Despite successes in malaria control over the past several decades, over 436,000 people still die from malaria annually and the 2018 World Malaria Report estimates 219 million cases of malaria in 2017. Malaria control programs face several challenges including drug and insecticide resistance and the need for sustained investment to maintain gains in malaria control. The development of a safe, effective, and durable malaria vaccine would provide an additional tool for global malaria control and elimination programs.
The RTS,S/AS01 (Mosquirix) vaccine, the only malaria vaccine evaluated in a phase III clinical trial, demonstrated vaccine efficacy of approximately 40% in children aged 5-17 months against clinical malaria. The RTS,S/AS01 vaccine is currently entering advanced field trials under the malaria vaccine implementation program (MVIP) in Ghana, Kenya, and Malawi. While the RTS,S/AS01 vaccine showed a significant reduction in malaria cases in areas of high malaria burden in the phase III trial, the vaccine does not reach the World Health Organization (WHO) goal of a malaria vaccine that provides at least 75% protective efficacy against clinical malaria.
There are other vaccine candidates under development with some initial promising results; however, in their current form they are also unlikely to meet the WHO goal stated above. For these reasons the United States Agency for International Development (USAID) supports the development of a “next-generation” malaria vaccine that demonstrates a high level of protective efficacy and durability as envisioned by the WHO and other global partners.
USAID initiated a Malaria Vaccine Development Program (MVDP) in the 1960s in response to the end of the first malaria eradication program with the goal of accelerating the development of efficacious, durable, and affordable vaccines for use in malaria control programs in endemic areas of the developing world. Several milestones in the malaria vaccine development pathway were achieved with support from the MVDP, including malaria parasite culture, early development and clinical evaluation of circumsporozoite protein (CSP) and blood stage vaccines, and the first field trials of blood stage vaccines in East and West Africa. The USAID MVDP’s investments have historically been through interagency agreements with U.S. government partners, including the Walter Reed Army Institute of Research (WRAIR), the Naval Medicine Research Center (NMRC), and the National Institute of Allergy and Infectious Diseases (NIAID).
The USAID MVDP’s investments have also included the non-governmental / private sector including a cooperative agreement with PATH Malaria Vaccine Initiative (MVI) (2004-2014) and a contract with Leidos, Inc (2015-2020).
The USAID MVDP’s research and development (R&D) portfolio currently includes vaccine development efforts pre-erythrocytic (sporozoite and liver) stage parasites, and erythrocytic (blood) stage parasites. Presently, USAID supports research toward an improved CSP vaccine by evaluating various vaccine display platforms, including a CSP virus like particle (VLP) containing helper T cell epitopes of diverse parasite strains and human leukocyte antigen (HLA) type reactivity and enhanced B cell epitopes.
The USAID MVDP is also currently supporting the evaluation of a full-length CSP vaccine in a clinical trial. USAID has invested in liver stage vaccine efforts by NMRC and Oxford University to evaluate antigens expressed in the liver stage using a DNA-prime, chimpanzee adenovirus boost approach in a controlled human malaria infection trial. USAID also currently supports preclinical studies to evaluate additional potential highly conserved liver stage candidate antigens containing both CD4 and CD8 epitopes recognized by a broad repertoire of HLAs. USAID recently supported the Oxford University early stage clinical trial of the RH5 recombinant protein blood stage vaccine. Additionally, USAID supports preclinical studies of other blood stage antigens, including RH5 complex proteins, to build evidence sufficient to move forward along the vaccine development pipeline with these antigens.
USAID is seeking to enhance malaria vaccine investments through a collaborative design process. The goal of USAID’s Malaria Vaccine Development Program (MVDP) is to demonstrate the proof of concept of a vaccine to reduce morbidity and mortality due to malaria caused by infection with Plasmodium falciparum. Target malaria vaccine end characteristics will include at least 75% efficacy and evidence of affordability.
USAID intends to support efforts towards vaccines that have the potential to directly protect recipients against disease caused by P. falciparum such as vaccines that target the pre-erythrocytic (sporozoite and liver stage) and erythrocytic stages of the life cycle.
Expressions of Interest (EOI) are sought for novel and innovative approaches to malaria vaccine development that would encompass preclinical development through proof of principle clinical studies to motivate advanced development of a deployable, effective malaria vaccine.
Additional details are available via Funding Opportunity Number: GH-BAA-2018-ADDENDUM03.
 World Malaria Report 2018. Geneva: World Health Organization. 2018. Available from: https://www.who.int/malaria/publications/world-malaria-report-2018/en/
 RTS,S Clinical Trials Partnership. (2015). Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet, 386(9988),31-45.
 Malaria Vaccine Funders Group. Malaria Vaccine Technology Roadmap. 2013. Available from: http://www.euvaccine.eu/sites/default/files/uploads/Files/2-TRM_Update.pdf