Despite significant progress achieved in the past years, malaria remains a major cause of morbidity and mortality, especially in children in sub-Saharan Africa. A safe and effective vaccine would represent a game changer in the fight against this disease.
The malaria parasites are transmitted through the bite of an infected female Anopheles mosquito into humans, and it has different life stages (pre-erythrocytic, liver, blood and sexual stages). When developing vaccines, different stages of the parasite’s life cycle can be targeted.
One of the vaccine candidates being pursued, targets the blood stage and is based on the Apical Membrane Antigen 1 (AMA1) of the malaria-causing parasite, Plasmodium falciparum (Pf). The PfAMA1 protein is essential for the malaria parasite to be able to invade human red blood cells and it shows considerable sequence diversity across different parasite strains.
The PfAMA1 Diversity Covering (DiCo) vaccine candidate was designed using a novel approach to overcome the polymorphisms present in the PfAMA1 protein. Three PfAMA1 DiCo proteins have been designed and selected to be used in combination, as a vaccine candidate with the objectives to induce a broad response to the multitude of strains found in the field, and to protect specific target groups, e.g., infants from endemic areas and travellers, against severe disease.
For first-in-human evaluation of the vaccine, EVI developed a phase I clinical trial fast-track strategy based on a staggered multi-centre phase Ia/b clinical trial including both malaria-naive and malaria-exposed adults. The results from this clinical trial demonstrated that the PfAMA1 DiCo vaccine candidate, formulated with either of two adjuvants (Alhydrogel® or GLA-SE), is safe and well-tolerated. Importantly, it was also shown to induce antibody responses against multiple strains of the malaria parasite in adults that never contracted the disease. The antibody levels induced by the vaccine were similar to the ones found in adults that have been naturally infected with malaria.
However, when testing the best vaccine formulation (GLA-SE adjuvanted vaccine) in endemic populations of Burkina Faso, the volunteers did not develop increased vaccine-induced antibody responses.
This study not only illustrates the value of phase I fast-track strategy developed by EVI, but also paves the way for future exploration of the combination of PfAMA1 DiCo with a potent adjuvant as a stand-alone vaccine or in combination with other vaccine candidates.
Read the full npj Vaccines article here.
Original Article: Remarque, E.J., Faber, B.W., Rodriguez Garcia, R. et al. Accelerated phase Ia/b evaluation of the malaria vaccine candidate PfAMA1 DiCo demonstrates broadening of humoral immune responses. npj Vaccines 6, 55 (2021). https://doi.org/10.1038/s41541-021-00319-2
Today on 20th of August, on #WorldMosquitoDay alongside our partners we will continue working toward eradicating this deadly mosquito-borne disease.