Malaria
Research on malaria vaccines

Malaria vaccines have been another goal of research. The first promising studies demonstrating the potential for a malaria vaccine were performed in 1967 by immunising mice with live, radiation- attenuated sporozoites, which provided significant protection to the mice upon subsequent injection with normal, viable sporozoites. Since the 1970s, there has been considerable progress in developing similar vaccination strategies for humans.

In 2013, WHO and the malaria vaccine funders group set a goal to develop vaccines designed to interrupt malaria transmission with malaria eradication's long-term goal. The first vaccine, called RTS,S, was approved by European regulators in 2015. As of 2023, two malaria vaccines have been licensed for use. Other approaches to combat malaria may require investing more in research and greater primary health care. Continuing surveillance will also be important to prevent the return of malaria in countries where the disease has been eliminated.

As of 2019 it is undergoing pilot trials in 3 sub-Saharan African countries—Ghana, Kenya and Malawi—as part of the WHO's Malaria Vaccine Implementation Programme (MVIP).

Immunity (or, more accurately, tolerance) to P. falciparum malaria does occur naturally, but only in response to years of repeated infection. An individual can be protected from a P. falciparum infection if they receive about a thousand bites from mosquitoes that carry a version of the parasite rendered non-infective by a dose of X-ray irradiation. The highly polymorphic nature of many P. falciparum proteins results in significant challenges to vaccine design. Vaccine candidates that target antigens on gametes, zygotes, or ookinetes in the mosquito midgut aim to block the transmission of malaria. These transmission-blocking vaccines induce antibodies in the human blood; when a mosquito takes a blood meal from a protected individual, these antibodies prevent the parasite from completing its development in the mosquito. Other vaccine candidates, targeting the blood-stage of the parasite's life cycle, have been inadequate on their own. For example, SPf66 was tested extensively in areas where the disease was common in the 1990s, but trials showed it to be insufficiently effective.

As of 2020, the RTS,S vaccine has been shown to reduce the risk of malaria by about 40% in children in Africa. A preprint study of the R21 vaccine has shown 77% vaccine efficacy.

In 2021, researchers from the University of Oxford reported findings from a Phase IIb trial of a candidate malaria vaccine, R21/Matrix-M, which demonstrated efficacy of 77% over 12-months of follow-up. This vaccine is the first to meet the World Health Organization 's Malaria Vaccine Technology Roadmap goal of a vaccine with at least 75% efficacy.

Germany-based BioNTECH SE is developing an mRNA-based malaria vaccine BN165 which has recently initiated a Phase 1 study in December 2022. The vaccine, based on the circumsporozite protein (CSP) is being tested in adults aged 18–55 yrs at 3 dose levels to select a safe and tolerable dose of a three-dose schedule. Unlike GSK's RTS,S (AS01) and Serum Institute of India's R21/MatrixM, BNT-165 is being studied in adult age groups meaning it could be developed for Western travelers as well as those living in endemic countries. For the travelers profile, a recent commercial assessment forecast potential gross revenues of BNT-165 at $479m (2030) 5-yrs post launch, POS-adjusted revenues.
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