiveness study to evaluate the benefit of introducing a PM vaccine in Malawi has been completed and preliminary results are available. As part of the engagement activities, a workshop on “Strategies for Using Malaria Vaccines to Prevent Malaria in Pregnancy” has been organized to initiate discussions on how to successfully roll-out and implement vaccines targeting malaria in pregnancy, with insights from global health experts and relevant stakeholders.
Finally, human and infrastructure capacity building activities are ongoing and will continue throughout the project to strengthen clinical and immunological capacities at the African sites.
The results of the clinical trials planned within the ADVANCE_VAC4PM project will contribute to advancing the development of two promising PM vaccine candidates, preparing for larger and more costly proof-of-concept phase II/III clinical trials.
The further assessment of mobile applications for monitoring pregnancy outcomes and development of pregnancy registers will build the base for future PM vaccine efficacy trials and any other interventions in pregnant women. If acceptability and feasibility can be demonstrated, mobile applications could be further improved and evaluated to promote and improve uptake and continued access to essential maternal and neonatal care services.
The clinical trial results will also be complemented by the evaluation of the economic and socio-cultural factors that can strongly influence the implementation, delivery and sustainability of a PM vaccine intervention. A close dialogue with health care providers and professionals, decision-makers and public health authorities in sub-Saharan Africa is crucial for the uptake of new research results into policy and practice. Community engagement activities across the different African sites will pave the way for smooth implementation of any activities and new interventions. These activities will help to provide a better understanding of PM and the potential impact of a vaccine to prevent PM in sub-Saharan Africa.
The further assessment of mobile applications for monitoring pregnancy outcomes and development of pregnancy registers will build the base for future PM vaccine efficacy trials and any other interventions in pregnant women. If acceptability and feasibility can be demonstrated, mobile applications could be further improved and evaluated to promote and improve uptake and continued access to essential maternal and neonatal care services.
The clinical trial results will also be complemented by the evaluation of the economic and socio-cultural factors that can strongly influence the implementation, delivery and sustainability of a PM vaccine intervention. A close dialogue with health care providers and professionals, decision-makers and public health authorities in sub-Saharan Africa is crucial for the uptake of new research results into policy and practice. Community engagement activities across the different African sites will pave the way for smooth implementation of any activities and new interventions. These activities will help to provide a better understanding of PM and the potential impact of a vaccine to prevent PM in sub-Saharan Africa.