Protect Against 

Malaria

 AAHI: 

  • Supports the development of eight different malaria vaccine candidates using our immune-enhancing adjuvant formulations to enable them to be cost-effective and equitably accessible in areas of the world most burdened by disease, such as Uganda, Mozambique, and Brazil. All eight candidates are advancing to human clinical trials. 

Malaria is a parasitic disease carried by female Anopheles mosquitos native to Africa. The life-threatening disease is mostly found in tropical countries where mosquitoes thrive. 

There are five Plasmodium parasite species that cause malaria, two of which are the greatest threat, especially to pregnant women and children under 5 years-old - P. falciparum and P. vivax.


The other three malaria species are:  

  1. P. malariae
  2. P. ovale
  3. P. knowlesi

The most common symptoms of malaria are fever, headache, and chills, which occur during the first two weeks of getting bitten by a mosquito carrying the disease.


Symptoms are mild for some people and if detected early on, treatment can prevent severe disease. But people with weaker immune symptoms, including young children, pregnant women, and immunocompromised individuals, can experience severe symptoms. 

When left untreated, severe symptoms will manifest in extreme fatigue, impaired consciousness, ongoing convulsions, jaundice, abnormal bleeding, difficulty breathing, and ultimately, death. 

A TREATABLE DISEASE

There are many treatments available for malaria depending on the type of malaria and the patient, specifically their age, weight, and whether they are pregnant. The series of antibiotics are expensive and out of reach in low-and middle-income countries, where malaria is most common.

The available treatments include Artemisinin-based combination therapy medicines, chloroquine, and primaquine. Depending on the severity of disease, patients may need to go to a hospital for injectable medicines from trained health personnel, which is difficult to access in Africa where the deadlies species of malaria is most prevalent.

In 2021, the World Health Organization (WHO) approved the first malaria vaccine, GSK's Mosquirix (R), for use in young children up to three years old. 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. 

This year, the WHO recommended a new vaccine, R21/Matrix-M, to prevent malaria in children. The vaccine combines the R21 protein with Novavax's Matrix-M saponin adjuvant formulation.

The global malaria disease burden disproportionately effects Africa, the continent the Anopheles mosquito species are native to. 


According to the WHO, four African countries accounted for over half of all malaria deaths: Nigeria, the Democratic Republic of the Congo, United Republic of Tanzania, and Niger. 

CURRENT VACCINES USE UNSTAINABLE RAW VACCINE MATERIAL - SAPONIN

QS-21 is an important weapon in the battle against malaria. The only two vaccines on the market to prevent malaria contain QS-21, a saponin derived from the bark of a rare Chilean soapbark tree, Quillaja saponaria, and increasing demand has put increasing pressure on ability to source the already scarce raw vaccine material.

A PARASITE THAT IS DIFFICULT TO TARGET

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: 

  1. Liver cell infection (pre-erythrocytic vaccines)
  2. Blood cell infection (blood-stage vaccines)
  3. Malaria sporozoites in mosquitos (transmission blocking vaccines)

Mosquirix is a pre-erythrocytic vaccine that targets the P. falciparum strain of malaria and requires a four-dose regimen. R21/Matrix-M is also a pre-erythrocytic vaccine that requires a three-dose regimen.

While Mosquirix and R21/Matrix-M were 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. 

CONTENTS

3. What AAHI Does About It

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. 

A SUSTAINABLE SAPONIN SOLUTION

AAHI's own saponin adjuvant formulation, GLA-LSQ is being clinically evaluated in several malaria vaccine candidates. AAHI 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.

Of the eight malaria vaccine candidates that include AAHI's adjuvant formulation 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).

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