Periodic Reporting for period 1 - ADVANCE-VAC4PM (Advancing The Clinical Development Of Placental Malaria Vaccines In The Context Of Capacity Building and Use Of Digital Health Technologies)
Período documentado: 2022-06-01 hasta 2023-11-30
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 will build on the success of previous studies assessing two VAR2CSA-derived vaccine candidates, PRIMVAC and PAMVAC, in phase Ia/Ib clinical trials 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. However, prior to embarking on costly, large scale phase II clinical trials, it is essential to optimize the cross-reactivity of the vaccines. The overall project objective is to advance the PM vaccine development and to broaden the immune response by i) increasing the vaccine-induced antibody level by using Virus-Like particles (VLP) to display the PM antigens or ii) by evaluating if a co-administration approach using PRIMVAC and PAMVAC-cVLP will increase cross-reactivity and cross-inhibitory antibody titers.
These activities will be embedded in capacity building activities e.g. workshops, training of MSc/PhD students, small competitive research grants to African early career researchers and development of immunology laboratory capacity.
In preparation of future PM vaccine trials, digital tools will be evaluated. Pregnancy registers will be developed and the feasibility and acceptability of using mobile applications for tracking pregnancy outcomes will be assessed. Modelling the cost-effectiveness, feasibility and acceptability of PM vaccines will further strengthen the case. Awareness on the need for a PM vaccine will be raised in stakeholder engagement activities.
ADVANCE-VAC4PM will build on the success of previous studies assessing two VAR2CSA-derived vaccine candidates, PRIMVAC and PAMVAC, in phase Ia/Ib clinical trials 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. However, prior to embarking on costly, large scale phase II clinical trials, it is essential to optimize the cross-reactivity of the vaccines. The overall project objective is to advance the PM vaccine development and to broaden the immune response by i) increasing the vaccine-induced antibody level by using Virus-Like particles (VLP) to display the PM antigens or ii) by evaluating if a co-administration approach using PRIMVAC and PAMVAC-cVLP will increase cross-reactivity and cross-inhibitory antibody titers.
These activities will be embedded in capacity building activities e.g. workshops, training of MSc/PhD students, small competitive research grants to African early career researchers and development of immunology laboratory capacity.
In preparation of future PM vaccine trials, digital tools will be evaluated. Pregnancy registers will be developed and the feasibility and acceptability of using mobile applications for tracking pregnancy outcomes will be assessed. Modelling the cost-effectiveness, feasibility and acceptability of PM vaccines will further strengthen the case. Awareness on the need for a PM vaccine will be raised in stakeholder engagement activities.
For the conduct of the planned clinical trials, GMP batches of the PRIMVAC and PAMVAC-cVLP vaccine candidates are needed. The Contract Manufacturing Organization (CMO) to produce a new PRIMVAC clinical batch has been selected and activities have started. The GMP batch release is expected in Q4 2024 – January 2025. The manufacturing process for the PAMVAC-cVLP vaccine candidate has been optimised and is ready for transfer to the selected CMO for the manufacturing of the clinical batch. Planning of the clinical trial is ongoing.
In the context of the eHealth activities, the mobile application to monitor pregnancy outcomes has been selected and adapted for use in this project. Its feasibility has been confirmed. The EVAPREAP research study for the creation of electronic pregnancy registers and evaluation of the selected mobile application has started at the four African sites: FORS (Benin), GRAS (Burkina Faso), KHRC (Ghana) and MUST (Malawi).
The protocol and all other relevant documents for the cost-effectiveness study to be conducted in Malawi have been finalized and approved by the national and district health authorities and ethics committees. The PMVAC-CEACS study is expected to start in Q1 2024.
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 has been selected and adapted for use in this project. Its feasibility has been confirmed. The EVAPREAP research study for the creation of electronic pregnancy registers and evaluation of the selected mobile application has started at the four African sites: FORS (Benin), GRAS (Burkina Faso), KHRC (Ghana) and MUST (Malawi).
The protocol and all other relevant documents for the cost-effectiveness study to be conducted in Malawi have been finalized and approved by the national and district health authorities and ethics committees. The PMVAC-CEACS study is expected to start in Q1 2024.
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 provide support to front line health care workers and patients to ensure uptake and continued access to essential maternal and neonatal care services through responsive customized needs of patients in view of routine care packages.
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 provide support to front line health care workers and patients to ensure uptake and continued access to essential maternal and neonatal care services through responsive customized needs of patients in view of routine care packages.
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.