AAHI Collaborates to Protect Against Malaria

AAHI’s immune-enhancing adjuvant formulation platform enables development of cost-effective malaria vaccines that are equitably accessible in areas of the world most burdened by the disease, such as Uganda, Mozambique, Tanzania, India, and Brazil.

Malaria is a parasitic disease carried by female Anopheles mosquitoes native to Africa. According to the latest World Malaria Report, malaria has claimed over 600,000 lives with over 200 million people infected in 2021 alone. The lifecycle of the malaria parasite makes the disease difficult to target, as the parasite changes and matures.  Vaccine development must target one of the three phases of the malaria parasite lifecycle: liver cell infection (pre-erythrocytic vaccines), blood cell infection (blood-stage vaccines), and malaria sporozoites in mosquitos (transmission blocking vaccines). To further complicate matters, there are five different malaria (Plasmodium) parasite species.  Vaccine development has focused on two of these species - P. falciparum and P. vivax --which pose the largest threat to humans, especially pregnant women and children under 5 years, who accounted for 80% of all malaria deaths in Africa.

In 2021, the World Health Organization approved the first malaria vaccine, GSK’s Mosquirix®, for use in young children up to three years old. Mosquirix® is a pre-erythrocytic vaccine that targets the P. falciparum strain of malaria and requires a four-dose regimen. The vaccine is also referred to as RTS,S/AS01 because the two components are the RTS,S protein antigen and GSK’s AS01 saponin adjuvant formulation, which provides a boost to the body’s immune defense against malaria.

QS-21 is an important weapon in the battle against malaria. GSK's AS01 adjuvant formulation used in Mosquirix combines a TLR4 agonist, MPL, with a saponin, QS-21. The combination works to stimulate a robust immune response to protect against malaria. AAHI's own saponin adjuvant formulation, GLA-LSQ, combines a synthetic TLR4 agonist, GLA, with QS-21. AAHI's GLA-LSQ is being clinically evaluated in several malaria vaccine candidates. QS-21 is derived from the bark of an endangered Chilean soapbark tree, Quillaja saponaria, and increasing demand has put increasing pressure on ability to source the already scarce raw vaccine material.  Researchers continue to explore QS-21 sourcing alternatives and have recently identified a synthetic pathway by which saponin can be produced in the tree’s leaves (not just the bark), for easier and more sustainable harvesting. AAHI has innovated its own high-purity, high yield process for   extracting QS-21, to maximize yield from scarce raw material.

While Mosquirix was a significant contribution to global health, there is still an unmet need for a malaria vaccine that is available and accessible to all populations, including adults, seniors, and pregnant women. Malaria is on the rise; climate change has expanded mosquito ranges and affected seasonal mosquito behavior in Africa, disrupting attempts to curb and control the mosquito population. There is a cure for malaria, but the series of antibiotics is expensive and out of reach in low-and middle-income countries, where malaria is most common.

AAHI partners with vaccine developers around the world to use AAHI's GLA-LSQ (TLR4 agonist and saponin) and GLA-SE (squalene emulsion) adjuvant formulations, with malaria proteins that target P. falciparum, placental malaria, and P. vivax. These vaccine candidates all target different stages of the parasite’s lifecycle and each is currently advancing through clinical trials.

Of the eight malaria vaccine candidates that include AAHI’s adjuvant formulations technology and are advancing to clinical trials, six  target P. falciparum, the deadliest and most prevalent strain of malaria. 

AAHI partners with research institutes and government agencies, including the Institut National de la Santé Et de la Recherche Médicale (INSERM, NCT02014727), the European Vaccine Initiative (EVI, NCT01949909), and the U.S. Army Medical Research and Materiel Command and United States Agency for International Development (USAMRMC and USAID, NCT01540474) to provide AAHI’s GLA-SE adjuvant formulation for combination with their malaria protein antigens that target blood-stage malaria. AAHI is also partnered with a small biotech, Sumaya, to develop a dual-stage malaria vaccine with GLA-SE (NCT05644067) This vaccine candidate will be evaluated in Phase 1 clinical trials in Tanzania this year.

The National Institute of Allergy and Infectious Diseases (NIAID) has tested a malaria vaccine combining AAHI’s saponin based adjuvant formulation, GLA-LSQ, with a recombinant circumsporozoite protein (CSP) antigen in Phase 1 clinical trials, which included a Controlled Human Malaria Infection challenge study (NCT03589794). The University of Florida is also evaluating a malaria vaccine candidate, AnAPN1, that uses GLA-LSQ but targets the transmission-blocking phase of the parasite’s life-cycle. AnAPN1 is expected soon to enter Phase 1 clinical trials in Gabon with the support of the Global Health Innovative Technology (GHIT) Fund.

P. falciparum in pregnant women can easily develop into placental malaria, jeopardizing development of the child. AAHI is partnered with the European Vaccine Initiative (EVI) to support development of two placental malaria vaccine candidates that incorporate AAHI’s adjuvant formulations.  One of these candidates, PAMVAC, has been tested in alternative formulations – one using GLA-SE and one using GLA-LSQ - in a Phase 1 clinical trial in malaria-exposed adult pregnant women (NCT02647489). The other placental malaria vaccine candidate is PRIMVAC, using GLA-SE, and is also developed with INSERM (NCT02658253).

AAHI is dedicated to developing affordable and easily accessible vaccines to protect all parts of the world, including those with the most malaria-carrying mosquitos. We are grateful to our partners for working toward eradicating malaria -- making it possible to deliver zero malaria through investment, innovation, and implementation. Our scientists will continue to provide platforms and products to address health inequities and ensure a healthy life for people in all areas of the world.

Learn more about AAHI's efforts to provide protection against other neglected tropical diseases.