Malaria vaccine

Malaria is a serious infectious disease spread by mosquitoes. In 2022, it affected an estimated 249 million people across 85 endemic countries. This disease caused 608,000 deaths in that same year.

To fight this, scientists developed vaccines to protect vulnerable populations. These vaccines are now included on the World Health Organization's List of Essential Medicines. They aim to stop the malaria parasite before it can cause severe illness.

The first approved vaccine is known as RTS,S, or by its brand name, Mosquirix. This is a recombinant vaccine, meaning it is engineered using specific genetic material. It uses the circumsporozoite protein, or CSP antigen, from the pre-erythrocytic stage of the parasite.

The vaccine works by inducing high antibody titers in the body. These antibodies block the parasite from invading the hepatocytes, which are cells in the liver. It also triggers a cellular response to help destroy any infected liver cells.

To make the vaccine more potent, scientists fused the CSP protein with a surface antigen from the hepatitis B virus. This process helped improve its immunogenicity, which is the ability to provoke an immune response. The vaccine was tested as an emulsion of oil in water. It included adjuvants like monophosphoryl A and QS21 to boost the immune system. In trials, this helped 7 out of 8 volunteers stay protected when challenged with the parasite.

Using the RTS,S vaccine requires a specific schedule for infants. Children need at least three doses by the age of two. A fourth booster dose can extend protection for another one to two years. Clinical trials showed that the vaccine reduces hospital admissions from severe malaria by about 30%. However, the vaccine's effectiveness can wane over time. Without a booster, the protection against severe malaria becomes negligible.

A newer and more effective option is the R21/Matrix-M vaccine. It is the first vaccine to meet the World Health Organization's goal of at least 75% efficacy. Initial trials showed a 77% efficacy rate. It also produces significantly higher antibody levels than the RTS,S vaccine. This vaccine was developed through a large collaboration. Partners included the University of Oxford's Jenner Institute, the Kenya Medical Research Institute, and the Serum Institute of India.

The R21 vaccine also uses the CSP antigen but at a higher proportion. It uses a similar recombinant structure to RTS,S but contains no excess hepatitis B surface antigen. It also utilizes the Matrix-M adjuvant. In a phase III trial involving 4,800 children, the vaccine showed 74% efficacy against severe malaria. Recent data from 2024 showed 78% efficacy in children aged 5 to 17 months. Ghana approved this vaccine in April 2023 for children aged five months to three years. Nigeria also provided provisional approval.

Many different types of vaccines have been studied throughout history. Some researchers used a synthetic peptide-based vaccine called SPf66 in the 1990s. However, it was not effective enough in Africa and was abandoned. Other candidates, like the NYVAC-Pf7, tried to target seven different genes from various life stages of the parasite. While some showed promise in monkeys, human trials resulted in poor antibody responses. There is also the PfSPZ vaccine, which uses radiation-attenuated sporozoites. This candidate has shown over 80% protection in trials, but it must be stored in liquid nitrogen.

Scientists are now looking toward the future of malaria prevention. They are developing a second-generation vaccine called RH5.1/Matrix-M. This candidate targets the erythrocytic stage, which is the stage where the parasite lives in the blood. Researchers hope to combine this with the R21 vaccine. By targeting different parts of the parasite's life cycle, they hope to create even stronger protection.

This ongoing work could eventually lead to much better control of the disease.